Coagulation factor xii ( fxii ) is activated on contact with various biologic surfaces , including subendothelial tissues and lipoprotein particles .
Coagulation factor xii ( hageman factor , fxii ) is a serine protease secreted by the liver and activated by negative charged surfaces to play roles in fibrinolysis , coagulation , and inflammation .
Coagulation factor xii ( fxii ) activity , activated fxii , distribution of fxii c46t gene polymorphism and coronary risk .
Factor xii was subsequently added , and the generation of renin at 37 degrees c was observed after complete factor xii-high mol wt kininogen-mediated activation of prekallikrein induced by dextran sulfate .
Factor xii interacts with the multiprotein assembly of urokinase plasminogen activator receptor , gc1qr , and cytokeratin 1 on endothelial cell membranes .
Factor xii levels and kallikrein-like activities ( a measure of contact system activation ) were followed before , during , and one day after cardiopulmonary bypass in 20 patients .
Factor xii , prekallikrein and high molecular weight kininogen could be activated through the dilution of red cell concentrates during the priming and contact with the circuits .
Factor xii binds primarily to cell surface u-par ( urokinase plasminogen activator receptor ) ; hk binds to gc1qr via its light chain ( domain 5 ) and to cytokeratin 1 by its heavy chain ( domain 3 ) and , to a lesser degree , by its light chain .
Factor xii ( fxii ) is a liver-specific zymogen involved in the regulation of hemostasis , particularly in the activation of fibrinolysis .
Factor xii ( fxii , plasma concentration 375 nm ) is a critical member of the plasma contact activation system and is the zymogen form of fxiia , a serine protease involved in intrinsic coagulation , complement activation , activation of factor vii , and generation of the vasoactive peptide bradykinin .
Factor xii in the plasma preparation was activated to unfragmented factor xiia by adsorption to kaolin , and assayed as prekallikrein activator ( pka ) .
Factor xii not only has an important function in the initiation of the intrinsic pathway of the coagulation cascade , but it also plays a significant role in complement activation , kinin generation , and fibrinolysis .
Factor xii has long been implicated in the intrinsic pathway of fibrinolysis , but the mechanism by which it triggers plasminogen activation and targets fibrinolysis has not been established .
Factor xii has been assayed as kaolin-activated prekallikrein activator in rat citrated plasma pretreated with acetone ( briseid et al 1978 & 1979 ; briseid & berstad 1979 ) .
Factor xii , ppk and hmwk are necessary for full activation .
Factor xii is activated by collagen , i.e. , whenever the vascular endothelium is injured , and to a lesser extent also by "activated" blood platelets .
Factor xii was assayed in acetone-treated and kaolin-activated human citrated plasma ( total plasma dilution 10 + 03 v/v during activation with kaolin , 18 mg/ml incubate ) .
Factor xii incubated in the absence of moab f1 was hardly activated by kallikrein , whereas in the presence of moab f1 , but not in that of a control moab , the rate of factor xii activation by kallikrein was promoted at least 60-fold .
Factor xii was assayed as prekallikrein activator ( pka ) activated with kaolin at 0 degrees , and kininogen fractions were estimated through the release of kinin caused by plasma kallikrein or hog pancreas kallikrein ( hpk ) .
Factor xii and other plasma proteases first activate small amounts of c1s ; the resulting c1 esterase then activates the bulk of c1s .
Factor xii does not initiate prekallikrein activation on endothelial cells .
Factor xii ( fxii ) autoactivates by contact with a variety of artificial or biologic negatively charged surfaces ( contact activation ) , resulting in blood coagulation and activation of the inflammatory kallikrein-kinin and complement systems .
Factor xii activation and inhibition in inflammation .
Factor xii plays a central role in the intrinsic activation of fibrinolysis and consequently the defective intrinsic fibrinolytic activity detected in the present case casts some doubt on its role in the increased vulnerability to thrombotic accident .
Factor xii activation was less on the alumina films than on the segmented polyurethane .
Factor xii was activated by misfolded protein aggregates that formed by denaturation or by surface adsorption , which specifically led to the activation of the kallikrein-kinin system without inducing coagulation .
Factor xii deficiency is not associated with bleeding , which suggests that another mechanism for factor xi activation exists in_vivo. a revised model of coagulation is proposed in which factor xi is activated by thrombin .
Factor xii autoactivation was investigated using dextran sulfate as a soluble activating surface , and the significance of aggregation and the nature of the conformational change were examined by ultraviolet difference spectroscopy , fluorescence and circular dichroism .
Blood coagulation factor xii ( fxii , hageman factor ) is a plasma serine protease which is autoactivated following contact with negatively charged surfaces in a reaction involving plasma kallikrein and high-molecular-weight kininogen ( contact phase activation ) .
Activated coagulation factor xii and kallikrein formation on the surfaces and in the plasma were studied using a kallikrein-specific colorimetric assay. 3-mercaptopropionic acid indicated contact activation of coagulation but l-cysteine did not .
Human coagulation factor xii ( fxii ) , a serine protease synthesized in liver and active in plasma , is involved in a wide variety of functions , including blood coagulation , fibrinolysis , bradykinin and complement activation .
Human blood coagulation factor xii ( fxii ; 80 kda ) contains a c-terminal serine protease zymogen domain , which becomes activated upon contacting a negative surface .
Plasma factor xii activity , activated protein c resistance , factor v leiden mutation analysis , protein c , protein s , antithrombin iii , karyotyping , and anticardiolipin antibodies .
The factor xii and prekallikrein activity are significantly increased 151.9% and 112.4% respectively in the cold promoted activation positive plasmas ( cpa pos ) whereas the activity of c1-inhibitor is decreased , 76%. the quotient of the product of the c1-inhibitor and alpha 2-macroglobulin values divided by the product of the fxii and prekallikrein values is significantly lower in the cpa pos plasma 0.49 than in cpa neg plasma 0.96 ( p less than 005 ) .
[congenital factor xii deficiency :a rare cause of increased activated cephalin time]
Activated factor xii converts prekallikrein to kallikrein by limited proteolysis and two disulfide-linked chains designated kallikrein heavy chain ( mr = 52,000 ) and kallikrein light chains ( mr = 36,000 or 33,000 ) are formed .
Activated factor xii ( xiia ) , activated factor vii ( viia ) and factor vii coagulant activity ( viic ) were determined in non-treated and in treated ( cold-incubated ) citrated plasmas from women in late pregnancy and from norma volunteers .
Human factor xii was activated by limited proteolysis with trypsin , and the resulting beta-factor xiia ( mr = 30,000 ) was isolated by deae-sephacel column chromatography .
Activated factor xii was not associated with risk .
Thus factor xii is critical for activation to proceed .
Activated factor xii in rheumatoid arthritis .
Activated factor xii levels and factor xii 46c > t genotype in relation to coronary artery calcification in patients with type 1 diabetes and healthy subjects .
Whether factor xii ( fxii ) activity , its 46c > t polymorphism and activated fxii ( fxiia ) are associated with coronary heart disease ( chd ) remains to be determined .
Activated factor xii ( xiia ) is believed to participate in a number of pathophysiological processes including inflammation , thrombosis and fibrinolysis .
Activated factor xii type a predicts long-term mortality in patients admitted with chest pain .
Maximal factor xii activation in_vitro with ellagic acid levels the difference of clotting times again .
(i) factor xii , prekallikrein and contact system inhibitors were subnormal in 10/12 and activated factor xii raised in 11/12 patients at baseline , implying pre-existing contact pathway activation. ( ii ) no change occurred during haemofiltration in the intrinsic coagulation pathway factor or inhibitor levels. ( iii ) clotting of the filter circuit within the first 24 h occurred in 5/12 and was associated with low baseline levels of antithrombin iii and heparin co-factor ii .
Activated factor xii ( fxiia ) is involved in vascular injury and repair , participating in inflammation , thrombosis , and fibrinolysis .
Activated factor xii levels are dependent on factor xii 46c/t genotypes and factor xii zymogen levels , and are associated with vascular risk factors in patients and healthy subjects .
Although factor xii will bind to the intact platelet through gp ibalpha ( glycocalicin ) without activation , we now report that factor xiia ( 0 37 microm ) , but not factor xii zymogen , is required for the inhibition of thrombin-induced platelet aggregation .
When factor xii was adsorbed to kaolin it slowly became activated and converted prekallikrein to kallikrein .
Activated factor xii ( fxiia ) , the initiator of the contact activation system , has been shown to activate plasminogen in a purified system .
Activation of factor xii and prekallikrein with polysaccharide sulfates and sulfatides : comparison with kaolin-mediated activation .
Activation of factor xii in human plasma : protection by benzamidine of the cofactor function of high molecular weight kininogen .
Activation of factor xii by tobacco glycoprotein .
Activation of factor xii in rat plasma : protection by benzamidine of the cofactor function of high molecular weight kininogen .
Levels of factor xii were reduced in 2 patients who had single factor assays performed , consistent with activation of the kallikrein-kinin system .
The activated factor xii kit ( shield diagnostics ) has recently been commercially available , and the reference range was reported in the instruction manual .
Purified human factor xii zymogen was not activated by heparin through an autoactivation mechanism , but was activated in the presence of purified prekallikrein .
Association of factor xii in this conformation on the activating surface was suggested to be responsible for the autoactivation .
Studies on factor xii in porcine plasma : purification and its conversion to activated form by porcine plasma kallikrein .
Activation of factor xii in solution was equally well catalyzed by kallikrein and its light chain .
Activation of factor xii initiates coagulation by the intrinsic coagulation pathway and activates complement .
The stoichiometric factor xii concentration-effect curve obtained by diluting acetone-treated rat plasma with acetone-treated human factor xii deficient plasma showed that factor xii is present in functional excess , the concentration of hmwk deciding the extent of activation .
Activation of factor xii initiates activity in the plasma contact system , and we have identified factors ( negatively charged surfaces ) present in elevated concentrations in the plasma of patients who are asthmatic or allergic that can "prime" their plasma for the initiation and/or potentiation of factor xii activation .
Activation of factor xii in acetone-treated human plasma : significance of the functional state of plasma kallikrein for the extent of activation .
Activation of factor xii and prekallikrein with cholesterol sulfate .
The human factor xii gene codes for a serine proteinase synthesized in liver that activates both the coagulation and the fibrinolytic cascades .
However , factor xii was not activated and fibrinolysis was not increased .
Given that factor xii accelerates the interactions among cell surfaces and proteins of the contact activation cascade to generate bradykinin , binding of factor xii ( and the prekallikrein-hk complex ) may serve as a mechanism by which these proteins are concentrated locally to facilitate their interactions .
Thus , factor xii , prekallikrein , and hmw kininogen are essential components for optimal activation of prekallikrein .
Light chain-dependent factor xii activation in the presence of sulfatides , was optimal at ph 7.0 and was not affected by variation of the ionic strength .
Activation of factor xii by dextran sulfate : the basis for an assay of factor xii .
Inhibition of factor xii in septic baboons attenuates the activation of complement and fibrinolytic systems and reduces the release of interleukin-6 and neutrophil elastase .
Activation of factor xii in plasma from rats pretreated with tranexamic acid .inhibition of a plasmin-induced loss of the functional activity of high molecular weight kininogen .
Activation of factor xii and subsequent release of beta-xiia was brought about by the proteolytic action of co-adsorbed kallikrein .
Activation of factor xii and cleavage of high molecular weight kininogen during acute attacks in hereditary and acquired c1-inhibitor deficiencies .
Individuals with severe factor xii ( fxii ) deficiency may be prone to thromboembolic disease and this thrombophilic state may be due to insufficient contact activation dependent fibrinolysis .
When purified human blood coagulation factor xii ( hageman factor ) is incubated with sulfatides at 37 degrees c , activation of factor xii occurs as judged by the appearance of amidolytic activity towards the chromogenic substrate h-d-pro-phe-arg-p-nitroanilide .
Studies that compared factor xii surface binding to factor xii activation found that binding alone was insufficient to account for surface enhancement of the activation rate .
The activation of factor xii and prekallikrein by polysaccharide sulfates and sulfatides in the presence of high-molecular-weight ( hmw ) kininogen was studied , and compared with the kaolin-mediated activation reaction .
In_vivo activation of factor xii initiated pathways occur in septic shock , disseminated or localized intravascular coagulation , typhoid fever , polycythemia vera , hyperbetalipoproteinemia , coronary artery disease , nephrotic syndrome , transfusion reactions , hemodialysis and extracorporeal bypass .
Bismuth subgallate activates factor xii and therefore accelerates the coagulation cascade .
Bismuth subgallate activates factor xii ( hageman factor ) and , therefore , markedly accelerates the cascade of blood clotting .
Another 'potentiator' of factor xii activation was isolated from proteins adsorbed to aluminum hydroxide .
Functionally , this factor xii deficiency did not interfere with plg activation .
Pharmacological regulation of factor xii activation may be a new target to control pathological coagulation .
Hageman factor ( factor xii ) is activated by exposure to surfaces such as glass or by solutions of certain compounds , notably ellagic acid .
Measurement of activated factor xii in health and disease .
Rapid loss of factor xii and xi activity in ellagic acid-activated normal plasma : role of plasma inhibitors and implications for automated activated partial thromboplastin time recording .
The activation of factor xii occurs via fragmentation of this zymogen into a diverse spectrum of enzymatically potent molecular species .
It inhibited the activated coagulation factor xii ( fxiia ) by forming an inactive complex regardless of zn2+ mediation , and was named , yellowfin sole anticoagulant protein ( yap ) .
Differential binding of factor xii and activated factor xii to soluble and immobilized fibronectin--localization of the hep-1/fib-1 binding site for activated factor xii .
Analysis of the factor xii concentration dependence of initial activation rates revealed that zn ( ii ) , at levels that saturate the effect , accelerates kallikrein activation of factor xii by lowering km ( from 52 to 73 microm ) and raising kcat ( from 26 to 31 min-1 ) .
Hageman factor ( factor xii ) is a plasma proenzyme that , when activated by certain negatively charged agents , initiates clotting via the intrinsic pathway of thrombin formation .
A high activated factor xii was associated with increased chd risk , but low levels were not protective .
The activation of factor xii by plasma kallikrein ( reaction 1 ) and the activation of prekallikrein by factor xiia ( reaction 2 ) .
Surface-independent acceleration of factor xii activation by zinc ions .ii. direct binding and fluorescence studies .
Hageman factor ( factor xii ) , high-molecular-weight kininogen ( hmwk ) and prekallikrein ( pk ) form a complex on the surface of this activator , and bradykinin is released from hmwk by the action of kallikrein converted from pk .
Surface activation of factor xii ( hageman factor ) --critical role of high molecular weight kininogen and another potentiator ) .
Misfolded proteins activate factor xii in humans , leading to kallikrein formation without initiating coagulation .
In addition , factor xii activation induces disordered hemostasis , which is related to increased fibrinolysis and a possible disturbance in platelet function .
Inhibition of activated factor xii by antithrombin-heparin cofactor .
The autoactivation of factor xii ( hageman factor ) induced by low-mr heparin and dextran sulphate .the effect of the mr of the activating polyanion .
The cell-bound activated factor xii was also able to activate prekallikrein .
At prekallikrein and factor xii levels equal to those in plasma , reciprocal activation is approximately 2000-fold more rapid than autoactivation .
Surface-independent acceleration of factor xii activation by zinc ions. i. kinetic characterization of the metal ion rate enhancement .
The activation of factor xii and the contact system by heparin in plasma anticoagulated with citrate or with hirudin ( not chelating ions ) was examined by the cleavage of 125i-labeled factor xii and high molecular weight kininogen ( hk ) .
Maximal activation of factor xii with kallikrein in the presence of moab f1 was reached within 1 hour .
Binding of activated factor xii to endothelial cells affects its inactivation by the c1-esterase inhibitor .
Targeted deletion of murine coagulation factor xii gene-a model for contact phase activation in_vivo .
The activation of factor xii by the proteases factor xiia and kallikrein is known to be greatly enhanced by certain negatively charged surfaces .
Levels of activated factor xii ( fxiia ) and vii ( fviia ) were determined in 100 women with uneventful pregnancies .
Activation of zymogen factor xii to its active enzymatic forms by kallikrein resulted in factor xiia and factor xiif as observed with factor xii purified by other procedures .
When activated , factor xii ( fxii ) has been shown to play a role in a series of proteolytic cascades including systems as the fibrinolytic , the coagulation , the kallikrein-kinin and the complement .
This effectively activates factor xii and releases platelet factor 3 , thereby markedly shortening the clotting time .
Sulfatides greatly stimulate factor xii activation .
Addition of inhibitors to factor xii fragments ( corn hageman factor inhibitor , chfi ) or to activated factor xii ( cytochrome-c ) inhibited in a concentration-dependent way the cold-promoted activation of factor vii and the shortening of the pt .
The genetic relationships between the kringle domains of human plasminogen , prothrombin , tissue plasminogen activator , urokinase , and coagulation factor xii .
Glucocorticoids prevent activation of factor xii by endotoxin in_vivo and decrease production of tissue factor by macrophages .
No further activation of factor xii was obtained at 0.80 microgram/ml .
Urokinase-type plasminogen activator , factor xii , protein c , trypsinogen iv , and a protease that we refer to as membrane-type serine protease 1 ( mt-sp1 ) .
Contact activation of blood factor xii ( fxii , hageman factor ) in neat-buffer solution is shown not to be specific for anionic hydrophilic procoagulants as proposed by the accepted biochemistry of surface activation .
With kaolin , activated factor xii ( xii(a) ) was the apparent principal activator .
Alpha 2m-kk potentiated the factor xii activation on kaolin and the kallikrein production in a dextran-sulfate-mediated assay .
The ph optimum of factor xii activation by kallikrein in the presence of sulfatides was shifted to ph 6.3 , and the reaction became highly ionic-strength-dependent .
Two different heparin surfaces , structurally closely related and of similar negative charge characteristics , were compared with regard to adsorption and activation of coagulation factor xii ( fxii ) .
This inhibitor protein , referred to as chfi ( for the corn inhibitor of activated hageman factor ) or as the popcorn inhibitor , is an important tool for specific inhibition of human activated hageman factor ( activated forms of coagulation factor xii ) and has been well characterized as isolated from corn seeds .
In dextran sulfate-activated plasma , neurotropin inhibited the formation of bk , the cleavage of high molecular weight kininogen ( hk ) and the formation of kallikrein-c1 inhibitor and activated coagulation factor xii ( fxiia ) -c1 inhibitor complexes .
Fchl patients exhibited significantly higher thrombin-antithrombin complex ( tat ) , activated coagulation factor xii ( f xiia ) , von willebrand factor ( vwf ) , plasminogen activator inhibitor-1 ( pai-1 ) and tissue derived plasminogen activator ( t-pa ) values in comparison to controls .
The initial step in activation of the plasma kinin system is activation of hageman factor ( coagulation factor xii ) and/or plasma prekallikrein .
Fibronectin binds to fibrin and collagen reversibly and crosslinks to these filamentous proteins catalyzed by the activated blood coagulation factor xii ( plasma transglutaminase ) .
Contact activation of the intrinsic pathway of the blood coagulation cascade is initiated when a procoagulant material interacts with coagulation factor xii , ( fxii ) yielding a proteolytic enzyme fxiia .
Sulfatide ( galactosylceramide i3 -sulfate ) has been reported to activate blood coagulation factor xii ( hageman factor ) , which suggests that it exhibits coagulant activity ( fujikama et al , 1980 biochemistry 19 , 1322-1330 ) however , sulfatide administered into animals as a bolus shot without subsequent thrombus formation , prolonged conventional clotting times and bleeding time ( hara et al , 1996 glycoconjugate j 13 , 187-194 ) .
Beta 2 glycoprotein-i inhibits factor xii activation on triglyceride rich lipoproteins : the effect of antibodies from plasma of patients with antiphospholipid syndrome .
Expression , refolding , and activation of the catalytic domain of human blood coagulation factor xii .
The ability of various mixtures of purified human hageman factor ( coagulation factor xii ) , hmrk , prekallikrein , and kaolin to activate coagulation factor xi was determined with factor xia ( activated factor xi ) clotting assays .
The monomeric form of factor xii tenri , like normal factor xii , was degraded into 2 major fragments with molecular weights of approximately 45 kda and 30 kda following mixing with activated partial-thromboplastin-time measuring reagent ( cephalin and ellagic acid ) , whereas the factor xii tenri that formed the complexes was not .
When the concentration of factor xii was reduced to only several molecules per vesicle , the autoactivation rate dropped very low whereas kallikrein activation held relatively constant .
Moab f1-induced activation of factor xii in this purified system was not dependent on the presence of high-molecular-weight kininogen ( hk ) , in contrast to the activation of the contact system in plasma by moab f1 .
Changes of plasma activated factor xii type a ( xiiaa ) concentrations following percutaneous coronary intervention ( pci ) .
Potent blood pressure raising effects of activated coagulation factor xii .
Continual decreases observed in factor xii and prekallikrein indicate that the coagulofibrinolytic activation occurring during lvad treatment is presumably the result of contact activation of these factors due to interaction of blood with the internal surface of the lvad .
C1inh is the sole inhibitor of the activated proteases c1r and c1s , and is the major regulator of activated coagulation factor xii and plasma kallikrein , which limits the generation of the vasoactive peptide bradykinin .
Also the activation of factor xii to factor xiia , assayed as prekallikrein activator , was strongly inhibited in ac-treated rats .
Prothrombin activation fragment ( f12 ) is increased in pregnant patients with antiphospholipid antibodies .
Sulfosphingolipids ( sulfogalactosylceramide ) may be involved in sodium transport , interaction of opiates with their receptors , activation of oxygen radical generating system , and blood coagulation factor xii .
Surface-dependent activation of human factor xii ( hageman factor ) by kallikrein and its light chain .
Formed kallikrein then activates factor xii ( fxii ) for amplification of its activation and single chain urokinase .
In the physiological route , gluey particles with negative charges can activate intrinsic coagulation systems by activating the blood coagulation factor xii after fhf dissolution .
The relationship of activated factor xii ( fxiia ) and fxii 46c > t genotype to coronary atherosclerosis and endothelial function was examined in 192 randomly sampled subjects from the general population and 190 type 1 diabetic subjects ( mean age 38+/-4 years ) .
Some exons of this gene showed significant similarities to those of coagulation factor xii , tissue-type plasminogen activator , and urokinase genes in nucleotide length and in intron phasing .
We have localized the binding epitopes of two murine monoclonal antibodies ( b7c9 and p5-2-1 ) that were shown previously to inhibit the activation of human coagulation factor xii by negatively charged surfaces .
Assessment of the platelet activity and plasma levels of c1-inh , activated factor xii ( xiia ) , and prothrombin fragment f1.2 ( f12 ) before and after infusion of 15 u/kg of c1-inh concentrate .
The kaolin-induced activation of factor xii ( xii ) to xiia was studied in plasminogen-free human citrated plasma treated with acetone in the presence of benzamidine 7.5 mm .
No activation occurred if factor xii was omitted .
A marked increase in factor xii was observed in addition to the expected rise of factor viii coagulant activity ( viii : c ) , factor viii related antigen ( viiir : ag ) and plasminogen activator , ddavp also produced a concomitant but less pronounced rise of factor vii , but there was no change in factors v , ix , x and xi .
Prothrombin activation fragment ( f12 ) is an index of in_vivo thrombin generation .
Experiments using purified enzyme of the k-k cascade indicated that neurotropin inhibited surface-mediated activation of coagulation factor xii ( fxii ) and the activation of prekallikrein by fxiia .
This indicates that the factor xii tenri present in disulfide-linked complexes with other proteins ( and itself ) is not converted to active forms , suggesting that attached proteins obstruct or delay the activation of factor xii via an inhibition of its binding to a negatively charged surface in_vitro .
The first enzyme , factor xii , of the intrinsic coagulation pathway is activated on the collagen fibers exposed in the damaged vascular wall , although the significance of this reaction in respect of the clotting process is ambiguous .
The effect of divalent metal ions on the rate of dextran sulfate dependent autocatalytic activation of human blood coagulation factor xii was studied at ph 7.4 and 25 degrees c. zn2+ and cu2+ , but not co2+ , increased the rate of factor xii activation induced by dextran sulfate with optimum effects at approximately 5 and 1 microm , respectively , while ca2+ acceleration required much higher concentrations ( millimolar ) .
In the activation of the contact system , blood coagulation factor xii and plasma kallikrein play central roles , and a specific inhibitor of these serine proteinases inhibited the release of bradykinin by s. aureus in human plasma .
As two examples , the novel procedure is used to analyse the autocatalytic activation of bovine trypsinogen and human blood coagulation factor xii ( hageman factor ) .
The ability of human hageman factor ( coagulation factor xii ) to bind to a glass surface and its susceptibility to limited proteolytic cleavage during the contact activation of plasma have been studied using normal human plasma and plasmas genetically deficient in factor xi , prekallikrein , or high molecular weight kininogen ( hmwk ) .
Specific types of activated factor xii increase following thrombolytic therapy with tenecteplase .
Possible basis for the apparent surface selectivity of the contact activation of human blood coagulation factor xii .
The incubation of rat or human plasma with degranulated mast cell ( dmc ) suspension did not cause the activation of plasma prekallikrein , but did cause a loss in the activity of coagulation factor xii , as ascertained by the lack of activation of prekallikrein in either the dmc-treated plasma by glass powder or in the incubation of dmc-treated human plasma with factor xii deficient plasma activated by kaolin .
Loss of the activity of human coagulation factor xii by a chymotrypsin-like protease activated in rat mast cells during degranulation with compound 48/80 .
Role of surface in surface-dependent activation of hageman factor ( blood coagulation factor xii ) .
However , the ability of the solid-phase assay to detect and quantitate alpha 2m-proteinase complexes when they are present was confirmed in control experiments with plasma samples to which performed alpha 2m-trypsin complexes had been added , or in which alpha 2m-kallikrein complexes had been generated by activation of hageman factor ( coagulation factor xii ) .
Activated platelets convert pre-bound factor xii to its active form , which then initiates the intrinsic coagulation cascade .
The nucleotide sequence of the cdna revealed that hgf activator is derived from the cooh-terminal half region of a precursor protein of 655 amino acids and that the precursor consists of multiple putative domains homologous to those observed in blood coagulation factor xii .
On endothelial cells , factor xii activation is secondary to prekallikrein activation and amplifies it .
Cold promoted activation and factor xii , prekallikrein and c1-inhibitor .
We evaluated activation of factor xii by measuring plasma levels of fxiia with a commercial elisa and cleavage of high molecular weight kininogen by performing sds page and immunoblotting analysis during 5 attacks in 5 different patients with hae and during 7 attacks in 3 patients with aae .
For the activation of factor xii by plasma kallikrein ( reaction 1 ) , high-mr kininogen was required when a low concentration of factor xii and kaolin was used .
Although sulfatide ( galactosylceramide i3-sulfate ) has been reported to activate blood coagulation factor xii ( hageman factor ) , it has been administered to animals without subsequent thrombus formation .
In complex , zymogen factor xii activates prekallikrein ( or factor xi ) by limited proteolysis to initiate the coagulation cascade .
Prothrombin fragment f1.2 ( f12 ) and beta-thromboglobulin ( beta-tg ) were determined as indicators of coagulation and platelet activation , respectively .
Evaluation of the biological activity of the heparinized surfaces was made by measuring the capacity for binding antithrombin ( at ) and inhibition of the activated coagulation factor xii ( fxiia ) .
The nucleotide sequence of hgf activator cdna shows that hgf activator is derived from the cooh-terminal region of a precursor of 655 amino acids by proteolytic cleavage of the bonds between arg372 and val373 and between arg407 and ile408 and that the precursor consists of multiple domains homologous to those observed in blood coagulation factor xii .
There was no significant difference in dd , fibrinogen , pt , ptt , at , proc-global , plasminogen , pai , alpha 2-antiplasmin , coagulation factor xii , basal and activated fibrinolytic capacity observed after the treatment .
Using a mab to factor xii ( c6b7 ) , we blocked the activation of the contact system in an established experimental baboon model in which escherichia coli was infused to produce lethal bacteremia with hypotension .
Since pge2 and prostacyclin can affect the activity of immunocompetent cells and bone resorbing osteoclasts , our finding indicates that thrombin and bradykinin , both of which are formed in inflammatory processes as a consequence of activation of the hageman factor ( coagulation factor xii ) , may have important roles in the modulation of the inflammatory response and the loss of alveolar bone in periodontitis .
Additionally , activated partial thromboplastin time ( aptt ) of the patient was disproportionately prolonged and there were reduced levels of coagulation factor xii in the patients and members of the maternal trait which are compatible with heterozygous factor xii deficiency .
The contact system proteins factor xii ( fxii ) , prekallikrein ( pk ) and high molecular weight kininogen ( hk ) have roles in coagulation , fibrinolysis , thrombin-induced platelet activation , cell adhesion and angeogenisis .
This hmg-i probably inhibits factor xii functions because its high positive charge favors competitive binding to an activating substance .
Contact activation of blood factor xii ( fxii , hageman factor ) is moderated by the protein composition of the fluid phase in which fxii is dissolved .
The binding of human factor xii and prekallikrein to vesicles of various compositions and the relationship to activation of factor xii were studied .
Acceleration of surface-dependent autocatalytic activation of blood coagulation factor xii by divalent metal ions .
The effect of zinc ions on kinetic and equilibrium steps that may contribute to the activation and subsequent autoactivation of human blood coagulation factor xii in the presence of 500-kda dextran sulfate was studied .
The domain organization of factor xii is analogous to those of several fibrinolytic proteins , including tissue plasminogen activator and urokinase , suggesting that factor xii belongs to the same protease subfamily as these two proteins .
Activation of the contact system of coagulation by a monoclonal antibody directed against a neodeterminant in the heavy chain region of human coagulation factor xii ( hageman factor ) .
These events clearly precede the death of the animal and appear to be initiated by an activation of coagulation factor xii ( hageman ) .
We conclude that enhanced factor xii susceptibility for kallikrein activation and factor xii autoactivation are distinct phenomena , the latter being necessary to support activation of the contact system in plasma .
Prothrombin fragment 1.2 ( f12 ) is an activation peptide generated during a critical event of blood coagulation , the conversion of prothrombin to thrombin .
Elevated fibrinogen , activated factor xii ( fxiia ) , and factor vii coagulant activity ( fviic ) are associated with higher risk of fatal ischemic heart disease .
(2) the incubation of factor xii alone in a quartz cuvette or in the presence of kaolin and hmw kininogen did not result in the activation of factor xii .
The in_vivo effect of pge1 on the fibrinolytic and hemostatic process was tested on 15 patients before and after treatment with alprostadil for 21 days using d-dimers ( dd ) , fibrinogen , prothrombin time ( pt ) , partial thromboplastin time ( ptt ) , antithrombin ( at ) , proc-global , plasminogen , plasminogen activator inhibitor activity ( pai ) , alpha 2-antiplasmin , coagulation factor xii , basal and activated fibrinolytic capacity ( fib cap ) .
Activated protein c ( apc ) -ratio , factor v ( fv ) g1691a and prothrombin g20210a mutation , protein c , protein s , antithrombin , coagulation factor xii , lipoprotein (a) and homocysteine .
The sulfatide-mediated activation of factor xii and prekallikrein in the presence of high-molecular-weight ( hmw ) kininogen was remarkably accelerated by 10 ( -5 ) m zinc ions .
Plasma levels of activated factor xii ( xiia ) , the initial product of contact activation , have therefore been measured by elisa in 2464 men aged 51 to 62 years , clinically free of chd , who were taking part in a prospective cardiovascular survey based in general medical practices .
We examined the platelet reaction to the alumina films and the intrinsic coagulation factor xii activation by the alumina films .
Washed platelets reconstituted in plasma obtained from two patients with coagulation factor xii deficiency were activated by oxidized cellulose with a prolonged lag phase .
Structural organization and chromosomal localization of the human hepatocyte growth factor activator gene--phylogenetic and functional relationship with blood coagulation factor xii , urokinase , and tissue-type plasminogen activator .
The results show that the contact activation of coagulation and complement systems are connected on si and ti , but not on al , via coagulation factor xii .
Molecular cloning and sequence analysis of the cdna for a human serine protease reponsible for activation of hepatocyte growth factor .structural similarity of the protease precursor to blood coagulation factor xii .
The plasma activity of factor xii , prekallikrein and high molecular weight ( hmw ) kininogen were measured in 24 patients with biopsy-proven iga nephritis and in 123 normal controls , using an activated partial thromboplastin time assay with the appropriate factor-deficient plasma as substrate .
The coding sequence of factor xii consists of multiple putative domains that are homologous to putative domains found in fibronectin and tissue-type plasminogen activator .
The hyaluronan-binding protease ( habp ) is a serine protease in human plasma which is structurally related to plasminogen activators , coagulation factor xii and hepathocyte growth factor activator .
These pulmonary lesions were prevented when the infected animals were treated with h-d-pro-phe-arg-chloromethylketone , an inhibitor of coagulation factor xii and plasma kallikrein , suggesting that inhibition of contact system activation could be used therapeutically in severe infectious disease .
Our data suggest that sulfatides stimulate factor xii activation via two distinct mechanisms :
In the present study , the assembly and function of activated factor xii ( fxiia ) , prourokinase ( pro-u-pa ) , high molecular weight kininogen ( h-kininogen ) , and prekallikrein on human umbilical vein endothelial cells ( huvec ) was investigated.
The assay was used to assess activation of factor xii in patients with renal failure , pregnancy and diabetes compared to a control group .
Approximately 110,000 corresponding to activated factor xii ( xiia ) , and mol .
It may be important for the mechanism of ( 1----3 ) -beta-d-glucan induced enhancement of plasma clotting to activate factor xii , to bind with fibrinogen , and to increase the local concentration of the clotting system by steric exclusion .
The resulting prorenin preparation could be activated at ph 7.5 by highly purified human plasma kallikrein , which was prepared from prekallikrein by activation with active factor xii fragment beta-factor xii a. activation proceeded at 4 and 37 c at a kallikrein concentration of 2 micrograms/ml , which is approximately 5% of the prekallikrein concentration in normal plasma .
The genes considered are ; alpha-fibrinogen , beta-fibrinogen , gamma-fibrinogen , prothrombin , tissue factor , factor v , protein s , complement component 4 binding protein , factor xi , factor xii , factor xiiia , factor xiiib , histidine rich glycoprotein , high molecular weight kininogen , kallikrein , von willebrands factor , platelet factor 4 , thrombospondin , antithrombin iii , alpha-1-antitrypsin , thrombomodulin , plasminogen , tissue plasminogen activator , urokinase plasminogen activator , plasminogen activator inhibitor-1 , plasminogen activator inhibitor-2 , protein c inhibitor , alpha-2-plasmin inhibitor , kallistatin , lipoprotein a , interleukin 6 , interleukin 1 , cystathionine-beta-synthase , and methylenetetrahydrofolate reductase .
Patients undergoing thrombolysis had a significant early increase in activated factor xii ( from 22 ng/ml at baseline to 47 ng/ml after 90 minutes ; p = 00001 ) , cleaved kininogen ( from 26% to 37% ; p = 0001 ) , and fragment 1 + 2 ( from 14 to 21 nmol/l ; p = 00001 ) , whereas the 24-hour levels were similar to baseline levels .
It was confirmed that activation of the kallikrein-kinin enzyme system in cryoglobulinemia might be initiated by activation of factor xii to factor xiia by cryoglobulin .
The amino acid and dna sequences in human factor xii showed considerable homology with the corresponding domains in other serine proteases , including prothrombin , plasminogen , tissue plasminogen activator , and urokinase .
Rutin and rutin coupled to bovine serum albumin , but not bovine serum albumin alone , were also demonstrated to activate factor xii .
In this paper we report the effect of sulfatides on the rate constants of factor xii activation by kallikrein and its isolated light chain ( the domain of kallikrein that contains the active site of the enzyme ) .
As was earlier demonstrated , secretion of medical leech exhibits high antithrombin activity of hirudin and inhibits contact activation of factor xii .
It was demostrated that the "quenched" non-equilibrium state reduces the rate of activation of the intrinsic systems , factor xii pathway , when compared to the fully annealed state .
Whether escherichia coli and staphylococcus aureus cell wall fractions can trigger the activation of prekallikrein was investigated in a mixture of purified human factor xii , prekallikrein , and high-relative-molecular-weight ( mr ) kininogen .
Hageman factor ( hf , factor xii ) is activated by glass , collagen , and ellagic acid , and initiates blood coagulation via the intrinsic pathway .
Since these proteins were rapidly liberated from platelets by the action of the stimulants , the present results demonstrate a negative role of platelets in the surface-mediated activation of factor xii and prekallikrein .
Inhibition of the activation of hageman factor ( factor xii ) by soluble human placental collagens types iii , iv , and v .
Comparison of the structure of factor xii with other proteins revealed extensive sequence identity with regions of tissue-type plasminogen activator ( the epidermal growth factor-like region and the kringle region ) and fibronectin ( type i and type ii homologies ) .
Physiological activation appears to occur along the surface of endothelial cells both by the aforementioned contact-initiated reactions as well as bypass pathways that are independent of factor xii .
The fibrinolytic system is activated by the conversion of plasminogen to plasmin by mediators such as tissue extract , plasma factor xii , or the exogenous activators urokinase ( uk ) and streptokinase ( sk ) .
A mab that neutralizes activated factor xii had no effect on tafi activation indicating that an intact contact system is not necessary for the activation of tafi .
We sought to determine whether the proteins of the contact system of plasma proteolysis ( factor xii , prekallikrein , high molecular weight kininogen , and c1 inhibitor ) were also activated after acute lung injury .
Platelets treated with collagen or thrombin were shown to both coagulant assays and cleavage studies to participate with hmw kininogen and kallikrein in the proteolytic activation of factor xi by mechanisms that are partially dependent upon and partially independent of factor xii .
Blood drawn from the aorta and coronary sinus immediately postoperatively was analyzed for activation of coagulation ( prothrombin fragment 12 and activated factor xii ) , myocardial injury ( myoglobin ) , and inflammation ( interleukin 8 ) by using an enzyme-linked immunosorbent assay .
Using both these methods , it is possible to distinguish between fletcher trait ( ppk deficiency ) and other contact factors such as factor xii and hmwk deficiencies , which do not activate with kaolin or dextran sulphate .
In the present study , the influence of plasma derived apas and beta 2 gpi on factor xii activation on the surface of very low density lipoprotein ( vldl ) was investigated .
Both rat plasmin and "plasmin" destroyed the capacity of high molecular weight kininogen ( hmwk ) to function as a cofactor in the activation of factor xii in rat plasma , without causing a corresponding release of the kinin part of the molecule .
The former also had activation of the intrinsic coagulation pathway as evidenced by decreased plasma prekallikrein ( p less than 0001 ) , kallikrein inhibitors ( p less than 0001 ) , and factor xii ( p less than 002 ) .
The amino acid sequence of the heavy chain of human alpha-factor xiia ( activated hageman factor ) was determined by automated edman degradation using the peptides produced by chemical and enzymatic cleavages of intact factor xii and alpha-factor xiia .
The results reported here indicate that activated species of hageman factor ( hf , factor xii ) , a protein that mediates blood clotting , fibrinolysis , and activation of the complement cascade , induce elaboration of interleukin 1 ( il-1 ) by human monocytes .
Contact activation was determined by a novel assay for the measurement of factor xii activity ( fxiia ) , and leukocyte response was measured by the release of granulocyte elastase .
Initiation of contact system activation in plasma is dependent on factor xii autoactivation and not on enhanced susceptibility of factor xii for kallikrein cleavage .
The thrombolytic regimen with half-dose reteplase in combination with abciximab caused in_vivo a lower systemic plasminemia and a lower paradoxical activation of the contact phase of the coagulation system ( measured as activated factor xii ) ; a lower paradoxical thrombin activation/generation ; and a lesser extent of fibrinogen breakdown compared with the reteplase regimen .
Stearic acid causes hypercoagulability of the blood by activation of factor xii and by aggregation of blood platelets .
Activation of prothrombin , as catalyzed by the prothrombinase complex ( factor x(a) , enzyme ; factor v(a) and phosphatidylserine ( ps ) -containing membranes , cofactors ) , involves production and subsequent proteolysis of two possible intermediates , meizothrombin ( mzii(a) ) and prethrombin 2 plus fragment 1.2 ( pre2 & f12 ) .
Epidemiological and genetic associations of activated factor xii concentration with factor vii activity , fibrinopeptide a concentration , and risk of coronary heart disease in men .
In this study the contribution of activation of the contact system to activation of the fibrinolytic system in_vivo was investigated in healthy volunteers and in factor xii deficient patients .
In this paper we report the effect of sulfatides on rate constants of factor xii activation by kallikrein and its isolated light chain .
The inhibitory activities of these five cationic proteins on the activation of factor xii and prekallikrein mediated with amylose sulfate , sulfatide and kaolin were different from each other .
Probing single-stranded dna and its biomolecular interactions through direct catalytic activation of factor xii , a protease of the blood coagulation cascade .
All measures of xii concentration related positively to viic after cold activation , the strongest being the measure of amidolytic activity following activation of factor xii ( xiiam ) ( r = 05 , p < 001 ) .
In a previous study we have shown that monoclonal antibody f1 ( moab f1 ) , directed against an epitope on the heavy chain of factor xii distinct from the binding site for anionic surfaces , is able to activate factor xii in plasma ( nuijens jh , et al :
The lipolysis of triglyceride-rich lipoproteins may provide a surface that supports the activation of factor xii ( fxii ) with subsequent activation of factor vii ( fvii ) .
For most of the collagen forms , the addition of factor xii inhibitor ( polybrene ) to blood brought about a remarkable delay of the initiation of coagulation , suggesting that the activation of factor xii on the collagen surface is one of main factors governing procoagulant activity .
Therefore , we studied the activation of factor xii ( fxii ) , prekallikrein , and fxi and the generation of thrombin in 52 hypertriglyceridemic patients before and after 12 weeks of triglyceride-lowering treatment with gemfibrozil or n-3 polyunsaturated fatty acids .
The data obtained emphasize the role of factor xii activation by adrenaline for physiological regulation of blood coagulability .
Ampholine leads to an increase of activity of factor viii and in_vitro at the same time inhibits the activation of factor xii .
The plasma kinin-forming cascade can be activated by contact with negatively charged macromolecules leading to binding and autoactivation of factor xii , activation of prekallikrein to kallikrein by factor xiia , and cleavage of high molecular weight kininogen ( hk ) by kallikrein to release the vasoactive peptide bradykinin .
By means of contact of the vessel contents with the collagen , there is an additional activation of the coagulation system by factor xii possible .
In normal plasma , the serine protease inhibitor alpha 1-antitrypsin ( alpha 1-at ) plays little or no role in the control of plasma kallikrein or activated factor xii fragment ( factor xiif ) , this function being performed by cl-inhibitor .
The mechanism of activation of contact system could be the result of an anionic interaction of residues within the region 1-11 of betaa1-42 with factor xii , and of kallikrein generation .
These observations are consistent with conversion of prekallikrein to kallikrein by factor xii , and with evidence that kallikrein proteolysis in_vitro is activated in the cold by alteration of its binding to c-i esterase inhibitor .
We studied three patients with angioedema for evidence of activation of the contact system and found that during a symptomatic period they had decreased levels of prekallikrein , a substrate for the activated forms of factor xii , and reductions in high-molecular-weight kininogen , a substrate for plasma kallikrein .
Treatment of plasma from dr with acetone ( 25% v/v ) induced a conversion of hmwk into a state which was non-functional as a cofactor in the surface-dependent activation of factor xii , and the passage of plasma from dr through a lysine-sepharose column altered the hmwk present to a substance that released kinin only very slowly by incubation with hpk .
After denaturation of c1-inh at ph 4-5 , factor xii becomes capable of activating prekallikrein .
It is concluded that in the presence of contact surface the activation of factor xii and the sequential activation of factor xi and of factor ix results in the activation of factor vii .
In contrast , kallikrein activation of factor xii correlated with the amount of sulfatide-bound factor xii and was relatively insensitive to the density of factor xii on the vesicle surface .
It also inhibited , but to a lesser extent , activated factor x. the inhibition constants ( ki ) of sac i toward activated factor xii and plasma kallikrein were 5.3 x 10 ( -8 ) and 7.2 x 10 ( -9 ) m , respectively .
The addition of purified human factor xii to this plasma restored the increase in viic and the activation of factor xii .
The main conclusions are that zn2+ is required to initiate contact activation , modulating factor xii for autoactivation .
Cholesterol sulfate was found to display a strong ability to trigger the activation of factor xii and prekallikrein in the presence of hmw kininogen .
The effect of zinc ions on the surface-mediated activation of factor xii and prekallikrein was studied , using the contact system reconstituted with the purified proteins from bovine and human plasmas .
Functional correlation between kallikrein and factor xii activated in human plasma .
Using a purified preparation of hageman factor , we examined the ability of schistosome extracts and secretory products to inhibit the activation of human hageman factor ( factor xii ) in an amidolytic assay .
We measured fibrinogen , d-dimers ( ddi ) , alpha(2) -antiplasmin activity , tissue plasminogen activator antigen ( t-pa ag ) , plasminogen , plasminogen activator inhibitor antigen ( pai-1 ag ) , and factor xii ( fxii ) of the coagulation .
It is well known that activated factor xii ( fxiia ) and kallikrein are rapidly inactivated in plasma as a result of reaction with endogenous inhibitors .
The autocatalytic activation of bovine factor xii by factor xiia was not demonstrated .
The role of augmented hageman factor ( factor xii ) titers in the cold-promoted activation of factor vii and spontaneous shortening of the prothrombin time in women using oral contraceptives .
As with heparin , sg from g. crinale does not activate factor xii , while the polysaccharide from b. occidentalis activates factor xii in high concentrations , which could account for its procoagulant effect at high doses on rats .
Thrombin-antithrombin iii complexes ( tat ) , antithrombin iii ( atiii ) , prothrombin fragment f 1 + 2 ( f 1 + 2 ) , kallikrein-like activity ( kk ) , activated factor xii ( fxiia ) , plasmin alpha 2-antiplasmin complexes ( pap ) , fibrinogen , d-dimers ( dd ) , tissue-type plasminogen activator ( t-pa ) .
An analysis of the activators of single-chain urokinase-type plasminogen activator ( scu-pa ) in the dextran sulphate euglobulin fraction of normal plasma and of plasmas deficient in factor xii and prekallikrein .
1. the endogenous and exogenous activating system of blood clotting and possible reasons for lower bleedings with factor xii deficiency. 2. role of the hageman factor in activating fibrinolysis. 3. influence on the liberation of kinin. 4. correlations towards the complement system. 5. possible inhibitory effect of platelet aggregation .
Abnormalities in the contact activation through factor xii in fujiwara trait : a deficiency in both high and low molecular weight kininogens with low level of prekallikrein .
These results suggest that high-mr kininogen accelerates the surface-mediated activation of factor xii and prekallikrein by enhancing the susceptibility of factor xii to plasma kallikrein , on the one hand , and the affinity of factor xiia for prekallikrein , on the other hand .
At baseline , the median ( 25th , 75th ) prothrombin activation fragment 1.2 ( f12 ) level was 2.56 ( 205 , 320 ) nmol/l , and the median d-dimer level was 0.26 ( 019 , 038 ) mug feu/l .
To assess whether ds500 interferes with the sulphatide and the acidic phospholipid in activating factor xii , plasma deficient in prekallikrein was incubated with phosphatidylinositol phosphate ( ptdinsp ) and sulphatide at the conditions necessary for activation with these surfaces and various concentrations of ds500 .
Suspensions of peripheral blood mononuclear cells ( pbmc ) , monocytes , t or b lymphocytes , platelets or granulocytes , and cell-depleted supernatant fluids of these suspensions inhibited activation of hageman factor ( hf , factor xii ) by ellagic acid , a property not shared by erythrocytes .
The inositol-phospholipid-accelerated activation of prekallikrein by activated factor xii at physiological ionic strength requires zinc ions and high-mr kininogen .
Here we describe the structure of the fibronectin type 1 module which appears twelve times in fibronectin and is also found in factor xii and tissue plasminogen activator .
As the molecular weight decreased , the ability to activate factor xii and to promote inhibition of coagulation proteases in the presence of antithrombin and heparin cofactor ii diminished .
Risk of coronary heart disease and activation of factor xii in middle-aged men .
The supernatant fluid ( conditioned medium ) of cultured human vascular endothelial cells inhibits activation of hageman factor ( factor xii ) , whether by ellagic acid , bovine brain sulfatides , or bismuth subgallate ; inhibition appears to be a property of one or more proteins in the culture supernates .
In view of the risk of thromboembolic complications in nonpregnant individuals with factor xii deficiency , pregnant women with a prolonged activated partial thromboplastin time and no lupus anticoagulant or anticardiolipin antibody syndrome should also be investigated for deficiencies of factors viii , ix , and xii .
No significant difference was found comparing prothrombin fragment 1.2 ( f12 ) levels 1 week before surgery and on the morning of surgery ( 049 ng/ml versus 067 ng/ml , p = ns ) , suggesting that no activation of blood coagulation had taken place following the reduction of anticoagulant therapy .
Increased euglobulin fibrinolytic potential in women on oral contraceptives low in oestrogen--levels of extrinsic and intrinsic plasminogen activators , prekallikrein , factor xii , and c1-inactivator .
Kinetics of activation and autoactivation of human factor xii .
The data indicate that the plasma of a lepidosaur contains a kininogen but , unlike the plasma of chelonians and crocodilians , does not contain a prekallikrein activator related to factor xii .
Preincubation of celite with chfi or cytochrome-c prevented the activation of factor xii and the subsequent activation of factor vii and the pt .
This paper reviews data reported in the literature and results of our experiments on the transcriptional control of factor xii by estrogens and on the activation of factor xii in the plasma .
The writhing reaction in mice induced by kaolin , a factor xii activator , was studied .
Therefore , the current concept that activation of factor xii plays a pivotal role in initiating the sequence of events linking postprandial lipemia to activation of factor vii is contradicted by the present study .
Endotoxin showed prekallikrein activation via factor xii .
A highly purified protein from lysates of human umbilical vein endothelial cells ( huvecs ) inhibited the activation of factor xii [hageman factor ( hf ) ] and removed factor xiia from an activating surface , thus impairing hf-dependent coagulation and kinin-releasing activities .
Judging from these findings , the c-terminal domain may more effectively inhibit the association of factor xii and hk with the cell surface by binding to cell-binding regions , and hence would predominantly contribute to the inhibition of activation of the kallikrein-kinin system .
Activated protein c resistance ratio , activated partial thromboplastin time , and factor xii showed the strongest heritabilities , with 71.3% , 83.0% , and 67.3% , respectively , of the residual phenotypic variation attributable to genetic effects .
The circumstances in which activation is initiated by factor xii autoactivation or by these factor xii bypasses are yet to be defined .
Evidence was provided that serotonin did not lower the plasma level of factor xii of the coagulation system , but the level of a factor of significance for the activation of factor xii .
To investigate the relationship between coronary artery disease , activated factor xii and other circulating factors , we studied levels of fxiia , cholesterol , triglycerides , fasting insulin , fibrinogen , fvii : c , t-pa antigen and pai-1 antigen .
Factor xi complexed with antibody did not bind to high molecular weight kininogen or undergo activation and cleavage by two-chain factor xii .
Activation was assessed upon admittance to the intensive care unit and 48 h thereafter , based on the measurement of factor xii - ( fxii ) , prekallikrein - and factor xi ( fxi ) antigen levels , as well as on the detection of fxia-fxia inhibitor , fxiia-c1-inhibitor , and kallikrein-c1-inhibitor complexes , respectively .
Pka did not correct the coagulant defect in factor xii deficient plasma , was purified from huvec cultured in factor xii-deficient serum , was not detected by antibody to factor xii , did not activate fxi , and was not inhibited by a neutralizing antibody to fxii .
Women taking ocs had normal factor xii levels , moderately elevated prekallikrein levels , and decreased kallikrein inhibitor levels , a pattern not consistent with activation of the intrinsic pathway .
Almost all available glycosaminoglycans ( heparin , heparan sulfate , bovine and tuna dermatan sulfate , chondroitin 4 - and 6-sulfates ) reduced ( 12 to 30 times ) the catalytic efficiency of kallikrein ( in a nanomolar range ) on the hydrolysis of plasminogen ( 03 to 18 microm ) and increased ( 19 to 77 times ) the enzyme efficiency in factor xii ( 01 to 10 microm ) activation .
Previous studies have suggested that human platelets can promote the activation of factor xi by two different mechanisms , one requiring factor xii and adp-treated platelets and the other requiring collagen-treated platelets in the apparent absence of factor xii .
At several time points before and after pci , the activation of both the platelet and the coagulation system was determined by measuring beta-thromboglobulin ( beta-tg ) and prothrombin fragment f1.2 ( f12 ) , respectively , in venous blood and in blood emerging from a microvascular injury ( shed blood ) .
Lipolysis of triglyceride-rich lipoproteins activates coagulant factor xii : a study in familial lipoprotein-lipase deficiency .
The phagocytes that had not been activated previously proliferated for about ten generations in f12 medium supplemented with 10% fetal calf serum depending on a growth factor produced by hamster brain , liver or lung cells .
Previous studies have shown an increased risk of coronary heart disease with increased levels of activated factor xii ( fxiia ) .
Inhibition of thrombin-induced platelet aggregation was demonstrated with factor xiia but not with factor xii zymogen or factor xiif , indicating that the conformational exposure of the heavy chain following proteolytic activation is required for inhibition .
This inhibitory property blocks the adsorption of hageman factor ( factor xii ) to glass , thereby preventing the activation of hageman factor , but does not impair the coagulant or amidolytic activity of already activated hageman factor ( factor xiia ) .
The assay is capable of detecting activated factor xii in human plasma and can be used to assess early detection of the intrinsic blood coagulation pathway .
We prospectively measured the plasma levels of activated factor xii , cleaved kininogen , prothrombin fragment 1 + 2 ( as indexes of the contact phase and coagulation activation ) , and interleukin-6 and c-reactive protein ( crp ) ( as indexes of inflammation ) in 39 patients hospitalized for ami within 12 hours of symptom onset : .
Activation of the contact system occurred after ddavp infusion in healthy volunteers and was absent in factor xii deficient patients .
Polyacrylamide gel electrophoresis studies using 125i-factor xii as a marker show that the appearance of amidolytic activity correlates with factor xii cleavage , that activation goes to completion and that virtually all factor xiia formed is present as the two-chain , 80,000 mr form , alpha-factor xiia .
We determined serially in the patients up to 10 days after admission factor xii and the beta-factor xiia inhibition , kallikrein-like activity , prekallikrein , c1-esterase inhibitor , kallikrein inhibition , high molecular weight kininogen as indicators of the contact phase and bradykinin generation , thrombin-antithrombin iii ( tat ) complex as marker of the activated coagulation cascade , fibrinogen , plasminogen , plasminogen activator inhibitor-1 ( pai-1 ) , tissue-type plasminogen activator ( tpa ) , and d-dimers as indicators of the fibrinolytic system .
Based on these properties ( ie binding of factor xii without inducing autoactivation ) , ds15 and ds5 were predicted to be inhibitors of contact system activation induced in plasma by ds500 , which indeed was observed .
The contact system comprises three zymogens ( factor xii , factor xi , and prekallikrein ) and the non-enzymatic activation cofactor , high-molecular-weight kininogen ( hk ) .
Plasminogen activators in dextran sulfate-activated euglobulin fractions : a molecular analysis of factor xii - and prekallikrein-dependent fibrinolysis .
In the post-occlusion samples , there was a significantly increased concentration of beta-thromboglobulin and factor xii , as well as a shortening of the activated partial thromboplastin time , indicating that an activation of the coagulation system takes place during the period of venous occlusion .
Activation of hageman factor ( factor xii ) by sulfatides and other agents in the absence of plasma proteases .
Anticoagulant activity test using activated partial thromboplastin time ( aptt ) is more sensitive in assessing heparin-immobilized surfaces , since it corresponds to factor x and initiates the inhibition of factor xii and thrombin .
It is well known that a negatively charged surface activates the contact system , consisting of factor xii , prekallikrein , and high-molecular-weight kininogen .
Also , trypsin could easily activate factor xii , but in contrast to kallikrein , this activation was independent of moab f1 .
The addition of edta ( 2 mm ) did not alter the extent of factor xii activation induced by contact surface , but it did inhibit the rise in viic .
The experiments described indicate that , paradoxically , eosinophils and certain of their constituents inhibit the activation of hageman factor ( hf , factor xii ) .
A system was developed for studying the activation of factor xii ( hageman factor ) in the presence of dextran sulfate ( ds ) .
Our results demonstrate the significant influence of factor xii on blood platelets activation by oxidized cellulose .
Activation of the intrinsic coagulation cascade was suggested by low levels of factor xii , prekallikrein , and kallikrein inhibitors in 12 of 17 patients .
In this study , the contact system , in which the activation of factor xii and plasma kallikrein is included , is highlighted .
Mechanism of surface-mediated activation of bovine factor xii and prekallikrein .
Detailed investigations for the intrinsic and extrinsic pathways of coagulation , fibrinolytic system , kinin-kallikrein system , and complement system were performed because factor xii is known as an activator of these systems .
Conventional chd risk factors , the activation peptides of factor ix and factor x , factor vii activity and antigen , activated factor xii , prothrombin fragment 1+2 , fibrinopeptide a , and fibrinogen were measured in 1153 men aged 50 to 61 years who were free of myocardial infarction at recruitment .
The predominant autolytic form of human kallikrein , beta-kallikrein , was used to localize the high molecular weight kininogen ( hk ) binding site on kallikrein as well as the substrate recognition site for activated factor xii on prekallikrein.
Contact system activation , in_vitro , is triggered by activation of factor xii ( fxii ) on binding to an activator , such as negatively charged surfaces .
Blood pressure ( bp ) , plasma prekallikrein ( pk ) , and the extent of activation of factor xii ( xii-act ) were studied after the intravenous injection into rats of dextran ( macrodex ) , the ionic radiographic contrast substance iodipamide ( biligrafin ) , or the non-ionic contrast substance iohexol ( omnipaque ) .
Induction of acute cholecystitis by activation of factor xii .
The contact phase of intrinsic clotting involves factor xi , factor xii , fletcher factor , and a fourth activity that we call contact activation cofactor ( cac ) .
Since the effects of ph and ionic strength on the rate constants of kallikrein-dependent factor xii activation in the presence of sulfatides correlated with effects on the binding of kallikrein , it is concluded that under these conditions surface-bound factor xii is activated by surface-bound kallikrein .
Mab f1-induced contact activation required the presence of factor xii , prekallikrein , and high molecular weight kininogen and , in contrast to activation by negatively charged surfaces , was not inhibited by the presence of polybrene .
The kinetic analysis of the accelerating effect of zinc ions demonstrated that zinc ions reduce the km values and increase the vmax values on the activation of factor xii by kallikrein and on the activation of prekallikrein by factor xiia .
In sera from patients with hereditary angio-oedema who lack the alpha(2) -glycoglobulin c1 inhibitor , silicates and other potent activators of clotting factor xii induced far less c1 esterase activity than did the weaker factor xii activators , carrageenin and cellulose sulphate .
The value of vmax/km increased 26.4-fold in the former reaction and 2.8-fold in the latter reaction , indicating that zinc ions accelerate mainly the activation of factor xii by kallikrein .
During contact activation in normal human plasma a rapid cleavage of high mw kininogen along with kinin liberation occurs in a reaction that is dependent upon the presence of prekallikrein and factor xii ( hageman factor ) .
In the presence of hmw-kininogen the rate of activation of factor xii and consequently that of prekallikrein was markedly enhanced .
Association between prothrombin activation fragment ( f12 ) , cerebral ischemia ( s-100beta ) and international normalized ratio ( inr ) in patients with ventricular assisted devices .
Inhibition of the activation of hageman factor ( factor xii ) by peripheral blood cells .
However , at lower concentration of prekallikrein the rate of activation of prekallikrein by factor xii was shown to be a sigmoidal curve and slower than that by factor xiia .
Blood was anticoagulated alone or in combination with citrate , ethylenediaminetetraacetatic acid , corn trypsin inhibitor ( cti , an inhibitor of activated factor xii ) , heparin , enoxaparin , recombinant tick anticoagulant peptide ( rtap ) , or recombinant hirudin .
All proteinases tested activated either clotting factor xii or prothrombin in_vitro , thus resulting in generation of thrombin .
Consistent with the finding that a major part of the asp-induced vl was reduced by a potent kallikrein inhibitor , soybean trypsin inhibitor that does not affect asp enzymatic activity , asp activated prekallikrein but not factor xii to generate kallikrein in a dose - and incubation time-dependent manner .
As much thrombin was formed during cardiopulmonary bypass ( measured by the prothrombin activation fragment f1 + 2 and thrombin-antithrombin complexes ) as in normal patients , showing that factor xii was not necessary for thrombin generation .
As the zn2+-independent activating surface ( sulfatide ) induced quenching in the fluorescence intensity , while the zn2+-dependent activating surface ( ptdinsp ) did not , the quenching , whether it was caused by sulfatide or zinc ions , was assigned to a change in the conformation which resulted in a molecular structure of factor xii that could be autoactivated .
We demonstrate here that during a 2 hour incubation time plasma deficient in either factor xii or high molecular weight kininogen ( hk ) fails to activate , as compared to normal plasma , but with more prolonged incubation , factor xii-deficient plasma gradually activates while hk-deficient plasma does not .
Using patient blood samples and isolated proteins , we identified a novel class of factor xii activators .
During cardiopulmonary bypass , thrombin is generated , which is thought to be initiated by activation of factor xii on the surface of the bypass equipment .
This report describes a plasma prekallikrein assay which , unlike methods that employ contact activation , is not affected by the factor xii or hmw kininogen content of the plasma analyzed .
It is suggested that heparin does not prevent the activation of factor xii ( hageman factor ) by glass or the subsequent formation of active factor xi ( plasma thromboplastin antecedent ) .
Levels of functional alpha 2m correlated significantly with levels of factor xii and prekallikrein suggesting that decreases in alpha 2m at least in part were due to contact activation .
In all instances a profound shortening of the recalcification time was found , but only in patients with a dual response could an increased activation rate of factor xii be detected .
Activation of the system was not even detected by the sensitive substrate ac-phe-arg-nan ( acetyl-phenylalanyl-arginyl-4nitro-anilide ) , indicating that the plasma of these species does not possess either factor xii and/or prekallikrein .
When blood ( plasma ) contacts certain foreign surfaces , factor xii can activate and trigger a series of reactions leading to cleavage of kininogens with subsequent release of bradykinin .
Enzymatic activities of activated and zymogen forms of human hageman factor ( factor xii ) .
Plasma kallikrein activated spontaneously during the purification of prekallikrein (i) and acetone-activated plasma kallikrein ( ii ) were at ph 7.4 both capable of reducing the capacity of purified human high molecular weight kininogen ( hmrk ) to function as cofactor in the contact phase activation of factor xii in a crude plasma preparation .
The "mobility shift" assay in native gels has been used to visualize the kinetics of activation of factor xii by dextran sulfate as well as the formation of kallikrein-cleaved high molecular weight kininogen .
To study the interaction of antithrombin-heparin cofactor and heparin with activated factor xii , we have employed two forms of this enzyme with widely differing physical characteristics and biologic potencies .
Competitive-protein adsorption in contact activation of blood factor xii .
The scu-pa activator activity ( scupa-aa ) in the def of plasmas deficient in factor xii or prekallikrein was about half of that in the def of normal plasma .
In this overview , we present recent developments on the structure/function relationships of the contact activation proteins : factor xii , high molecular weight kininogen , prekallikrein , and factor xi , with the emphasis on the localization of domains on these proteins that are involved in the interaction with activators , substrates and cofactors .
A monoclonal antibody recognizing an iscosapeptide sequence in the heavy chain of human factor xii inhibits surface-catalyzed activation .
Both kinds of kallikrein reduced the capacity of human high molecular weight kininogen to function as a cofactor in the surface-mediated activation of factor xii in a crude plasma preparation .
Thus the results indicate that the factor xii and prekallikrein-mediated activation of single chain u-pa ( scu-pa ) operates as a major pathway of scu-pa activation in whole plasma in contact with dextran sulfate .
In view of such data it is concluded that the present results obtained with ac in rats are probably due to an inhibition of plasma kallikrein and its activation of factor xii .
Inhibition of the activation of hageman factor ( factor xii ) by beta 2-glycoprotein i .
It further indicates that the in_vitro demonstration of factor xii as an activator for other biochemical pathways might be of minor importance in_vivo , as alternative pathways for activation of these systems exist .
Complement system activation was assessed from plasma levels of c4a , c3a , cleavage products of complement factor b , soluble terminal complement complex , c1 inhibitor and c4-binding protein , and the contact phase of coagulation was assessed from plasma levels of activated factor xii and cleaved high-molecular-weight kininogen .
An increase in d-dimer and t-pa-antigen was registered in all patients , while factor xii and plasminogen were decreased , indicating an activated fibrinolysis .
Direct potential-mediated and time-controlled activation of purified human factor xii ( fxii ) immobilized on carbon has been demonstrated .
Most reports in the literature state that human plasma kallikrein does not destroy the capacity of human high molecular weight kininogen ( hmrk ) to function as a cofactor in the contact phase activation of factor xii .
Most surface modifications were more activating of factor xii , both in plasma and on the material surfaces , than the control polyurethanes .
Isolation of bovine platelet cationic proteins which inhibit the surface-mediated activation of factor xii and prekallikrein .
In the presence of corn inhibitor , the activation of prekallikrein was observed , but in the presence of trasylol , the activation of factor xii was not observed .
Plasma of birds and snakes probably lacks a prekallikrein activator analogous to mammalian factor xii but treatment with exogenous proteases ( pig pancreatic kallikrein and/or trypsin ) generates [thr6 , leu8] -bk ( chicken ) , [ala1 , thr6] -bk ( python ) and [val1 , thr6] -bk ( colubrid snakes ) .
Corn trypsin inhibitor , a specific inhibitor of factor xiia , inhibited this thrombin-antithrombin complex generation in blood in contact with pvc , which is not considered an efficient activator of factor xii .
In the present study using truncated abeta peptides , we identified the region between residues 1 and 11 as critical for the activation of the contact system in_vitro through an ionic interaction of abeta with factor xii and/or kallikrein .
It is the receptor for prekallikrein which when bound to hk becomes activated to kallikrein by an endothelial cell enzyme system independent of activated forms of plasma factor xii .
Earlier reports have suggested possible activation and consumption of factor xii during hemodialysis .
These studies demonstrate the importance of factor xii in the cold activation of factor vii and shortening of the pt and indicate that inhibitors to activated factor xii or xii fragments are useful in inhibiting in_vitro shortening of the pt .
In addition , xiia , a measure of activity due to enzymes derived from factor xii , related strongly to many of the measured lipoprotein variables , particularly vldl cholesterol and triglycerides , supporting the hypothesis that negatively charged molecules such as free fatty acids on larger lipoprotein particles provide the contact surface necessary to activate factor xii .
It was found that human blood plasma after the contact with norepinephrine loses its ability to increase the baee-esterase activity , when tanic acid , which activates factor xii ( hageman factor ) , was added .
Placement of ventricular assist devices ( vads ) has been associated with consumption of circulating contact proteins and persistent generation of activated contact proteins such as factor xii and high molecular weight kininogen .
We found that the concentration of plasmin alpha2antiplasmin complex markedly increased for at least 10 hours after the fatty meal , but that the activation of factor xii and the concentration of prothrombin activation fragment1+2 decreased after the fatty meal .
In this model , activation of the plasma kallikrein/kinin system on endothelial cells is not initiated by factor xii autoactivation , as seen on artificial surfaces .
Plasma levels of fibrinopeptide a ( fpa ) , fibrin d-dimer , thrombin antithrombin ( tat ) complex , prothrombin fragment 1.2 ( f12 ) , urokinase-type plasminogen activator ( upa ) , tissue-type plasminogen activator ( t-pa ) and plasminogen activator-inhibitor 1 ( pai-1 ) were measured before and after therapy , as was the cellular expression of the genes for tissue factor ( tf ) and interleukin-1 beta ( il-1 beta ) .
Comparison of the kinetics obtained at different levels of zinc , which included amounts lower than the residual concentration introduced by nacl in the incubation mixture , suggested that the addition of zn2+ up to 5 microm lowered the mean number of sites available for the binding of factor xii to the surface from 220 to 172 and increased the rate of the first-order activation of factor xii by one order of magnitude , from ( 16 +/- 04 ) x 10 ( -4 ) s ( -1 ) to ( 80 +/- 04 ) x 10 ( -4 ) s ( -1 ) in the presence of 550 nm dextran sulfate .
Activation of coagulation was assessed by assaying the levels of activated factor vii ( viia ) , activated factor xii ( xiia ) , prothrombin fragments 1 and 2 ( f1 + 2 ) , thrombin-antithrombin iii ( tat iii ) complex and fibrinogen .
Significant positive associations with bmi were seen for factor viic , activated factor xii , antithrombin activity , protein c activity and plasminogen activator inhibitor-1 activity .
Inositolphospholipid-accelerated activation of prekallikrein by activated factor xii and its inhibition by beta 2-glycoprotein i .
Further investigation of the effect of zn2+ on factor xii activation demonstrated a complete dependence on the presence of dextran sulfate , lack of inhibition by soybean trypsin inhibitor , the appearance of alpha-xiia as the primary reaction product , and reaction kinetics characteristic of an autocatalytic process .
These data and the retarded activation of platelets in plasma with factor xii deficiency indicate that due to negatively charged oxidized cellulose probably activation of the contact coagulation system occurs and this leads to the activation of platelets and fibrin formation .
The purified igg did not directly inhibit the amidolytic activity of kallikrein , but it did inhibit the activation of pk to kallikrein by activated factor xii .
In some patients , activation of factor xii presumably also contributed to plasminogen activation in sf , since levels of factor xiia-c1 inhibitor in sf were increased in 8 of the 42 patients and correlated , as did u-pa-pai levels , with levels of pap complexes .
Hypertensive offsprings had significantly higher plasma levels of plasminogen activator inhibitor-1 antigen , fibrinogen , fibrin degradation products , protein s antigen and factor xii activity , while no differences were observed to the other haemostatic variables studied .
By contrast , except for insignificant changes in protein c activity and activated factor vii content , specific markers of plasma hypercoagulability , that is , thrombin-antithrombin ( tat ) complexes , prothrombin activating factor f 1+2 , activated factor xii ( xiia ) , and dimer d were all markedly increased .
In 1991 it was demonstrated that , besides factor xii , thrombin is capable of activating factor xi in_vitro .
Of five iggi/k murine monoclonal anti-human prekallikrein antibodies produced ( mabs ) , mab 13g11 was selected for studying interaction of prekallikrein with factor xii and high-mol-wt kininogen ( hmwk ) during activation on a surface .
The function of the heavy and light chain of human plasma kallikrein in the activation of factor xii .
Only limited data exist on changes in activated factor xii ( xiia ) levels following mechanical revascularisation , such as percutaneous coronary intervention ( pci ) .
This complex represents a 1 : 1 stoichiometric combination of activated factor xii and inhibitor .
This finding suggests that haemaphysalin interferes with the association of factor xii and the prekallikrein-hk complex with a biologic activating surface by binding to these cell-binding domains , leading to inhibition of the reciprocal activation between factor xii and prekallikrein .
Cold-promoted activation of prorenin was less than or equal to 1% in plasma deficient in factor xii or prekallikrein .
The activation system used here was as follows ; (1) activation of prekallikrein by factor xii , (2) activation of factor xii by plasma kallikrein and (3) activation of prekallikrein by factor xiia .
Recent experimental evidence supports a vascular insult through the activation of factor xii pathways as the initial event .
A monoclonal antibody that inhibits activation of human hageman factor ( factor xii ) .
The autoactivation kinetics of purified factor xii ( fxii ) in the presence of dextran sulfate of 500000 da was reexamined assuming the existence of two preceding activation steps .
Recent data suggest that activation of the kinin-forming cascade can occur on the surface of endothelial cells , even in the absence of factor xii .
Cat data of 40 patients with chd ( age range from newborn to 18 years ) were compared to data using standard coagulation parameters such as prothrombin ( fii ) , antithrombin ( at ) , tissue factor pathway inhibitor ( tfpi ) , prothrombin fragment 1.2 ( f 12 ) , thrombin-antithrombin ( tat ) , activated partial thromboplastin time ( aptt ) , and prothrombin time ( pt ) .
Plasma levels of antithrombin iii ( at-iii ) , protein c ( pc ) , plasminogen ( pg ) and alpha 2-antiplasmin ( ap ) , total and free protein s ( ps ) , thrombin-antithrombin iii complex ( tat ) , f1.2 fragment of prothrombin ( f12 ) , fibrinogen ( fg ) , soluble fibrin monomers ( fm ) , tissue-plasminogen activator ( t-pa ) , plasminogen activator inhibitor 1 ( pai-1 ) , total fibrinogen/fibrin degradation products ( tdp ) and d dimer ( dd ) were determined prior to the therapeutic regime , at the end of the treatment , and 24 hours later .
Contact activation is initiated when the plasma proteins , hageman factor ( factor xii ) , prekallikrein and high molecular weight kininogen interact with negatively charged materials .
Activation of factor vii during alimentary lipemia occurs in healthy adults and patients with congenital factor xii or factor xi deficiency , but not in patients with factor ix deficiency .
Contact activation can be initiated by interaction of factor xii , prekallikrein ( pk ) and high molecular weight kininogen ( hk ) with inorganic negatively charged biologic macromolecules , or upon cell surfaces , or interaction with membrane protein derivatives such as aggregated beta amyloid .
Plasma proteins are instantaneously adsorbed onto nonendothelial surfaces ; plasma factor xii is cleaved into two serine proteases ; and platelets are activated to aggregate , adhere to adsorbed fibrinogen , and release granule contents .
Other contact phase proteins such as factor xi , factor xii , and prekallikrein bound to curliated e. coli , but not to an isogenic curli-deficient mutant strain , suggesting that contact phase activation may occur at the surface of curliated bacteria .
Recent studies from our laboratories have confirmed that atiii inactivates factor xiia and factor xiif , but only contributes 2% to 3% to the inhibition of activated factor xii species in plasma .
Experiments with purified kallikrein. c-1-inh and partly purified beta-factor xiia , and activation experiments in plasmas deficient in either factor xii or prekallikrein , demonstrated the specificity of both rias .
Rat high mr kininogen also accelerated approximately 10-fold the surface-dependent activation of rat factor xii and prekallikrein , which was mediated with kaolin , amylose sulfate , and sulfatide .
Other sulfate ester derivatives of testosterone , estrone , pregnenolone and dehydroepiandrosterone and cholesterol tested did not show any effect on the activation of factor xii and prekallikrein .
Immunoassays for prothrombin fragment 1.2 ( f12 ) provide a specific measure of thrombin generation and offer potential value in detecting activation of the coagulation system and monitoring anticoagulant therapy .
We assessed the long-term effects of n-3 pufas on postinfarct variations of tissue factor ( tf ) , activated factor xii ( fxiia ) and fibrin monomer ( fm ) , and expected additional statin treatment to modify thrombogenicity .
Recent investigations have shown that there is a physiologic pathway for assembly and activation of this system independent of factor xii .
Acute physiology and chronic health evaluation ( apache ) ii score , multiple organ failure ( mof ) score , plasma levels of thrombin-antithrombin iii complexes ( tat ) , antithrombin iii ( at iii ) , protein c antigen , factor xii , and plasminogen activator inhibitor type 1 antigen ( pai-1 ) , neopterin , and interleukin 6 ( il-6 ) .
The plasma levels of plasminogen activator inhibitor-1 antigen , thrombomodulin , tissue factor pathway inhibitor antigen , fibrinogen , and factor xii were determined before and after 6 months of therapy .
This increase was coincident with both the cleavage of factor xii and the complex formation of activated factor xii with its plasma inhibitors , which were determined by immunoblotting procedure .
In this article we have reviewed the current knowledge regarding the involvement of factor xii in contact activation .
The zn ( ii ) concentration dependence of the acceleration of factor xii activation reactions were sigmoid and characterized by hill coefficients of 3.3-4.3 , suggesting that cooperative binding of at least four zinc ions to factor xii was responsible for the zn ( ii ) potentiating effect .
Reconstitution of these plasmas with highly purified factor xii or prekallikrein restored normal prorenin activation .
Reduction of contact activation related fibrinolytic activity in factor xii deficient patients .further evidence for the role of the contact system in fibrinolysis in_vivo .
Platelet ( beta-thromboglobulin ) release , complement ( c3a ) activation , the activation of free plasma and surface-bound factor xii were studied using fresh , human blood ( no anticoagulant ) or citrated plasma in control and surface-modified polyurethane .
Chf patients had higher levels of bradykinin ( p = 0008 ) , activated factor xii ( p = 0049 ) , interleukin-6 ( p = 0050 ) and tumour necrosis factor receptor ii ( stnfrii ) ( p = 0026 ) than controls .
The formation of factor xiia is further promoted by the fact that surface-bound factor xii is likely more susceptible to proteolytic cleavage and by the fact that the activated factor xiia is capable of auto-activating its own zymogen factor xii .
The inhibitors were able to interfere with the kinin release by human plasma kallikrein at concentrations as low as 1-10 ( -10 ) m. however , despite this remarkable antikallikrein effect and the known importance of plasma kallikrein in the activation of hageman factor ( factor xii ) , the compounds had only little influence on the early stages of blood coagulation .
The capacity of tgp-l and tgp-csc to activate factor xii was shown to depend on the presence of rutin , a substance chemically similar to quercetin and ellagic acid , which are known activators of factor xii .
Recent data suggest that activation of the kinin-forming cascade can occur on the surface of endothelial cells , even in the absence of factor xii .
Partial identification of the zn2+-binding sites in factor xii and its activation derivatives .
We assessed the relation between admission levels of activated factor xii type a ( xiiaa ) , and long-term all-cause and cardiac mortality and recurrent troponin t ( tnt ) positive cardiovascular events in a consecutive cohort of 870 patients admitted with a clinically strongly suspected acute coronary syndrome ( acs ) .
The system is largely impervious to the level of activated factor xii , given that a trace ( non-zero ) level is present .
Its activation requires the availability of phospholipid and of activated factor xii ( factor xiia ) , or factor xia .
In_vitro studies in purified plasma systems have suggested that triglyceride-rich lipoproteins such as chylomicrons , very low density lipoproteins , and their remnants promote activation of factor vii through activated factor xii ( xiia ) and the intrinsic coagulation pathway .
In a prospective study , prothrombin fragment 1 and 2 ( f12 ) , thrombin-antithrombin complex ( tat ) , antithrombin , d-dimer , plasmin-alpha(2) -antiplasmin complex ( pap ) and plasminogen activator inhibitor-1 ( pai-1 ) were measured in 20 patients with crohn's disease ( cd ) , 18 with ulcerative colitis ( uc ) , and 19 with giant cell arteritis during active and inactive disease , as well as in 51 controls without inflammation .
In order to enhance the activation of factor xii on a surface the hmw-kininogen molecule had to be intact .
Activation of human hageman factor ( factor xii ) in the presence of zinc and phosphate ions .
The initial step in the formation of thrombin via the intrinsic pathway is the activation of hageman factor ( factor xii ) .
To investigate these hypotheses , isolated platelets were tested for their capacity to promote the activation and cleavage of purified factors xii and xi in various mixtures of purified factor xii , kallikrein , high molecular weight kininogen , and factor xi .
The threshold between the two system states - complete factor xii activation , or complete stability - is dependent on the kinetic balance between the catalytic rate of autoactivation and rate of enzyme ( factor xiia ) inhibition .
Effect of surface-immobilized heparin on the activation of adsorbed factor xii .
To determine the role of zn ( ii ) -factor xii interactions in the rate-enhancing effect of zn ( ii ) on factor xii activation demonstrated in the preceding paper , equilibrium binding of zinc ions to factor xii , and the spectroscopic changes accompanying this binding were investigated .
In this system , the suppression remained significant in the presence of an excess of exogenous activated factor xii .
Platelet numbers and plasma concentrations of p-selectin , prothrombin fragment 1.2 ( f12 ) , soluble fibrin , d-dimers , and von willebrand factor ( as a marker of endothelial cell activation ) were measured and corrected for hemodilution .
This review focuses on articles , which report phenotypization of animals deficient in the contact system proteins factor xii , factor xi and high-molecular-weight kininogen , as well as novel links between factor xii and edema formation , discovery of new in-vivo activators of factor xii , and functions of the factor xii downstream protease factor xi .
C3a ( desarg ) increased throughout storage in both types of pc , but without a commensurate increase in the terminal complex sc5b-9 or activation of factor xii .
With both systems , no increases in activated factor xii or in prothrombin fragment f 1 + 2 have been observed .
The influence of the product of blood coagulation contact phase of factor xii and of its activated form on the reduction reaction of nitrobule terazolium by human neutrophils was investigated .
These results indicate that the activation of bovine factor xii is initiated by the attack of factor xii on prekallikrein , followed by the reciprocal activation of factor xii by plasma kallikrein generated .
These studies demonstrate that platelets can promote the proteolytic activation of factor xii by kallikrein and of factor xi by both factor xii-dependent and factor xii-independent mechanisms .
With more prolonged incubation , factor xii deficient plasma gradually activates and hk deficient plasma does not .
Recent studies have pointed to the serine protease thrombin and autoactivation by activated factor xi as possible alternatives to factor xii as activators of factor xi .
The relations of plasma activated factor xii ( fxiia ) concentration and a common polymorphism ( c46t ) of the factor xii gene with hemostatic status and risk of coronary heart disease ( chd ) were examined by prospective surveillance .
The plasma levels of activated factor xii ( fxiia ) , the peptides released upon activation of factor x ( fxpep ) and factor ix ( fixpep ) , activated factor vii ( fviia ) , prothrombin fragment 1 + 2 ( f1 + 2 ) and fibrinopeptide a ( fpa ) served as indices of activity along the coagulation pathway .
Activation of hageman factor ( factor xii ) by bismuth subgallate , a hemostatic agent .
Incubation of protoporphyrin with purified factor xii resulted in activation as measured by amidolysis of a chromogenic substrate .
Simultaneously with the shortening of the elt an activation of factor xii and of kallikrein was observed .
Rigorous analysis of kinetic data establishes that , between 0.02 and greater than 90% of the reaction , the activation of factor xii is described by a mechanism of autoactivation of factor xii by factor xiia .
The role of bovine high-molecular-weight ( hmw ) kininogen in contact-mediated activation of bovine factor xii :interaction of hmw kininogen with kaolin and plasma prekallikrein .
Bell and alton phospholipids and gum acacia ( used as a vehicle in one of the preparations ) activated factor xii as did platelets , but folch phospholipid did not .
Effect of heparin on the inactivation rate of human activated factor xii by antithrombin iii .
Here , we studied in detail the mechanism underlying the activation of factor xii by moab f1 using purified proteins .
Rhapc alone dose-dependently prolonged the activated partial-thromboplastin time ( aptt ) but not the prothrombin time ( pt ) , and dose-dependently suppressed two indices of thrombin generation , namely prothrombin fragment f 1.2 ( f 12 ) generation and thrombin-antithrombin ( tat ) complex formation .
In contrast , dextran sulphate of mr 15,000 ( ds15 ) and 5000 ( ds5 ) neither induced contact system activation in plasma , nor supported autoactivation of factor xii , although both of these ds species enhanced the rate of activation of factor xii by kallikrein in the purified system .
Only the negatively charged amphiboles ( crocidolite and amosite ) are able to activate factor xii ( hageman factor ) .
In those >55 years it was significantly higher in females than males and associated positively with age , fibrinogen and , in males , activated factor xii ( fxiia ) .
Inhibition of the activation of hageman factor ( factor xii ) by aprotinin ( trasylol )
Similarly in factor xi-deficient plasma , the stearate-induced increase in viic and the factor xii activation were 48% and 69% of that found in normal plasma .
These data confirm that the n-terminal part of the heavy-chain region of factor xii contains a binding site for negatively charged activating surfaces , and indicate that other sequences , possibly located on the second epidermal-growth-factor-like domain and/or the kringle domain , contribute to the binding of factor xii to these surfaces .
However , this 'minimal' factor-xii protein displays a marked protease activity and , although lacking five regulatory domains of factor xii , is bound and activated by negative charges and promotes coagulation with high efficiency .
On admission , the patient's activated partial thromboplastin time ( aptt ) was prolonged ( 271 s ) , and activated clotting time was 500 s. his factor xii level was <3%. the sonoclot signature showed an abnormal pattern .
It is well known that on artificial surfaces , binding and autoactivation of factor xii ( fxii ) is the initiating event of plasma prekallikrein ( pk ) activation .
Human plasma prekallikrein .studies of its activation by activated factor xii and of its inactivation by diisopropyl phosphofluoridate .
At 330 microm sulfatides and ph 7.0 the rate constants of factor xii activation were 5.3 x 10(6) m-1 s-1 and 4.2 x 10(4) m-1 s-1 for kallikrein and its light chain , respectively .
The platelet membrane , activated by adp collagen or thrombin , can promote the proteolytic activation of factor xii to factor xiia in the presence of kallikrein and high molecular weight kininogen .
Influence of operative trauma on factor xii and inhibitor of plasminogen activator .
This finding demonstrated the strong influence of the interaction of other plasma constituents on the membrane surface and as such the binding and subsequent activation of factor xii may be altered possibly due to competitive binding and steric hindrance .
This potentiator further increased the activation of factor xii , also in a dose-dependent fashion .
Aptt , factor vii , factor viii , factor xii , fibrinogen , prothrombin , total antithrombin , normalised activated protein c sensitivity ratio ( n-apc-sr ) , protein c , protein s and free protein s. results : .
Contact activation factors in plasma from pregnant women--increased level of an association between factor xii and kallikrein .
Bismuth subgallate ( bsg ) is a heavy metal compound which is effective in lowering the incidence of hemorrhage after adenotonsillectomy and has been demonstrated to activate factor xii .
Control of human coagulation by recombinant serine proteases .blood clotting is activated by recombinant factor xii deleted of five regulatory domains .
So , once other causes of rpl were excluded , the patient was diagnosed an unusual form of aps associated to antibodies to factor xii , reduced factor xii plasma levels , transient la and prolonged activated partial thromboplastin time .
The platelets adhesion , thrombus formation and factor xii activation are effectively suppressed with respect to the segmented polyurethane when vp-dmam copolymers with high vp contents are incorporated into bs as t-ipns .
It was found that as little as 2.3 x 10 ( -9 ) microm of factor xiia ( 1/10000 of its plasma concentration ) is enough to cause the complete activation of factor xii and prekallikrein ( pk ) during the first 20 s of the preincubation phase .
Thus , the appearance of factor-xii-dependent coagulant activity correlates with the limited proteolysis of factor xii when normal or prekallikrein-deficient plasma is activated by sulfatides or kaolin .
In contrast , significant changes in coagulation activation markers ( prothrombin fragments f12 , thrombin-antithrombin iii complex , and fibrin monomers ) were found only in group 3. conclusions : .
At 330 microm sulfatides , ph 7.0 and 100 mm nacl the rate constants of factor xii activation were 5.34 x 10(6) m-1 s-1 and 4.17 x 10(4) m-1 s-1 for kallikrein and its light chain , respectively .
At least part of this activation is potentiated by the contact activation phase of plasma coagulation , in particular activated factor xii .
It may also explain hypotension , by release of bradykinin from high molecular weight kininogen , and complement activation , by activated factor xii , that has been demonstrated in these patients .
The absence of abnormal bleeding in congenital deficiency of factor xii , the protease that activates factor xi in the intrinsic cascade , has stimulated a search for other mechanisms for factor xi activation .
The contribution of activation of the contact system to activation of the fibrinolytic system in_vivo was investigated in healthy volunteers and in factor xii deficient patients .
It was found that haemaphysalin inhibited activation of the plasma kallikrein-kinin system by interfering with reciprocal activation between factor xii and prekallikrein .
During blood-material interaction , the enzymes factor xii fragment ( factor xiif ) and kallikrein are generated ( contact activation ) .
The temperature dependence of the reaction showed unusual behavior that may be related to the conformational change of factor xii following binding ; the rate of factor xii activation had a relatively low temperature optimum ( 0-47 degrees c ) that was sensitive to choice of surface and salt concentration .
Our results reveal k-k system activation in ards patients , with a significant fall in factor xii ( p less than 005 ) , prekallikrein ( p less than 001 ) , alpha-2-macroglobulin ( p less than 001 ) and high molecular - weight kininogens ( p less than 0005 ) , with a rise in c1-esterase inhibitor ( p less than 0001 ) in comparison with patients with cpo .
Compensatory changes in plasma levels of factor xii procoagulant activity , activated protein c and of alpha 2-antiplasmin were not observed .
Contact of plasma with a negatively charged surface activates prekallikrein and factor xii reciprocally .
We also demonstrate that normal plasma is capable of activating upon interaction with the cells whereas plasma deficient in factor xii , prekallikrein and hk do not activate .
(5) the inhibitor has no effect on the activation of factor xii by celite .
Among a variety of artificially-sulfated polysaccharides and native polysaccharide sulfates , amylose sulfate ( mw= 380,000 and sulfur content , 191% ) and sulfatide were found to have the most efficient ability to trigger the activation of prekallikrein by factor xii .
During the early events of coagulation of human blood by the intrinsic pathway , factor xii is activated to a form which can activate factor xi , and is proteolytically fragmented to smaller species ( 30,000 daltons and 70,000 daltons ) which have lost most of the ability to activate factor xi but which can activate prekallikrein rapidly .
Nm does not alter markers of complement activation ( c1-c1-inhibitor complex and c5b-9 ) , or indicators of thrombin formation ( f12 ) .
An algal sulfated galactan has an unusual dual effect on venous thrombosis due to activation of factor xii and inhibition of the coagulation proteases .
The contact activation of the intrinsic pathway of coagulation consisting of factor xii , prekallikrein and high mr kininogen has been implicated to play a role in the intrinsic fibrinolysis .
The histopathological findings are also reported ; these are most likely attributed to the shwarzman reaction or the activation of the factor xii pathways .
This finding supports the concept that autoactivation is an enzymic process , initiated by traces of activated factor xii which are invariably present in factor xii preparations .
Microfilarial extracts ( 01 mg/ml ) completely inhibited activation of hageman factor ( factor xii , at 005 u/ml ) as measured in an amidolytic assay .
Among the other etiologies not associated with a bleeding tendency , there were 31 proved or suspected cases with inhibitors of the ptt , most of whom were children , 2 factor xii deficiencies , 2 prekallikrein deficiencies and 4 contact phase activations .
Although the initiation of activation of plasma prekallikrein is independent of factor xii , kallikrein-mediated factor xiia generation , in turn , accelerates the activation of the system .
The effect of zinc ions ( zn ( ii ) ) on the activation of factor xii in the absence of a procoagulant surface was investigated by initial velocity kinetic studies at i = 0.15 , ph 7.4 , and 25 degrees c. zinc ions at concentrations greater than 160 microm potentiated 99-fold the kcat/km for the activation of factor xii by kallikrein and , at an optimum concentration of 110 microm , accelerated 140-fold the apparent kcat/km for factor xii autoactivation .
Preoperative blood coagulation scan revealed prolonged activated partial thrombin time of 105.6 s ( control , 303 s ) , and a decrease in factor xii level of 3% ( normal ; 70-120% ) .
From the data available today , it seems that such reactions are triggered by negatively charged biomaterials which are capable to activate factor xii , leading among others to the generation of bradykinin .
This is underscored by the fact that factor xii activation is rather slow in prekallikrein-deficient plasma .
Reconstituted collagen is not capable of activating factor xii but causes intrinsic coagulation by activating platelets .
However , c1-inh supplementation significantly reduced decreases in plasma levels of factor xii and prekallikrein and abrogated the systemic appearance of c4b/c , indicating substantial inhibition of activation of the contact system and the classical complement pathway , respectively .
The molar ratio of the protein cofactor to factor xii for optimal activation was found to be approximately 1 : 1. the apparent km value and the kcat/km value for plasma kallikrein on factor xii were calculated to be 4 nm and 5.2 x 10(7) s-1 x m-1 , respectively .
Together , these results indicate that cooperative interactions of zn ( ii ) with factor xii induce structural changes in the zymogen that facilitate its proteolytic cleavage and activation .
In all patients serial blood samples were analysed for plasma recalcification time and factor xii activation rate .
Upon incubation with moab f1 alone , factor xii was auto-activated in a time-dependent fashion , activation being maximal after 30 hours .
Now we report that peripheral blood lymphocytes are capable of producing immunoglobulins in response to polyclonal activation during culture for 10 days in medium consisting of one part ham's f-12 and one part iscove's modified dulbecco's medium supplemented with sodium bicarbonate , bovine crystalline insulin , human transferrin , 2-mercaptoethanol , and bovine serum albumin .
Instead , collagen appeared to accelerate clotting by activating hageman factor ( factor xii ) on the basis of the following findings :
This critical controlling protein has a major inhibitory effect on c1 , kallikrein , activated factor xii of the intrinsic coagulation system , and on plasmin .
1. the role of clotting factor xii in the activation of the complement subunit c1s to c1 esterase was examined.2 .
Statistical analysis demonstrated pregnancy caused increased factor vii ( p = 00313 ) , factor x ( p = 00156 ) and factor xii ( p = 00156 ) activity , fibrinogen concentration ( p = 00156 ) , t-pa ( p = 00313 ) , plasminogen activator inhibitor-1 ( p = 00156 ) and fbdp levels ( p = 00313 ) .
Inhibition of the activation of hageman factor ( factor xii ) by eosinophils and eosinophilic constituents .
Bound at the surface , the zymogens factor xii and prekallikrein are thought to be involved in a so-called reciprocal activation mechanism in which factor xiia activates prekallikrein to kallikrein , which in turn converts factor xii to factor xiia .
The negative results of this study mitigate against the hypothesis that collagen activation of platelet-associated factor xi represents a physiologically significant mechanism for initiating clotting independent of factor xii .
Among a variety of foreign surfaces , amylose sulfate and sulfatide were the most efficient in the activation reaction of factor xii and prekallikrein .
In an earlier study , activated species of hageman factor ( factor xii ) induced elaboration of interleukin-1 by human monocytes .
These results indicated that the autoactivation and the kallikrein activation of factor xii were dependent on different properties of the surface component .
The activated carbon caused a moderate activation of factor xii and production of kallikrein , while there was no activation for the lines , double filter or resin .
However , variations in the concentration of c1inh and of factor xii could not explain the differences in viic and in xiia between late pregnancy and control plasmas following cold activation under the same conditions .
Plasma prekallikrein activity was low in the propositus , whereas normal levels of antigen could be found , suggesting a defect of kallikrein activation due to factor xii deficiency .
In previous studies , we have shown that administration of monoclonal antibody ( moab ) c6b7 against human factor xii to baboons challenged with a lethal dose of escherichia coli abrogates activation of the contact system and modulates secondary hypotension .
It is suggested that the reduced extent of activation of factor xii observed in plasma from rats injected intravenously with dextran , or rat plasma that has been passed through a column with lysine-sepharose , is due to the loss of functional hmwk caused by plasmin activated in_vivo or on the column .
We studied whether microbial proteinases from the opportunistic pathogens candida albicans , pseudomonas aeruginosa and serratia marcescens activate the blood clotting cascade by using normal human plasma , human plasmas deficient in clotting factor xii or x , and also by using purified clotting factors xii , x and prothrombin .
Inhibition of the activation of hageman factor ( factor xii ) by complement subcomponent c1q .
Whereas plasma of the snakes waglerophis merremii ( wm ) and crotalus durissus ( cd ) , were shown to contain factor xii , prekallikrein , kininogen , kininases and to present a low but definite activation rate of the kinin system , the plasmas of bj , bothrops mojeni ( bm ) and oxyrophus trigeminus ( ot ) , yielded only kininogen and kininases .
Taken together , these data (i) confirm that clotting factor xii functions as a mitogenic growth factor and ( ii ) demonstrate that factor xii activates a signal transduction pathway , which includes a mitogen-activated protein kinase .
The activation of factor vii under these conditions involves the generation of enzymes derived from factor xii ( xiia ) .
Activated factor vii , activated factor xii , fragment f ( 1+2 ) , and d-dimer plasma levels were measured in 37 patients with cu and 37 controls .
Recombinant alpha 1-antitrypsin pittsburgh ( met 358----arg ) is a potent inhibitor of plasma kallikrein and activated factor xii fragment .
The activation of purified fxi by activated bovine factor xii ( fxiia ) , a reaction independent of high molecular weight kininogen ( hk ) , was not inhibited by either antibody .
Binding and activation properties of human factor xii , prekallikrein , and derived peptides with acidic lipid vesicles .
The formation of apolipoprotein b-74 , a fragment of apolipoprotein b-100 , in blood plasma in_vitro is shown to occur only at temperatures below 15 degrees c , and is promoted by exposure to glass and other surfaces known to activate factor xii .
Cleaved high-m(r) kininogen , activated factor xii and plasmin-antiplasmin complexes were measured in ascitic fluid and plasma .
The extent of activation of factor xii was only insignificantly influenced by the 1 + 1 ( v/v ) dilution of the plasma preparation with a suspension of kaolin .
Factor vii can be activated by factor xiia , generated from factor xii upon activation of the contact system of coagulation .
Inhibition of the activation of hageman factor ( factor xii ) by extracts of schistosoma mansoni .
The intrinsic system is activated by the contact of factor xii with a negatively charged surface , most likely collagen .
The biologic activity of c1 esterase , activated forms of factor xii and kallikrein at sites of vascular inflammation may be regulated by c1 inhibitor ( c1 inh ) elaborated by endothelial cells .
Based on this probable identification , evidence is provided that the concentration of active factor xii determines the rate of activation of plasma kallikreinogen , and that the activation may be blocked by polybrene .
Apc-sr was inversely correlated ( p < 001 ) with factor viii and fibrinogen in patients and with prothrombin activation fragment 1.2 ( f12 ) in controls .
Another plasma arginine esterase with properties suggestive of permeability factor is activated by factor xii in the presence of synthetic substrates , but only at low ionic strength .
The zn ( ii ) enhancement of the rates of factor xii activation decreased both above and below ph 7.4 with midpoint ph values of 6.5-7.0 and 8.0 , consistent with histidine and possibly water ligands mediating zn ( ii ) binding to the protein .
Its activity is initiated when appropriate triggers of the contact system are added , and the activation depends on the presence of factor xii and prekallikrein in plasma .
Role of hmw kininogen in surface-mediated activation of factor xii .
These results suggest that triafestin-1 and triafestin-2 inhibit activation of the kallikrein-kinin system by interfering with the association of factor xii and high molecular weight kininogen with biological activating surfaces , resulting in the inhibition of bradykinin release in an animal host during insect blood-feeding .
This review is intended to be a critical state-of-the-art overview of the activation and inhibition of the proteins ( factor xii , prekallikrein , high molecular weight kininogen , and factor xi ) of the contact phase of coagulation .
Ellagic acid , a known activator of factor xii , produced similar alterations as obtained in anaphylactic shcok .
The increased rate of activation of factor xii in late pregnancy can contribute to the increased reactivity of factor vii .
High mr kininogen increases the activation rate of prekallikrein by activated factor xii on a surface .
(3) the rates of activation of prekallikrein by factor xii and by factor xiia were approximately the same at higher concentration of prekallikrein .
We suggest that impairment of fibrinolytic activation related to severe factor xii deficiency might have contributed to the delay of dissolution of the subdural hematoma which , under ordinary circumstances , would have formed chronic subdural hematoma .
We investigated a new elisa for measuring activated factor xii ( fxiia ) in plasma .
To examine whether bradykinin generated by the activation of the contact phase of blood coagulation is involved in the pathogenesis of edema occurring after acute exposure to high altitude , 15 mountaineers were examined at 490 m and 1 , 3 , and 5 days after arrival at 4,559 m. the clotting activity levels of factor xii , factor xi , plasma prekallikrein , and high-molecular-weight kininogen ( hmwk ) were measured , and plasma kallikrein-induced proteolytic cleavage of hmwk was assessed by ligand blotting by use of radiolabeled factor xi .
The activation of prekallikrein by factor xii fragments ( xiif ) , during incubation in plastic tubes was previously noted to be increased by high molecular weight ( hmw ) kininogen as well as other plasma proteins .
Heparin and high molecular weight peo produced the greatest activation of factor xii in the free plasma form , but low molecular weight peo and glucosamine produced the greatest activation of surface-bound factor xiia .
Activation of factor xi in plasma is dependent on factor xii .
A monoclonal antibody recognizing an icosapeptide sequence in the heavy chain of human factor xii inhibits surface-catalyzed activation .
The variable bleeding tendency associated with a genetic deficiency of factor xi ( fxi ) and the lack of bleeding disorders in individuals with a genetic deficiency of factor xii ( fxii ) suggest an alternative mechanism for fxi activation in_vivo .
The cold activation , due to deficiency of c1 esterase inhibitor , was not suppressed by polybren in_vitro ( factor xii activation inhibitor ) but was prevented by aprotinins ( kallikrein inhibitors ) .
An hmg-i protein from human endothelial cells apparently is secreted and impairs activation of hageman factor ( factor xii ) .
Treatment of aortic smcs with factor xii , as well as activated factor xii , resulted in a rapid and transient activation of a mitogen-activated/extracellular signal-regulated protein kinase with peak activity/tyrosine phosphorylation observed at 5 to 10 min of exposure .
A mechanism of writhing reaction induced by kaolin , a known activator of factor xii , was studied .
This material and other glycosaminoglycans ( gags ) were tested for their ability to accelerate the reciprocal activation of factor xii and prekallikrein and the autoactivation of factor xii .
Their ability to accelerate reciprocal activation of factor xii was investigated by spectrophotometry .
In this study we have examined the interaction of a group a streptococcus with structurally related proteins , including plasmin , glu-plasminogen , tissue plasminogen activator , kallikrein , factor xii , prothrombin , thrombin , trypsin , and urokinase .
It is suggested that the partial blockade of dextran-induced shock is correlated with an inhibition of activation of pk and factor xii .
The coagulation studies , the similarity of anaphylactic results with those produced by a single injection of ellagic acid , and the effective inhibition of the anaphylactic and the ellagic acid-induced activation of these pathways by lysozyme all suggest that factor xii itself becomes activated in rat anaphylaxis .
Beta2gpi exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase , tenase , and factor xii activation .
In many patients , however , a biochemically detectable hypercoagulable state ( as represented by elevated levels of the coagulation activation marker prothrombin thrombin fragment f12 ) was demonstrated .
Synergistic platelet integrin signaling and factor xii activation in poly-n-acetyl glucosamine fiber-mediated hemostasis .
Thrombin generation was measured in 60 patients with congenital heart disease using the calibrated automated thrombography and compared to data using standard coagulation parameters such as prothrombin , antithrombin , tissue factor pathway inhibitor , prothrombin fragment 1.2 ( f 12 ) , and activated partial thromboplastin time .
Bismuth subgallate , an agent that initiates clotting via activation of factor xii , has been advocated for use in controlling bleeding during tonsillectomy and adenoidectomy .
The dextran sulfate-dependent activation of u-pa required both factor xii and prekallikrein , but did not require either plasminogen or factor xi .
Influence of zn2+ on the kinetic events that contribute to the 500-kda dextran-sulfate-dependent activation of factor xii ( hageman factor ) .
Cleavage of hmw-kininogen by kallikrein decreased the enhancing effect of hmw-kininogen , there being an inverse relation between the bradykinin-generated and the capacity to enhance factor xii activation .
On endothelial cells , the activation of the plasma kallikrein/kinin system is not initiated by factor xii autoactivation as seen on artificial surfaces .
Plasminogen activator inhibitor-1 antigen , tissue plasminogen activator antigen , fibrinogen , fibrin degradation products , thrombomodulin , protein s antigen , protein c activity , von willebrand factor ag , factor vii and factor xii activity .
These results imply that zinc ions induce a conformational change in factor xii that makes it a better substrate for its enzyme activators .
A new chromogenic assay for factor xii in plasma was designed by the use of the soluble activator kalliplastin , the substrate h-d-hht-gly-arg-pna and a synthetic inhibitor of plasma kallikrein ( pefabloc pk ) .
The addition of small amounts of factor xii ( fxii ) to fxii-deficient plasma induced a large increase in contact activation-dependent pa activity , as measured in a dextran sulfate euglobulin fraction , which may be ascribed to fxii-dependent activation of plasminogen activators like prekallikrein .
We found no evidence of a relationship between activated factor xii and disease .
A glycoprotein of mol wt ca. 18,000 daltons isolated from cured tobacco leaves ( tgp-l ) and from cigarette smoke condensate ( tgp-csc ) activated factor xii in normal human plasma in_vitro as measured by (a) shortening of the partial thromboplastin time , (b) shortening of the lysis time of euglobulin clots , and (c) generation of kinin activity .
From these results , it was concluded that the activation of bovine plasma factor xiii by thrombin must be accompanied by a limited proteolysis of the arginyl-glycyl bond located in the n-terminal region of the a chain , liberating the "activation peptide." the possibility of activating factor xii with other porteinases was examined using factor xa [ec 34216] , factor xiia , kallikreins [ec 34218] , urokinase [ec 349926] , trypsin [ec 34214] , ficin [ec 34223] , papain [ec 34222] , and bromelain [ec 34224] .
Studies with purified hageman factor ( factor xii ) demonstrate that this inhibitory property is directed against the activation of hageman factor .
Under conditions where nm level of calmodulin was able to show full activation of myosin light chain kinase and cyclic-nucleotide phosphodiesterase , the fragments of calmodulin at concentrations as high as 20 microm failed to activate these enzymes in the presence of ca2+. the fragments tested were ala1-lys75 ( f12 ) , ala1-arg74 ( f12' ) , lys75-lys148 ( f34' ) , met76-lys148 ( f34' ) , asp78-lys148 ( f34 ) , ala1-arg106 ( f123 ) , and his107-lys148 ( f4 ) .
High affinity binding of factor xiia to an electronegative surface controls the rates of factor xii and prekallikrein activation in_vitro .
That adp - or collagen-treated platelets can promote the proteolytic activation of factor xii in mixtures containing kallikrein and hmw kininogen was shown by (1) the proteolytic cleavage of factor xii , (2) the development of factor xiia coagulant activity , and (3) the proteolytic cleavage of 125i-labeled factor xii .
The evolution in mammals of the zymogens of the contact activation system of coagulation ( factor xii , prekallikrein and factor xi ) has been investigated .
Sulfatide ( galactosylceramide i(3) -sulfate ) , one of the glycosphingolipids of the platelet cell membrane , is thought to be involved in blood coagulation systems via activation of factor xii .
Investigation of the proteins adsorption , platelet adhesion , thrombus formation and factor xii activation is presented .
Contact activation in human plasma is triggered by zinc ion modulation of factor xii ( hageman factor ) .
A possible role of bovine platelets in the surface-mediated activation of factor xii and prekallikrein was studied , using the contact system reconstituted with the purified proteins from bovine plasma .
During the second phase of cpb , after release of the aortic crossclamp , factor xii and thrombin were strongly activated in both groups indicated by a sharp increase in concentrations of t/at complex as well as fpa .
Accelerating effect of zinc ions on the surface-mediated activation of factor xii and prekallikrein .
Localization of distinct functional domains on prekallikrein for interaction with both high molecular weight kininogen and activated factor xii in a 28-kda fragment ( amino acids 141-371 ) .
Contact activation system proteins ( eg , factor xii , kallikrein ) have been implicated as direct or indirect activators of plasminogen .
Incubation of pt-xi with purified factor xii , hmwk , and kaolin produced activated platelet factor xi clotting activity and , concomitantly , the generation over time of a new chain on reduced sds-page of mr = 44,500 .
It appears that patients with polycythemia vera have chronic activation of the coagulation system , probably initiated by activation of factor xii .
We demonstrate herein that during a 2-h incubation time , plasma deficient in either factor xii or high molecular weight kininogen ( hk ) fail to activate kinin-forming cascade as compared to normal plasma .
For the autocatalytic activation reaction of factor xii in the presence of optimal zn ( ii ) , apparent km and kcat values of 2.4 microm and 0.041 min-1 , respectively , were determined , but these parameters were not resolvable in the absence of the metal ion .
The first event leading to the activation of the plasma kallikrein-kinin system is the surface-dependent conversion of factor xii to an active enzyme .
There was no evidence that the rapid initial kinin release in plasma from allergic patients caused by submaximum concentrations of hog pancreas kalikrein or by acetone-activated human plasma (2) was due to an increased level of prekallikrein activator ( activated factor xii ) , to prekallikrein itself or to a factor possibly positioned between active factor xii and prekallikrein .
Activation of human blood coagulation factor xi independent of factor xii .factor xi is activated by thrombin and factor xia in the presence of negatively charged surfaces .
In_vitro tests showed an increase of fibrinolysis by activation of the endogenous pathway via factor xii and prekallikrein .
Pk activation occurs on ecv304 cells or matrix prepared without serum or in human factor xii deficient serum , indicating that the pk activator is not factor xiia .
The activation is caused by kallikrein generated from prekallikrein by activated factor xii .
The medication did not affect fibrin plate lysis area or the plasma level of plasminogen activator , alpha-2-antiplasmin , alpha-2-macroglobulin , c1 inactivator or factor xii .
Overall , the results are consistent with a model in which factor xii undergoes conformational changes upon binding to the activating surface .
Two antibodies ( a101 and a104 ) recognised common conformational structures in r-apo(a) , prothrombin , factor xii , plasminogen and its tissue-type and urokinase-type activators .
To test this hypothesis , dogs were injected intravenously with ellagic acid or rutin , known polyphenol activators of factor xii , or with escherichia coli endotoxin , also known to activate factor xii , and monkeys were injected intravenously with ellagic acid .
Endothelial cells are in fact severely affected by endotoxin and may even be removed from the vascular wall , thus making accessible the subendothelial activator of factor xii .
When blood comes into contact with negatively charged surfaces , a small amount of factor xii is adsorbed and activated which , in turn , generates kallikrein from prekallikrein .
Our observations indicates that the plasma contact system is activated in ascites from patients with gastrointestinal cancer : factor xii is activated , plasma kallikrein is present in complex with the protease inhibitor alpha 2-macroglobulin , and the plasma kallikrein substrate high molecular weight kininogen , is highly degraded .
Prolongation of activated partial thromboplastin time was associated with reduced factor xii and prekallikrein , whereas levels of factors viii , ix , xi , and high molecular weight kininogen were elevated .
The activation of plasminogen by hageman factor ( factor xii ) and hageman factor fragments .
Thus , this study shows that binding of ligands to the kringle domain , which does not contribute to the proposed binding site for negatively charged surfaces , may induce activation of factor xii .
As mab f1 can also induce this conformational change , this antibody may provide a unique tool in studies of the activation of factor xii .
Since the concentration of zinc ions required to induce the difference spectra is comparable with that to enhance the activation of factor xii and prekallikrein , it appears that there is some correlation between the conformational change of hmw kininogen and the enhancement of the activation .
No activation of prekallikrein occurred in the absence of factor xii .
Consistent with this , we found that factor xii , but not factor xi , was activated and kallikrein was formed in blood from patients with systemic amyloidosis , a disease marked by the accumulation and deposition of misfolded plasma proteins .
An enzyme-linked immunosorbent assay ( elisa ) for the measurement of activated factor xii ( hageman factor ) in human plasma .
Furthermore , when the patients' plasma was treated with lpl , factor xii was activated promptly and substantially , whereas no similar effect was observed in the controls .
Contact activation factors in plasma from women using oral contraceptives--increased levels of factor xii , kinin-free high molecular weight kininogen and acetone-activated kallikrein .
The intrinsic coagulation pathway was studied by bringing a variety of biomaterials into contact with a plasma aliquot and observing the rate of clotting diminish by virtue of factor xii activation .
Such a relationship is based on studies that (1) establish a constant ratio of esterase activity on various synthetic substrates for the kaolin-activated arginine esterase , purified kallikreins , and preparations obtained during the fractionation procedure ; (2) exclude other known plasma and tissue arginine esterases ; (3) confirm the requirement for factor xii in the activation of the enzyme precursor ; and (4) show similarities in behavior between the plasma esterase and purified kallikreins toward a variety of inhibitors .
The apparent cooperativity of zn ( ii ) effects on factor xii fluorescence quenching and activation kinetics , and the apparent noncooperativity in zn ( ii ) binding to factor xii measured by equilibrium dialysis could be explained by a two-state model in which zn ( ii ) binding is linked to a conformational change in the protein .
These results show that the kallikrein-kinin system can be activated by factor xii , in a process separate from the coagulation cascade , and point to a protective role for factor xii following activation by misfolded protein aggregates .
Tests of haemostasis documented a slightly prolonged activated partial thromboplastin time ( aptt ) ( 45'' ) due to mild factor xii deficiency ( clotting activity 32% ) .
Factor vii activity ( viic ) , factor vii antigen ( viiag ) , prothrombin fragment 1+2 ( f12 ) , fibrinopeptide a ( fpa ) and fibrinogen were measured in all participants , and activated factor vii ( viia ) , factor ix activation peptide ( ix pep ) and factor x activation peptide ( x pep ) in a large sub-sample .
These studies show that the functional defect of prekallikrein zürich is due to an impaired cleavage by activated factor xii and probably the lack of enzymatic activity of the cleaved variant molecule .
Heritability and common household effect were estimated for plasma concentrations of prothrombin , factor (f) v , factor viii , factor (f) ix , fibrinogen , von willebrand factor ( vwf ) , antithrombin , protein c , protein s , protein z , protein z-dependent protease inhibitor ( zpi ) , fibrinopeptide a ( fpa ) , protein c activation peptide ( pcp ) , activated protein c-protein c inhibitor complex ( apc-pci ) , activated protein c-alpha1-antitrypsin complex ( apc-alpha1at ) , prothrombin fragment 1.2 ( f12 ) and d-dimer , using the variance component method in sequential oligo-genic linkage analysis routines ( solar ) .
Explicit constants for the dextran-sulfate-mediated activation and autoactivation of purified human factor xii ( hageman factor ) .
The kinetics of activation of factor xii was investigated and was in agreement with previous studies ; sulfatide promoted activation but phosphatidylserine , phosphatidylethanolamine , and phosphatidylcholine did not .
Treatment of plasma from either the bowfin or gar with glass beads under conditions previously shown to activate factor xii in the plasma of mammals and reptiles did not generate bradykinin .
The type iii collagen preparation did not activate factor xii and did not possess tissue factor activity , indicating that the surface itself was not procoagulant .
Collagen activation of platelet-associated factor xi has been proposed as a mechanism for initiating intrinsic clotting independent of factor xii .
In_vitro reconstitution experiments showed that anophensin inhibits activation of the kallikrein-kinin system by inhibiting the reciprocal activation of factor xii ( fxii ) and prekallikrein ( pk ) , and subsequent release of bradykinin .
The polyelectrolyte hydrogels do not deplete antithrombin iii from blood and there is no activation of factor xii according to an in_vitro kallikrein generation test .
In the presence of sulfatides , factor xii activation by kallikrein had its ph optimum at 6.3 and the rate constant increased considerably at lower ionic strength .
Thrombin ( thr ) , plasmin ( pl ) and elastase ( elp ) are serine proteinases which are quickly inactivated by their specific inhibitors ( at iii , alpha 2ap , alpha 1at ) , if intravascular activation of coagulation and fibrinolytic system or if release from pmn granulocytes by different stimuli ( fi , endotoxin , activated factor xii , ao ) occurs .
Xiiaa , a recently identified in_vivo form of activated factor xii is an independent indicator of long-term all-cause mortality in patients admitted with chest pain , providing prognostic information above and beyond conventional risk factors .
Hkh20 inhibited activation of prekallikrein when a mixture containing hk , prekallikrein and factor xii was incubated with dextran sulfate , gc1qr , amyloid beta or endothelial cells .
It is speculated that a factor appearing as a result of blood clotting is able to activate the classical pathway of complement in the cold ; it is probably not related to hageman factor ( factor xii ) , factor vii , thrombin , kallikrein .
Heparin at 1.6 and 16 usp u/ml was not able to produce activation , in contrast to dextran sulfate ( 20 micrograms/ml ) which supported activation of both factor xii and hk .
Using factor xiia ( activated hageman factor ) for activation normal prekallikrein levels were found in 2 of them whereas factor xii levels , however , were below normal .
In the asthma plasmas , these differences approach , but do not quite attain , significance ; (2) complexes of alpha 2m-kk potentiate prekallikrein activation in buffer ( ba ) and dextran sulfate activation ( dsa ) assays ; and (3) polybrene ( factor xii inhibitor ) induces an early blockage in the production of kallikrein activity in ba and dsa , indicating the presence in these plasmas of cryptic surfaces with a function analogous to dextran sulfate .
Possible reasons for this activation are an activation of the contact phase factor xii system and the release of tissue factor both from the ruptured plaque and from stimulated monocytes .
Similar kinetics of factor xi cleavage are seen when 40 nmol/l factor xiia ( equal to 10% of factor xii activation ) is added to factor xii-deficient plasma if an activating surface is provided .
A modified act using maximal activation of factor xii , max-act ( actalyke max-act ; array medical , somerville , nj ) , may be less variable and more closely related to heparin levels .
The assay system for factor xia was not significantly affected by the presence of plasma kallikrein , factor xiia , high-molecular-weight kininogen , amylose sulfate or sulfatide within the range of the amounts used for surface-mediated activation of factor xii , prekallikrein and factor xi .
In temperature studies , below 47 degrees c , the decrease in the activation rate was not related to the thermal denaturation of enzyme or substrate , nor to the choice of activator enzyme ( factor xiia or kallikrein ) , nor to the species of factor xii ( human or bovine ) but to a behavior , designated a thermal transition , associated with the surface or the protein-surface interaction .
Endothelial cells have a high-affinity receptor that binds either hmw kininogen or factor xii in a zinc-dependent interaction , and activation of factor xii can occur along this surface to initiate kinin formation .
In free solution kallikrein and the light chain were equally effective in activating factor xii and both enzymes had their ph optimum at ph 7.0 ( k1 = 16 x 10(3) m-1 s-1 ) .
The activation of plasma prekallikrein by single-chain factor xii has been studied in the presence of high molecular weight kininogen and kaolin .
One hundred and forty-two fasting men ( median age 36 years ) including 39 smokers , and 124 women ( median age 34 years ) including 35 smokers , were tested between 0800 h and 1000 h. fibrinogen correlated positively with white blood cells ( wbc ) ( r = 025 ) , prothrombin fragment 1.2 ( f12 ) ( r = 021 ) , cholesterol ( r = 027 ) , beta-thromboglobulin ( r = 029 ) , factor vii clotting activity ( fviic ) ( r = 027 ) ( all p < 00001 ) , tissue plasminogen activator antigen ( t-paag ) ( r = 022 , p < 00005 ) , plasminogen activator inhibitor-1 antigen ( pai-1ag ) ( r= 020 ) and vcam-1 ( r= 019 ) ( both p< 0002 ) .
Isolated cac promoted the generation of activated factor xi ( xia ) in a mixture containing purified factor xi , factor xii , and kaolin .
In the presence of prekallikrein , this assembly of factor xii and high-molecular-weight kininogen on vsmc leads to the activation of prekallikrein to kallikrein with a rapid formation of bradykinin .
This protein was expected to be the 'minimal' portion of factor xii able to sustain protease but unable to recognize substrates and surfaces necessary to activate the contact phase of coagulation .
The rate of activation of factor xii by alpha-kallikrein and beta-kallikrein was similar .
The effects of these two kinds of negatively-charged surfaces on the following three activation reactions were compared ; the activation of prekallikrein by factor xii ( reaction 1 ) , the activation of factor xii by kallikrein ( reaction 2 ) and the activation of prekallikrein by factor xiia ( reaction 3 ) .
This suppression was not only due to inhibition of factor xii activation but was also related to function of activated factor xii ( xiia ) .
The relationship between factor vii coagulant activity and factor xii activation induced in plasma by endogenous or exogenously added contact surface .
This indicates that blood collection in vacutainer or vacuette tubes induces a rapid activation of factor xii and factor xi .
Reconstitution experiments showed that triafestin-1 and triafestin-2 inhibit the activation of the kallikrein-kinin system by inhibiting the reciprocal activation of factor xii and prekallikrein , and subsequent release of bradykinin .
Previous experiments with rat plasma demonstrated that plasmin and also a plasmin-like factor without affinity for lysine-sepharose were able to destroy the capacity of hmwk to function as a cofactor in the surface-dependent activation of factor xii , without a corresponding release of kinin .
This is demonstrated in the present study , for the autolytic activation of factor xii in the presence of a contact activator and an irreversible inhibitor of factor xiia .
Direct binding assays demonstrated that this inhibitory effect is due to hamadarin binding to both factor xii and high molecular weight kininogen and interference in their association with the activating surface .
Frequently , the first indication of an additional factor xii deficiency is the disproportionate prolongation of the activated partial thromboplastin time ( ptt ) as regards the factor viii level .
Prothrombin time ( pt ) ; activated partial thromboplastin time ( aptt ) ; thrombin time ; antithrombin iii ; protein c ; protein s ; von willebrand factor antigen ; ristocetin cofactor ; plasminogen-alpha(2) -antiplasmin ; the coagulation factors fibrinogen , factor (f) ii , fv , fvii , viii , f ix , fx , fxi , fxii , fxiii , and activated factor xii ( fxiia ) ; d-dimer ; fibrin monomer ; thrombin-antithrombin complex ; prothrombin fragment 1 + 2 ( f1+2 ) ; plasmin-alpha(2) -antiplasmin complexes ( paps ) ; and platelet factor 4. the fvii activity ratio was assayed to quantify activation of fvii .
This study indicates that heparinized plasma does not support activation of the contact system mediated through activation of factor xii .
Our results also indicate that factor xi can be activated by thrombin in the absence of factor xii and that the function of factor xi is simply to enhance conversion of factor ix to factor ixa resulting in enhanced thrombin generation on the platelet surface .
Analysis of the increase in fibrinolytic activity revealed no demonstrable activation of intrinsic systems via factor xii , nor changes in plasminogen , prekallikrein and c1-inactivator .
Negatively charged surfaces may activate factor xii and the prekallikrein-kinin cascade , resulting in bradykinin ( bk ) production .
In the absence of sulfatides , kallikrein and the light chain were equally effective in factor xii activation ( k1 = 157 x 10(3) m-1 s-1 at ph 70 ) .
No clear evidence for a role of tissue factor expression by monocytes , factor xii or insulin in postprandial fvii activation was observed .
Activation of hageman factor ( factor xii ) upon exposure to negatively charged agents has been attributed to proteolytic cleavage of this molecule .
The recombinant protein of larger size was identified as the full-length factor xii of 80 kda and its specific activities and activation patterns , determined both by the coagulation and the amidolytic assays , are very similar to these of native human factor xii .
In_situ ellipsometry suggested that ti is an intrinsic coagulation activator in_vitro , since significant amounts of factor xii ( f xii ) and high molecular weight kininogen ( hmwk ) were found on the surfaces after 1 min incubation in heparin plasma .
A chromogenic peptide substrate assay for hk ( hkcs ) has been developed in which test plasmas are mixed with diluted hk-deficient plasma and incubated with a soluble contact system activator that activates prekallikrein and factor xii .
Therefore , we looked for alterations of fibrinolytic parameters ( tissue plasminogen activator ( t-pa ) , tissue plasminogen activator inhibitor ( pai ) , d-dimer , euglobulin-clot-lysis-time ( eclt ) , plasminogen , alpha 2-antiplasmin ) and of some coagulation parameters ( prothrombin time , fibrinogen , platelets , antithrombin iii , protein c , factor xii ) in clearly defined septic patients and for the relations of these values to the severity of the disease ( apache ii-score ) .
Activation of kalliklein and dekinination of high-molecular kininogene occurred after the interaction between proenzymes of contact phase of blood coagulation ( factor xii , prekallikreins , high-molecular kininogene ) .
Ten patients with familial lipoprotein-lipase ( lpl ) deficiency and 10 healthy control subjects were therefore compared to explore the hypothesis that high concentrations of unesterified fatty acids ( ufa ) , released from triglyceride-rich lipoproteins by lpl , are a source of factor xii activation and hence the increased viic that is observed post-prandially and in non-lpl-deficient hypertriglyceridaemic states .
Prekallikrein activation , c1 esterase inhibitor , and factor xii as predictors of adverse reaction to contrast media. a prospective study .
This confirms the inhibitory effect of beta 2-gp-i on the contact activation and shows that inhibition is effective on the autoactivation of factor xii in plasma .
The lesion in the gallbladder consists of intense injury of blood vessels in the muscularis and serosa similar to those induced experimentally by in_vivo activation of factor xii dependent pathways .
Hypotensive effect of the active fragment derived from factor xii is mediated by an activation of the plasma kallikrein-kinin system .
Dextran sulphate of mr 500,000 ( ds500 ) and 50,000 ( ds50 ) was able to initiate contact system activation in plasma ( determined by measuring the amount of factor xiia-c1-inhibitor , kallikrein-c1-inhibitor and factor xia-c1-inhibitor complexes generated ) as well as to support factor xii autoactivation and to enhance factor xii susceptibility for cleavage by kallikrein ( as measured with amidolytic assays using purified proteins ) .
The concave upward curve due to an autocatalytic activation was not observed even after the addition of factor xiia to factor xii preparation .
At the same time points , haemostatic system activation was investigated by measuring prothrombin fragment f1.2 ( f12 ) and thrombin antithrombin complexes ( tat ) in venous blood and in blood emerging from a skin incision ( shed blood ) .
The generation of the arginine esterase activity by chloroform and ellagic acid was apparently dependent on the activation of factor xii , being blocked by polybrene .
All three serotonin antagonists showed a serotonin-like lowering effect on the activation of factor xii and on the level of prekallikrein in plasma ( bol 148 10-40 mg/kg ; methysergide 010-060 mg/kg ; ergotamine 010-060 mg/kg ) .
Plasma levels of plasminogen activator inhibitor type 1 ( pai-1 ) , tissue-type plasminogen activator ( t-pa ) , fibrinogen , thrombin-antithrombin ( tat ) complexes , and prothrombin fragments ( f12 ) were measured at baseline and after standardized venous occlusion ( vo ) in patients with pph ( 24 female , 9 male ) .
Potential-mediated and time-controlled first order activation of factor xii ( hageman factor ) adsorbed to carbon surfaces .
A case-control study of 260 cases of stable heart disease from the irish component of the european action on secondary prevention through intervention to reduce events ( euroaspire ) ii cohort and 260 age , sex-matched controls. c-reactive protein , homocysteine , cysteine , von willebrand factor , activated factor xii and conventional risk factors were assayed or recorded .
Two clinically healthy cats who were conspicuous pre-operative because of a distinctly prolonged , activated partial thromboplastin time showed a decreased factor xii activity .
Both gel types induced elevated levels of contact activation of bound , but not plasma-phase factor xii relative to controls .
One of the latter is lost when factor xii is activated to alpha-factor xiia .
The kaolin-mediated reciprocal activation of bovine factor xii and prekallikrein was divided into the following two reactions :
We assessed relationships between c-reactive protein , homocysteine , cysteine , von willebrand factor , activated factor xii and stable heart disease , as well as interaction with established risk factors .
In a double-blind , randomized , cross-over study the neutralizing action of protamine towards unfractionated heparin ( ufh , 150 u/kg iv ) and a low molecular weight heparin ( lmwh , fragmin , 100 anti-xa u/kg iv ) was investigated in 15 healthy subjects in_vitro by measuring activated partial thromboplastin time ( aptt ) , thrombin time ( tt ) and anti factor xa activity ( anti-xa ) in venous blood and in_vivo by determination of prothrombin fragment 1.2 ( f12 ) and thrombin-antithrombin iii complexes ( tat ) in venous blood and in shed blood .
Measurement was made of the contact and intrinsic coagulation system proteins factor xii , activated factor xii and prekallikrein and the protease inhibitors antithrombin iii , heparin co-factor ii , alpha 2-macroglobulin and c1-esterase inhibitor .
The activated partial thromboplastin time of the patient was corrected by addition of normal , factor xii deficient or fletcher plasma , but not corrected by fitzgerald or williams plasma .
Thus , reciprocal activation is the predominant mode of factor xii activation in normal plasma .
Kaolin thus induces a clear and reproducible writing reaction , which might be mainly dependent on the action of bradykinin via activation of factor xii , and should prove to be a simple and convenient model of bradykinin-induced pain for the assessment of analgesic actions .
We attempted to identify this portion and its position in the three pathways ( extrinsic , intrinsic factor xii dependent , and intrinsic factor xii independent ) of plasminogen activator activity that have been defined in the defs of plasma .
In this paper , coagulation factors related to contact activation , such as factor xii ( fxii ) , factor xi ( fxi ) , prekallikrein ( pk ) , high molecular weight kininogen ( hmwkg ) , and kinins were measured in 15 cases of nephrotic syndrome , and clinical significance of these results were discussed .
Activation of the cascade by abeta ( 1-38 ) was dependent upon its preincubation time in buffer , suggesting that aggregation of abeta is required , and studies with abeta ( 1-40 ) revealed time-dependent aggregation by microscopy and augmented zinc-dependent binding of both factor xii and hk to aggregated abeta .
Previous studies from our laboratories ( sugo et al ( 1980 ) biochemistry 19 , 3215-3220 ) have shown that bovine high-molecular-weight ( hmw ) kininogen remarkably accelerates the kaolin-mediated activation of factor xii in the presence of prekallikrein , and that both fragment 1.2 and the light chain regions located in the cooh terminal half of the kininogen molecule are essential for the activation .
Since the effects of ph and ionic strength on sulfatide-dependent factor xii activation by kallikrein can be explained by effects on kallikrein binding to sulfatides we conclude that surface-bound factor xii is activated by surface-bound kallikrein .
We have suspected that bradykinin , a strong vasodilator generated through the activation of factor xii , prekallikrein , and high molecular weight kininogen was removed by ultrafiltration .
[effect of lysozyme suppression of factor xii activation on postadrenaline hypercoagulation]
The cause , although not yet clearly defined , is believed to be related to bile stasis , ischemia , bacterial infection , sepsis , the activation of factor xii , and the shwarzman reaction .
One of these loop regions is highly mobile despite being anchored by the disulphide bridge which is characteristic of a small subset of serine proteases namely tissuetype plasminogen activator , factor xii and complement factor i .
Generation of thrombin was measured by enzyme-linked immunosorbent assay ( elisa ) as plasma levels of the prothrombin fragment 1 + 2 ( f1 + 2 ) ; the initiators of the tissue factor and contact coagulation pathways were investigated by measuring plasma levels of activated factor vii ( fviia ) coagulometrically and activated factor xii ( fxiia ) by elisa .
Inhibition of the activation of hageman factor ( factor xii ) by human vascular endothelial cell culture supernates .
Inhibition of endogenous kinin-releasing mechanisms by administration of hexadimethrine , a recognized inhibitor of the activation of clotting factor xii , and depletion of kininogen by administration of carrageenin blocked collagenase-induced oedema .
In our study we found that in the absence of factor xii , pk is not activated .
Activation of human factor vii in plasma and in purified systems : roles of activated factor ix , kallikrein , and activated factor xii .
The increased hmwfd concentration may reflect activation of the coagulation system not mediated by factor xii activation nor potentiated by decreased antithrombin iii .
Plasmin-mediated ( 025 mumol/l ) activation of purified factor xii occurred in 0.05 mol/l tris-hcl and 0.012 mol/l nacl ( ph 78 ) at 37 degrees c , resulting in equimolar quantities of two fragments that corresponded to cleavage of factor xii at arg353-val354 , the site involved in kallikrein-mediated activation of factor xii , and cleavage at lys346-ser347 , an apparently novel site of plasmin-mediated hydrolysis of factor xii .
Nsaid do not interfere with factor xii activation and increase the severity and risks of microthrombosis by inhibiting synthesis and release of protective prostaglandins .
We conclude that reconstituted collagen is not capable of activating factor xii .
For this purpose xiia , factor ix activation peptide ( ixp ) , viia , prothrombin fragment 1 + 2 ( f1 + 2 ) , and thrombin-antithrombin complex ( tat ) were determined in plasma samples taken before and 3 , 6 , and 9 hours after intake of a mixed meal type of oral fat load in 24 healthy men the viia response to fat intake was also determined in 7 patients with single coagulation-factor deficiency , of whom 2 were deficient in factor xii , 2 in factor xi , and 3 in factor ix .
At timed intervals prothrombin activation fragment 1.2 ( f12 ) levels ( thrombin generation ) were measured using an elisa technique .
Sac i inhibited activated human factor xii and human plasma kallikrein .
C1 inhibitor ( c1 inh ) is the major inhibitor of the proteolytically active subcomponents of c1 , kallikrein , activated forms of factor xii , and factor xia in plasma .
In view of the results of the blood studies after implantation coagulation activation in endogenous and exogenous system ( aptt and pt ) , and increase in activity of factor xii and vii .
Lactic acidosis can activate c5 from the complement system and factor xii from the contact system directly , even in the absence of cellular components .
We evaluated each subject's hemostatic factors , including factor vii , factor xii , thrombin-antithrombin iii complex ( tat ) , fibrinogen , plasmin-antiplasmin complex ( pic ) , plasminogen activator inhibitor ( pai-1 ) , and d-dimer .
Molecular mechanisms of surface-dependent activation of hageman factor ( factor xii ) .
Addition of 131i-hmw kininogen and 125i-factor xii or 131i-hmw kininogen and 125i-prekallikrein to normal plasma followed by activation with dextran sulfate and analysis on sds gels indicated that the observed cleavage of prekallikrein and hmw kininogen is fast compared to the observed cleavage of factor xii , which is much slower and less extensive .
The presence in cigarette smoke of material that is both allergenic and capable of activating factor xii of the intrinsic pathway of coagulatin may be important to the pathogenesis of cardiovascular and pulmonary disease associated with cigarette smoking .
This assay is based on the property of glass-bound factor xii to activate prekallikrein ( pk ) into kallikrein in factor xii-deficient plasma , which is assessed by measuring the formation of kallikrein-c1-inhibitor complexes in this plasma by radioimmunoassay .
The phenomenon of the vroman effect is explained by the mechanism of surface-dependent activation of factor xii , which both directly and indirectly ( through the formation of kallikrein ) generates hka from hk .
Effect of kallikrein-kinin system activation by factor xii f pretreatment on experimental hemorrhagic shock .
Kks signaling cascade is activated by activated factor xii ( fxiia , hageman factor ) - and prolylcarboxypeptidase ( prcp ) -dependent pathways on endothelial cells .
It is suggested that the inhibition of platelet aggregation is due to the anaphylactic activation of factor xii and this mechanism may be of importance in rat anaphylaxis .
The effect of chemical modification of basic amino acid residues on the activation and amidolytic activity of hageman factor ( factor xii ) .
The optimum ph for light-chain-dependent factor xii activation in the presence of sulfatides remained unaltered and the reaction was not affected by the ionic strength .
Based on these results we propose that a conformational change in factor xii is a key event in the activation process of this molecule .
The prekallikrein and high-molecular-weight kininogen levels were sufficient for activation of factor xii .
D-dimer and prothrombin activation peptide ( f12 ) levels increased in a similar pattern for both groups during and after cpb .
Endothelial cells express a matrix protein which binds activated factor xii in a zinc-independent manner .
The mechanism by which negatively charged substances such as celite , kaolin , or ellagic acid contribute to the surface-dependent activation of hageman factor ( factor xii ) was studied .
Coagulation of human blood by b. anthracis required secreted zinc metalloprotease inha1 , which activated prothrombin and factor x directly ( not via factor xii or tissue factor pathways ) .
The reactions of reciprocal activation , consisting of activation of factor xii by kallikrein and of prekallikrein by activated factor xii , follow michaelis-menten kinetics ; values of kcat and km for each of these reactions were determined in the presence of dextran sulfate and in its absence .
It is proposed that binding of these antibodies to factor xii blocks interaction of the positively charged region between residues 5 and 15 with negatively charged surfaces , thereby inhibiting activation .
The relationship between extrinsic coagulation factors , tissue factor pathway inhibitor ( tfpi ) and activated factor xii ( fxiia ) was examined in 71 patients with end-stage chronic renal failure .
The washed platelets before and after aggregation by adp , thrombin or collagen did not show any ability to trigger or accelerate the activation of factor xii and prekallikrein .
Patients with unstable angina pectoris had a moderate procoagulant state , especially a contact phase activation compared with age-matched controls ( factor xii 939 +/- 56 versus 1128 +/- 54% ; p < 005 ; high molecular weight kininogen 553 +/- 54 versus 861 +/- 65% ; p < 001 ) .
The possible involvement of plasma kallikrein and factor xii , activators of the kallikrein-kininogen-kinin system , were evaluated through analysis of gene expression in endometrial and conceptus tissues .
Thrombolytic therapy activates the contact system , and factor xii activation may activate the coagulation cascade and inflammation .
Plasmatic prekallikrein , c1-inhibitor , alpha 2-macroglobulin , activated partial thromboplastin time , prothrombin time , factor xii , factor xi , factor v and prealbumin were measured .
Immunohistochemical labeling for von willebrand factor , tissue factor , factor xii , tissue factor pathway inhibitor , thrombomodulin , protein c , protein s and prothrombin activation fragment f1 + 2 was performed .
This dual effect on venous thrombosis is a consequence of two actions , one that inhibits thrombin and factor xa and one that induces factor xii activation .
Circulating anticoagulant activity that had at least two distinct mechanisms--one directed against factor xii and one directed against blood thromboplastin ( prothrombin activator complex ) --developed in a patient with clinical and laboratory evidence of procainamide hydrochloride-induced systemic lupus erythematosus .
Here we report on the relationships of c4a and c3a ( complement activation products ) , of factor xii and prekallikrein ( contact system proteins ) , of elastase ( a protease released by activated neutrophils ) and of the cytokine il-6 to hemodynamic and biochemical parameters measured in those 48 patients at the time of admission to the intensive care unit .
Kallikrein generated on the surface of endothelial cell is capable of activating factor xii .
The complement system is activated whereas serum kallikrein does not alter , suggesting that platelets rather than factor xii are crucial in contact activation .
Heat shock protein 90 catalyzes activation of the prekallikrein-kininogen complex in the absence of factor xii .
Activation of the intrinsic pathway could not be detected by a series of measurements of the plasma levels of factor xii , prekallikrein , factor xiia-c1 inhibitor complexes , kallikrein-c1 inhibitor complexes , and the activation peptide of factor ix .
We have shown that bovine hmw kininogen remarkably accelerates the activation of factor xii and prekallikrein in the presence of kaolin , adsorbing on kaolin through the fragment 1.2 region and forming a complex with prekallikrein through the light chain region ( sugo et al , 1980 ; ikari et al , 1981 ) .
This procedure was sensitive to approximately 0.3 ng of either factor xii or prekallikrein antigen and was useful for detection of factor xii cleavage fragments in contact activated plasma .
Thus cold-promoted activation of prorenin depends on the presence of factor xii and prekallikrein , whereas the other clotting factors are not essential .
Hageman factor ( hf , factor xii ) , adsorbed to negatively charged agents , is transformed to an activated state in which it initiates reactions of the intrinsic pathway of thrombin formation by activating plasma thromboplastin antecedent ( pta , factor xi ) .
At approximately 5 kda , the sulfated galactan fragment had no effect on factor xii activation , and showed the same effect as unfractionated heparin in a venous thrombosis model .
These include hypoplasminogenemia , decreases in plasminogen activator , increases in plasminogen activator inhibitor , and factor xii deficiency .
Although clofibrate treatment of the type ii patients did not change plasma lipids , it decreased intravascular coagulation , apparently via decreased factor xii activation and stimulation of fibrinolysis .
Studies of adsorption , activation , and inhibition of factor xii on immobilized heparin .
Thrombin generation and activation of fibrinolysis were found to occur in uraemic patients , as substantiated by increased plasma levels of markers for thrombin generation ( prothrombin fragment f12 and thrombin-antithrombin complex ) and fibrinolysis ( d-dimer and plasmin-antiplasmin complex ) , respectively .
The analysis of normal human plasma by fibrin autography revealed four species of plasminogen activator ( pa ) activity related to tissue-type pa , factor xii , prekallikrein and urokinase-type pa ( u-pa ) .
Furthermore , they interact with both the n-terminus of factor xii and domain d5 of high molecular weight kininogen , which are the binding domains for biological activating surfaces .
High doses of amcha ( 200 mg/kg ) did not inhibit these effects , but significantly increased the lowering caused by dextran of the capacity of high molecular weight kininogen ( hmwk ) to function as a cofactor in the activation of factor xii .
Dextran injected intravenously into rats causes a rapid lowering of the extent of activation of factor xii and of the plasma levels of prekallikrein and plasminogen , and at the same time a profound fall in blood pressure .
However , solution conditions were identified that allowed the following negatively charged surfaces to function , in nearly equal potency , in the activation of factor xii : .
This effect of kallikrein on the cleavage of factor xii bound to moab f1 was specific because the fibrinolytic enzymes plasmin , urokinase , and tissue-type plasminogen activator could not substitute for kallikrein .
Inhibition of the activation of hageman factor ( factor xii ) by platelet factor 4 .
Effect of heparin on the activation of factor xii and the contact system in plasma .
Involvement of the contact system of coagulation in the pathogenesis of various inflammatory diseases is suggested by reduced plasma levels of factor xii ( hageman factor ) and prekallikrein generally considered to result from activation of the contact system .
The secondary structure of human hageman factor ( factor xii ) and its alteration by activating agents .
The lower yield of pka-activity in acetone/kaolin-activated rcpl-p , as compared with activated rcpl , seems to be due to the absence of a factor of significance for the activation of factor xii , which is not plasmin , plasma kallikrein , or high molecular weight kininogen .
Thrombin activates factor xi on activated platelets in the absence of factor xii .
In the presence of dextran sulfate , the catalytic efficiency for factor xii activation was increased 11 000-fold , and that for prekallikrein was increased 70-fold .
The effect of hmw kininogen upon the amidolytic properties of two species of activated hf ( factor xii ) , designated hfea and hff , was studied by using the synthetic substrate s2238 .
Activation of these two pathways was unexpectedly linked and dependent on fluid-phase activation of factor xii .
Cat data of 40 patients with chd ( age range from newborn to 18 years ) were compared to data using standard coagulation parameters such as prothrombin ( fii ) , antithrombin ( at ) , tissue factor pathway inhibitor ( tfpi ) , prothrombin fragment 1.2 ( f 12 ) , thrombin-antithrombin ( tat ) , activated partial thromboplastin time ( aptt ) , and prothrombin time ( pt ) .
Reconstitution experiments showed that hamadarin inhibits activation of the plasma contact system by inhibition of the reciprocal activation of factor xii and kallikrein .
However , in a very sensitive test for factor xii activation ( contact promoted shortening of the thrombotest ) a slight activation of this factor was observed .
Thus , the plasma kallikrein/kinin system has two mechanisms for its activation : one that is dependent and another independent of factor xii .
Global coagulation parameters , coagulation factors ( factor v : c , factor viii : c , activated factor xii , and factor xiii ) and markers of thrombin generation ( f1+2 fibrin split products , thrombin-antithrombin complexes ) , fibrin generation ( fibrinogen and fibrin degradation products ) , and fibrinolysis ( d-dimers , thrombin degradation products , plasminogen ) were determined .
Thus , sulfatide-dependent activation of purified factor xii is not due to contaminating proteases and is described by a second order mechanism of autoactivation due to the action of surface-bound factor xiia on surface-bound factor xii .
We interpret the results to indicate that the negatively charged surface provided by ds accelerates in plasma the autoactivation of factor xii and the activation of prekallikrein , resulting in an increase of the effective concentration of kallikrein and possibly other proteases and proteolysis of ldl-apob-100 .
The kit consists of 1 ) a prekallikrein activator of the cephalin-ellagic acid type containing factor xii and hmw-kininogen to ensure a total activation of the prekallikrein even in pathological plasmas , 2 ) a buffer which is optimal for both activation and substrate hydrolysis and 3 ) the chromogenic substrate s-2302. a control plasma is also included .
Prothrombin activation was measured by prothrombin fragment 1.2 ( f12 ) formation .
Therefore , these findings point to the existence of multiple mechanisms of activation of factor xii .
The role of prekallikrein and high-molecular-weight kininogen in the contact activation of hageman factor ( factor xii ) by sulfatides and other agents .
Fibronectin type i domains from homologous proteases factor xii , hepatocyte growth factor activator and from the extracellular matrix protein fibronectin also bound to aggregated amyloidogenic peptides .
Kinetic constants of factor beta-xiia ( factor xii fragment ) for these substrates and for n-benzol-l-isoleusyl-l-glutamyl-glycyl-l-arginine-p-nitro ani lide ( s-2222 ) were determined , and they allowed the assessment of the contribution of this factor to this assay and its estimation in the activated phase .
Our data suggest that sulfatides stimulate kallikrein-dependent factor xii activation by two distinct mechanisms :
However , there were no effects of gemfibrozil treatment on the plasma concentrations of fibrinogen , factor vii antigen , activated factor vii ( viia ) or activated factor xii ( xiia ) , or on fibrin gel structure .
Tissue plasminogen activator antigen , plasminogen activator inhibitor-1 , plasminogen , and fibrin fragment d-dimer as well as a marker of coagulation activation ( prothrombin fragment f12 ) .
However , the accelerating effect of hmw kininogen on the activation of factor xii by plasma kallikrein was very weak , when amylose sulfate or sulfatide was used as surface .
Subsequent correction studies , utilizing activated partial thromboplastin time , confirmed factor xii deficiency .
However , taking the low physiological concentration of urokinase into account , the efficiency of activated factor xii is equivalent to that of urokinase .
Determination of the minimal concentrations of contact activation factors in deficient substrate plasmas required to assess accurately factor xii , factor xi , factor ix , and high molecular weight kininogen .
(1) plasma concentrations of prothrombin ; (2) plasma inhibition of 125i-alpha-thrombin ; and (3) four biochemical markers of in_vivo thrombin activation ( thrombin complexed to its inhibitor antithrombin iii [atiii ; tat] , prothrombin fragment 1.2 ( f12 ) , activated protein c complexed to the inhibitors alpha 1 antitrypsin [apcat] ) , and protein c inhibitor ( apc-pci ) .
Results : hereditary angioedema plasma demonstrated augmented factor xii activation , production of factor xiif , prekallikrein activation , and high-molecular-weight kininogen cleavage , and , as a result , bradykinin formation was markedly increased .
The monoclonal antibodies ( 2-1 , 4-1 , 7-1 and 10-1 ) consisted of igg1. 4-1 inhibited the activation of f.xi completely in the presence of high molecular weight kininogen and kaolin and the others did so partially , whereas these antibodies had no effect on the activation of f.xi with activated factor xii ( beta-xiia ) .
Activation of the intrinsic coagulation pathway was evaluated by measurements of factor xii , prekallikrein , and kallikrein inhibitors .
Homologous type i and ii repeats are known to occur in tissue plasminogen activator , factor xii and a bovine seminal plasma protein .
Specifically , this review will reconsider the concept of the reciprocal activation of the proteases of the contact phase of coagulation , factor xii , and prekallikrein , in light of much recent evidence indicating that factor xii , itself , autoactivates when associated with negatively charged surfaces .
The systemic inflammatory response , triggered by contact activation of factor xii , produces functional disturbance in vital organs , notably the brain and lung .
Incubation of plasminogen-free rat citrated plasma with acetone ( 23% v/v ) yielded enzyme preparations with high levels of plasminogen activator ( pga ) and kininogenase ( kallikrein ) , but with a low concentration of high molecular weight kininogen ( hmwk ) active as cofactor for kaolin-induced activation of factor xii .
The objective of our study was to investigate the prevalence of the polymorphisms factor v leiden ( fvl ) , prothrombin g20210a ( pt g20210a ) , methylenetetrahydrofolate reductase c677t ( mthfr c677t ) , plasminogen activator inhibitor type 1 -675 4g/5g ( pai-1 4g/5g ) and factor xii -4 c/t ( fxii -4 c/t ) in 295 slovenian patients with venous thrombosis ( vt ) and 223 healthy controls in order to establish their contribution to the risk for vt .
Estrogen induction and contact phase activation of human factor xii .
Sds-polyacrylamide gel electrophoresis and autoradiography of cell-bound 125i-fxii showed that factor xii underwent limited proteolysis and the molecular weights of the fragments were similar in size to activated fxii .
The effect of venous occlusion on the elt and on the activation of factor xii was considerably increased when heparin or sp 54 was injected 2 h prior to the test .
Intravenous injection of bromelain , which was previously reported to produce prolonged hypotension through the activation of factor xii to release bradykinin , induced slight effect in katholiek rat , while in kitasato rat it showed prolonged hypotension in similar degree as sd rat .
In contrast to previously reported studies , no evidence could be adduced for the activation of hageman factor ( factor xii ) by platelets , whether or not these cells had been incubated with adenosine diphosphate ( adp ) .
The present study provides evidence that one action of aprotinin is inhibition of the activation of hageman factor ( factor xii ) .
Adding 1 mumol/l alpha-thrombin ( equivalent to 50% prothrombin activation ) directly to factor xii deficient or normal plasma ( with or without kaolin/cephalin/ca2+ or dextran sulfate ) led to instantaneous fibrinogen cleavage , but again no cleavage of factor xi was observable .
High molecular weight kininogen ( hmw ) -kininogen , the cofactor of contact-activated blood coagulation , accelerates the activation of factor xii , prekallikrein , and factor xi on a negatively charged surface .
During cardiopulmonary bypass ( cpb ) , contact-phase activation of factor xii , prekallikrein , and high molecular weight kininogen initiates the intrinsic pathway of coagulation .
Although most coagulation enzymes cannot be measured specifically and accurately , assays for activated factor xii and factor vii have recently become available .
Once before surgery , daily during hospitalization , and weekly after discharge we assessed platelet function , measured prothrombin activation fragment 1.2 ( f12 ) and plasminogen activator inhibitor-1 ( pai-1 ) concentrations , and evaluated aspirin hyporesponsiveness by whole-blood aggregometry and thromboelastography .
The quenching also did not involve the factor xii-dependent activities ; it was quantitatively normal in plasma with hageman ( n = 3 ) and fletcher ( n = 2 ) traits , and auk did not interfere with the generation of factor xii-dependent fibrinolytic activity by addition of purified activated factor xii in plasma with hageman trait .
In another group of rats , dextran sulfate ( 025 mg iv ) , which activates factor xii and thereby the conversion of prekallikrein to kallikrein , induced a short-lasting fall in blood pressure. 15 min after administration of dextran sulfate , plasma prekallikrein activity was almost completely suppressed .
The mechanism of kaolin-mediated activation of bovine factor xii was studied in the presence of prekallikrein and hmw kininogen .
The present study was undertaken to examine the role of hmw kininogen in the activation of factor xii and prekallikrein with other negatively-charged surfaces .
1 ) levels of polymorphonuclear ( pmn ) -elastase protein were markedly elevated in 6 of 6 patients and 10 of 11 parents tested , and levels were higher in homozygotes than in heterozygotes. 2 ) hereditary factor xii deficiency was found in 3 of 6 patients tested. 3 ) c1-inhibitor was elevated in 2 of 4 patients , prekallikrein was elevated in 1 of 4 patients , and plasminogen activator inhibitor type 1 was elevated in 1 of 4 patients .
Kinetic studies on surface-mediated activation of bovine factor xii and prekallikrein .effects of kaolin and high-mr kininogen on the activation reactions .
A mosquito salivary protein inhibits activation of the plasma contact system by binding to factor xii and high molecular weight kininogen .
The generation of bradykinin by contact activation requires autoactivation of factor xii ( hageman factor ) upon initiating surfaces , conversion of prekallikrein to kallikrein , and digestion of high-molecular-weight ( hmw ) kininogen .
Determination of contact phase activation by the measurement of the activity of supernatant and membrane surface-adsorbed factor xii ( fxii ) :its relevance as a useful parameter for the in_vitro assessment of haemodialysis membranes .
Recent evidence suggests that the gc1qr also serves as the zn(++) -dependent endothelial cell binding site for factor xii and high-molecular-weight kininogen , and activates intrinsic coagulation and kinin pathways in purified systems .
Inhibition of the activation of hageman factor ( factor xii ) and of platelet aggregation by extracts of brugia malayi microfilariae .
A common neoepitope is created when the reactive center of c1-inhibitor is cleaved by plasma kallikrein , activated factor xii fragment , c1 esterase , or neutrophil elastase .
The zn ( ii ) concentration dependence of factor xii fluorescence quenching was sigmoid and paralleled the zn ( ii ) -accelerating effect of factor xii activation by kallikrein and factor xiia , indicating that the spectral change was reporting zn ( ii ) -factor xii interactions responsible for the enhanced activation rate .
Catalysis along the cell surface requires zinc-dependent binding of factor xii and high-molecular-weight kininogen to proteins , such as the receptor for the globular heads of the c1q subcomponent of complement , cytokeratin 1 , and urokinase plasminogen activator receptor .
Compared to patients with normal fibrinogen ( n = 360 ) patients with hf had significantly elevated markers of activation of coagulation ( tat , f12 , fpa ) and fibrinolysis ( d-dimer , fdp ) indicating that disseminated intravascular coagulation/hyperfibrinolysis was the cause of hypofibrinogenemia .
Plasma kinin formation after in_vitro activation of factor xii in the coagulation system was examined in 4 patients with hereditary angioneurotic edema .
The prekallikrein activator in antihemophilic factor preparations was formed during contact with glass , and its behavior led to the conclusion that these concentrates contained hageman factor ( factor xii ) .
We investigated the capability of dextran sulphate ( ds ) of different molecular weights to initiate contact system activation in normal human plasma , and compared this with their capability to support factor xii autoactivation and to enhance factor xii susceptibility for cleavage by kallikrein .
Finally , prothrombin ( 12 microm ) and cacl2 ( 2 mm ) could substitute for hk ( 45 nm ) and zncl2 ( 25 microm ) in promoting optimal rates of thrombin-catalyzed factor xi activation on the platelet surface , thereby initiating the intrinsic coagulation pathway by mechanisms completely independent of the contact phase proteins , factor xii , hk , and prekallikrein .
Dic in these shock patients , accompanied by a decrease in pk , probably was mediated via factor xii activation .
For example , human pmel17 has important roles in the biosynthesis of the pigment melanin , and the factor xii protein of the hemostatic system is activated by amyloid .
Changes in tissue factor and activated factor xii following an acute myocardial infarction were uninfluenced by high doses of n-3 polyunsaturated fatty acids .
We investigated the effects of amyloid precursor protein isoforms on activated hageman factor ( factor xii ) , activated factor x ( stuart factor ) , and thrombin .
The partially purified platelet factor xi ( pt-xi ) could be activated by activated factor xii generated in_situ from single chain factor xi in a reaction requiring high molecular weight kininogen ( hmwk ) and a surface .
In this connection the activation of factor xii by et and the activation of the intrinsic system of coagulation due to it are discussed , the mechanism of blood platelet damage with subsequent thrombocytopenia is dealt with , and the induction for liberating of a thromboplastin-like procoagulant from leukocytes as well as the factors influencing this liberation are described .
These results suggested that map kinase signaling , activated by air-liquid interface , was , at least in part , related to cell differentiation in gsm06 cells induced by air-liquid interface .
The unwashed drainage blood contained high levels of procoagulation material and induced an activation of the plasma coagulation pathway with renewed clot formation and fibrinolysis in the patients .
These data suggest that rhuifn-gamma may stimulate the expression of another plasminogen activator inhibitor.
However , this accelerating effect of hmw kininogen on the amylose sulfate - and sulfatide-mediated activations ( reaction 1 ) was diminished after treatment with fluorescein iso-thiocyanate , whereas the effect on the kaolin-mediated activation was not influenced by fluorescein-labeling .
Thrombin-dependent activation of factor xi is an integral part of the revised theoretical model of coagulation in which coagulation is initiated by the extrinsic pathway and maintained by thrombin-induced activation of clotting factors v , viii , and xi .
However , since the enzyme responsible for the activation of pkrn-hk is fxiia , the levels of generated krn are positively related to the concentration of substrate .
When assembled on these proteins , prekallikrein becomes activated to kallikrein by the membrane-expressed enzyme prolylcarboxypeptidase ( prcp ) .
On the basis of facts known up till now special attention is devoted to the role of the thromboplastin-like procoagulant and the activation of the extrinsic system caused by it in developing a dic syndrome .
Inositolphospholipid-accelerated activation of prekallikrein by alpha-factor xiia was determined by measuring the appearance of kallikrein amidolytic activity towards the chromogenic substrate , d-prolyl-phenylalanyl-arginyl p-nitroanilide ( s-2302 ) .
During cardiopulmonary bypass , blood contact with the large nonendothelial surfaces of the extracorporeal circuit induces activation and consumption of platelets and plasma coagulation factors .
Thus , the goals of this study were to define how fibrinolysis is modulated in human plasma by contact or tissue factor ( tf ) activation , and what role tafi and fxiii plays in this system .
Known natural activators of fxii and the contact system include heparin , sulfatides , phospholipids , endotoxin , and urate crystals .
The increased plasminogen activator inhibitor activity is associated with the metabolic syndrome and constitutes an ( in part genetically determined ) disturbance in patients with stable or unstable coronary heart disease .
Inverse associations with bmi were seen for tissue plasminogen activator activity and activated protein c ratio .
We then studied the effect of other heparin-like anticoagulants on the thrombin-mediated factor xi activation .
Evidently , the structural integrity of the prothrombin molecule is essential for its maximum binding to the antiserum , and antigenic sites are lost during its activation .
Assembly , activation , and signaling by kinin-forming proteins on human vascular smooth muscle cells .
Two of them were based on the prolongation of the activated partial thromboplastin time ( aptt ) using 2 different aptt reagents in the presence of apc , whereas the third method was based on the prolongation of prothrombin time when apc is added .
Postprandial activation of factors ix and vii occurred in the healthy individuals , whereas the plasma levels of xiia did not change in response to the test meal .
It was first recognized as a surface-activated coagulation system that is activated when blood or plasma interacts with artificial surfaces .
Purified hageman factor fragments ( prekallikrein activator ) induced an increase in factor vii activity in normal or hageman-trait plasma , but not in fletcher-trait plasma .
This activity was assumed to originate from a previously undescribed plasminogen proactivator whose activation is kallikrein - and factor xii-dependent .
Heat shock protein 90 ( hsp90 ) was identified as the protein responsible for zinc-dependent prekallikrein activation in the presence of hk .
Activation of the contact system was assessed by measuring plasma levels of factor xiia-c1-inhibitor and kallikrein-c1-inhibitor complexes as well as those of cleaved high molecular weight kininogen ( hk ) .
In normal human or fxii-deficient plasmas , but not in pk-deficient plasma , maximal activation was seen in 4 min .
We investigated whether differences in the plasmin - and thrombin activation system are associated with the predominate affection of females .
Thus , the appearance of factor xii-dependent coagulant activity correlates with the limited proteolysis of facto xii when normal or prekallikrein deficient plasma is activated by sulfatides or by kaolin .
The possible relation of this activation process to stimulation of synovial cells by cytokines is discussed .
Coagulation activators and inhibitors in the neointima of polyester vascular grafts .
125i-human high mr kininogen undergoes cleavage in plasma during contact activation initiated by addition of kaolin .
We show in this paper that the amount of surface required for activation is much reduced in the absence of c1 inhibitor ( hereditary angioedema ) or in the cold where the inhibitor loses much of its effectiveness .
The observations made provide support for the assumption that the low doses of estrogen used in hormone replacement therapy do not significantly affect the levels of contact activation or fibrinolytic factors in plasma .
Phbp digested alpha-chain and beta-chain of fibrinogen to prevent coagulation and cleaved single chain urokinase type plasminogen activator ( scupa ) to the active hetero dimer form ( tcupa ) .
Both plasmin and kallikrein amplify the inflammatory response by activating components of the contact activation system .
Although proteins of the kinin-forming pathway are bound along the surface of endothelial cells , the mechanism of activation of this proteolytic cascade is unclear .
Regardless of the triggers , pk can only be activated on hk bound to the artificial negatively charged or to cell membrane surfaces .
Cardiopulmonary bypass results in inappropriate activation of the coagulation and fibrinolytic systems .
Heparin is unable to prevent contact activation by three different membranes .
These numbers indicate that the activity detectable in native hageman factor is due to contamination with activated species .
The assembly and activation of the kinin forming system components on human umbilical vein endothelial cells ( huvec ) have been studied in great detail .
Our data support both factor xii-dependent ( rapid ) and factor xii-independent ( slow ) mechanisms ; the latter may require a cell-derived protein ( possibly protease ) to activate prekallikrein in the presence of zinc ion and hk .
Activation of the contact system in cerebrospinal fluid of patients with alzheimer disease .
No factor vii activation was observed during either regimen in factor ix-deficient patients , but a normal postprandial responsiveness of factor vii to dietary fat was restored in one patient who replicated the study after factor ix therapy .
An inhibitor of plasminogen activation behaved similarly in both groups .
The activation of the intrinsic pathway of blood coagulation and the production of bradykinin are among the sequelae of contact activation .
Two different plasmatic plasminogen activators ( pa ) can be demonstrated after sodium dodecyl sulfate polyacrylamide gel electrophoresis of plasma freshly collected from resting volunteers , followed by transfer of the gels onto plasminogen-rich fibrin-agarose plates .
Following surface-mediated activation of factor xi , further generation of factor xia was blocked by adding freeze-thawed platelets that contain cationic proteins which bind to negatively-charged surfaces ( j biochem 97 , 139-151 , 1985 ) .
Initiation of contact activation by sulfatides .
High and low molecular weight kininogens ( hk and lk ) are able to bind to platelets to inhibit thrombin binding to and activation of platelets .
This mystery has led several investigators to search for an "alternate" activation pathway for factor xi .
This action of aprotinin to inhibit contact-phase activation may influence the degree of anticoagulation with heparin .
Effect of a synthetic platelet activating factor on steroidogenesis of cultured porcine granulosa cells .
The same cleavage fragments were observed as obtained by activation of purified prekallikrein by beta-factor-xiia .
The data provide support for the hypothesis that the mechanism by which the 'surface' acts in contact activation involves the presence , on the same particle , of multiple binding sites for the proteins .
Binding of these proteins and contact system activation on an69-st membranes were reduced .
Both forms of amyloid precursor proteins inhibited ellagic acid-induced activation of hageman factor but did not inhibit activated hageman factor .
This may suggest that additional factors are involved in the postprandial fvii activation .
This study suggests that irreversible hypotension correlates with prolonged activation of the contact system , and specific antibody therapy can modulate both the pathophysiological and biochemical changes .
Only one patient with factor viii inhibitor presented with severe bleeding and was treated with recombinant human activated factor vii , while the others had no complications .
Cold-promoted activation of prorenin was within the normal range in plasma deficient in factor xi , x , ix , viiic , vii , v , prothrombin , or high mol wt kininogen .
Thus , factor vii was not activated in factor xii- , hmw kininogen- , xi- , and ix-deficient plasmas , but was activated in factor viii- , x- , and v-deficient plasmas .
Thus , mmp-10-induced activation of mmp-1 correlated with tube regression and gel contraction .
Plasma factor ix activation peptide and fibrinogen were positively associated with risk , but the relations were no longer statistically significant after adjustment for other factors , including viia and apoa-i .
Activation of the plasma clotting , fibrinolytic , and kinin-kallikrein system in preterm infants with severe idiopathic respiratory distress syndrome .
The results were compared to the influence of these membranes on the activation of purified fxii .
Both actions were suppressed by incubation with heparinase i. the maximum contact activation peak appeared at a lower mw than the anticoagulant effect .
Catalase gene expression was induced by 30 microm zinc in 6 h , but decreased to non-treated control levels by 24 h. the transcription factor sp1 was also activated by zinc treatment ( 30 microm ) which peaked at 2 h and declined to non-treated control levels by 24 h. catalase enzyme activity peaked at 24 h and decreased to control levels by 72 h. conclusions : .
These data indicate that during pregnancy both the contact phase and extrinsic pathway are activated .
Physiological concentration of hmwk had little or no influence on the activation of hf by sulfatides , kaolin , or glass , but higher concentrations ( 3 to 6 times more ) showed the same inhibitory effect as after activation by ellagic acid .
In contrast , one antibody ( baltimore ) or its fab' blocked the surface-mediated proteolytic activation of fxi by human fxiia in a concentration-dependent fashion by preventing its binding to hk , but had no effect on the rate of activation of fix by fxia .
The present study documents activation of the intrinsic coagulation pathway in a patient with severe pre-eclampsia .
Protein adsorption and complement activation were studied on thin evaporated films of titanium ( ti ) .
Separation of the vldl lipids indicated the phospholipid component as the major activating principle .
Thus , activation products of the contact system may be involved in the pathogenesis of angioedema and shock in insect-sting anaphylaxis .
Subsequently , the consequence of the inability of hmw-kininogen to associate with a negatively charged surface results in decreased surface activation .
Factor xii-dependent contact activation on endothelial cells and binding proteins gc1qr and cytokeratin 1 .
Initial experiments were required to find a procedure for characterizing the immobilization of fxii and its activated form , factor xiia ( fxiia ) .
Coagulation tests , such as activated partial thromboplastin time and activated clotting time , are used to monitor the effects of unfractionated heparin and the direct thrombin inhibitor , bivalirudin .
Thus , basic amino acid residues essential to the activation or activity of hageman factor appear to be variably accessible to chemical modification .
Activation of intrinsic coagulation pathway in pre-eclampsia .
Contact phase activation was investigated in_vitro using flat sheet type of haemodialysis membranes , cuprophan ( akzo , faser , germany ) and an69s ( hospal , france ) , and a negatively charged polyamide ultipor nr 14225 membrane as a control .
Though many bacterial species can directly activate individual coagulation factors , they have not been shown to directly initiate the coagulation cascade that precedes clot formation .
These zymogens must undergo an activation process , usually a limited proteolysis , to attain their catalytic activity .
In confirmation , extrinsic activator activity was recovered in plasma adsorbed by agarose-bound auk .
This defect was not associated with a bleeding diathesis , but should be considered as a cause of prolongation of the activated partial thromboplastin time .
Activation of the intrinsic or extrinsic coagulation pathway , or of both , causes formation of fibrin from fibrinogen by means of an elaborate and intricate system that also entraps platelets and activated coagulation proteins .
The increase in fviic is due to raised activated factor vii ( fviia ) activity , but is not associated with increased thrombin production or changes in fibrinolytic activity .
However , the heavy chain region of kallikrein is required for binding to high molecular weight kininogen , for surface-dependent activation of coagulation , and for optimal cleavage of high molecular weight kininogen .
The correlation between cytokine levels and coagulation activation may be related to the type of surgery performed .
Kinetic studies of the proteolytic activation of ( 125 ) i-labeled human hageman factor by human plasma kallikrein , plasma , activated factor xi , and trypsin were performed in the presence and absence of high molecular weight kininogen and surface materials such as celite , kaolin , or ellagic acid .
Thrombin can activate factor xi in the presence of dextran sulfate or sulfatides .
Activated coagulation times were maintained > 300 seconds by the hemochron method .
This impaired factor xi activation by rfxii-triangle up19a was also observed in a purified system and was independent of the presence of high molecular weight kininogen .
The serine protease had the activity to activate the kallikrein-kinin system in normal human plasma .
The potential action of forskolin may reside in a more stable complex of an activated stimulatory guanine nucleotide binding component and catalytic unit of the adenylate cyclase system .
The rate of activation of plasma prekallikrein was measured in samples taken from these patients before they received contrast agents .
The amino acid sequence of phbp is homologous to that of hepatocyte growth factor activator .
To the contrary , these collagen species inhibited activation of hageman factor by glass or ellagic acid .
Protein that inhibited contact activation and had antigenic properties of hmg-i and huvec lysate protein also was found in conditioned media from unchallenged cultured huvecs .
Hmw-kininogen was absolutely required for activation of pta by hf and ellagic acid .
We did not find a significant correlation between plasma heparin levels and concentrations of d-dimers , thrombin-antithrombin iii complexes ( tat ) , and prothrombin fragments f1+2 as markers of fibrinolysis and coagulation activation .
The protein concentration of that amount of supernatant fluid that inhibited activation by about half was 16 micrograms/ml , approximately the same as had been described for suspensions of peripheral blood mononuclear cells .
Prekallikrein activation on endothelial cells results in kinetically favorable single chain urokinase and plasminogen activation .
Activation of the system can be brought about by either increasing the catalytic rate ( in this study , by using more potent contact-activation conditions ) , or by lowering the enzyme inhibition rate .
From these results , the properties of porcine activated factor xi show great similarities with those of bovine and human activated factor xi .
Hereditary angioneurotic oedema and blood-coagulation : interaction between c1-esterase-inhibitor and the activation factors of the proteolytic enzyme systems .
This study was planned to assess in conscious normotensive rats whether the blood pressure response to the factor xiif is mediated by an activation of the plasma kallikrein-kinin system or by stimulation of prostaglandin synthesis .
Protein adsorption , contact activation , and complement activation were studied on thin evaporated films of chromium ( cr ) in_vitro .
These findings led us to conclude that hgf activator is present in plasma as an inactive zymogen and that the zymogen is activated by the cleavage of the bond between arg407 and ile408 by thrombin .
It is concluded from these experiments and modeling analysis that the primary mechanism for activation of coagulation involves autoactivation of fxii by the procoagulant surface or kallikrein-mediated reciprocal activation of fxii .
The rates of activation of the zymogens were separately measured by blocking either of the active enzymes with specific inhibitors , corn inhibitor for factor xiia ( ki = 67 nm ) and trasylol for plasma kallikrein ( ki = 39 nm ) .
The results suggest that activation of the contact system at the surface of s. aureus and the subsequent release of bradykinin could contribute to the hypovolemic hypotension seen in patients with severe s. aureus sepsis .
Activated partial thromboplastin time and minor coagulopathies .
When fxii was added with the pk , maximal activation occurred within 7.5-10 min .
Experimental results are modeled using a reaction scheme invoking fxii activation and autoinhibition linked to protein adsorption to procoagulant surfaces , where fxii activation is presumed to proceed by either autoactivation ( fxii-- > surface-- > fxiia ) and autohydrolysis ( fxii-- > fxiia-- > 2fxiia ) in buffer solution or autoactivation and reciprocal activation ( kallikrein-mediated hydrolysis ) in plasma .
However , the quantitative role of fxiia as a plasminogen activator in contact activation-dependent fibrinolysis in plasma is still unclear .
Streptokinase-induced activation of the kallikrein-kinin system and of the contact phase in patients with acute myocardial infarction .
Both during submaximal and maximal performance , tissue type plasminogen activator antigen , urokinase plasminogen activator antigen and tissue type plasminogen activator activity were increased .
The antibody ( p 5-2-1 ) consists of mouse igg2b heavy chains and lambda light chains , selectively neutralizes hf procoagulant activity , and prevents the proteolytic cleavage of hf during contact activation in plasma .
Activation of coagulation after administration of tumor necrosis factor to normal subjects .
A comparison of two aptt reagents which use silica activators .
The activated partial thromboplastin time was shorter than was that of human plasma , thus implying the presence of prothrombin in python plasma ; however , this protein could be demonstrated only in trace amounts .
Heparin and other oxygenator coatings have been used in attempts to reduce hemostatic activation during cardiopulmonary bypass ( cpb ) .
Therefore , one initiated , the process of intravascular activation of coagulation will perpetuate , this the more as platelets in turn will be stimulated into activity .
For the activation of platelets by cellulose the presence of plasma is necessary , rinsed platelets were not activated by cellulose .
Although factor ix activity was only slightly reduced ( mean 88% standard ) and factor ix antigen was normal , mean activated factor vii in patients was strikingly reduced to 34% of that in controls , a level similar to that found in haemophilia b. the patients' mean factor vii activity and factor vii antigen were also significantly reduced to 54% and 63% of those in controls , respectively .
Congenital deficiency or congenital dysfunction of inhibitors of activated clotting factors have provided insight into the functional principles of limited proteolysis .
Our findings indicate that the plasma contact system is activated in the ascites from cancer patients .
The effect of cs activation was investigated in the presence or absence of celite ( 10 mg ml ( -1 ) blood ) .
After prolonged treatment with tryptase , proenzymes could be fully activated with their specific activators .
Activation of the contact system in insect-sting anaphylaxis : association with the development of angioedema and shock .
These data indicate that em has inhibitory effects not only on the mrna expression and release of il-8 , but also on the activation of transcription factors nf-kappab and ap-1 .
A combined deficiency of factor viii and contact activation defect in a family of cats .
Tissue plasminogen activator inhibitor ( pai ) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy .
To test the sensitivity of the global assay of overall haemostasis potential ( ohp ) in detecting hypocoagulation , the ohp was assayed in plasma containing exogenous thrombin ( 004 iu/ml ) , tissue-plasminogen activator ( 330 ng/ml ) , ca and a platelet reagent .
Acute effect of smoking on fibrinolysis :increase in the activity level of circulating extrinsic ( tissue-type ) plasminogen activator .
Comparison of these sequences and the exon structures of the fibronectin and tissue plasminogen activator genes indicates that exons encoding type i and type ii repeats have reassorted during evolution .
More variable results were seen with collagen , but platelet activation in the presence of citrate was greater than that with cti .
The role of endotoxin immunity , neutrophil degranulation and contact activation in the pathogenesis of post-operative organ dysfunction .
Although congenital fxii deficiency is not associated with a clinical bleeding tendency , it can be identified on a routine coagulation test , such as a prolonged activated partial thromboplastin time .
A coagulation profile from a clinically normal female cat revealed an intrinsic coagulation defect characterized by prolonged activated partial thromboplastin time , with normal bleeding time , platelet count , and prothrombin time .
These domains may be involved in the conversion of the precursor to the active form of hgf activator .
Activation of the contact and complement systems in c1-inhibitor deficiencies is thought to contribute to the pathogenesis of angioedema attacks by releasing kinins .
(1) in a purified system , high molecular weight kininogen was absolutely required for activation of pta by hf and ellagic acid ( ea ) .
Recent studies indicate that assembly of high molecular weight kininogen on its multiprotein receptor allows for prekallikrein activation .
In the ascitic fluid of patients with cirrhosis , there is massive cleavage of high-m(r) kininogen and activation of fibrinolysis , but bradykinin has never been measured directly .
To investigate whether continuous venovenous haemofiltration using polyacrylonitrile filters causes activation of the contact system and intrinsic coagulation pathways and if this , and/or low plasma levels of endogenous anticoagulants , influences filter lifespan .
Furthermore , activation of prekallikrein by kaolin was observed in mouse plasma as amidase activity to produce fluorescence from the synthetic substrate .
Restenosis is a reparative process that is activated in response to injury induced by angioplasty .
Contact activation of plasma : structure-activity relationships of human high molecular weight kininogen .
Dextran sulfate activation of the proposita's plasma showed no proteolytic cleavage of f xii even after 120 minutes , whereas f xii in pooled normal plasma , diluted 1 : 10 with crm-negative f xii-deficient plasma , was completely cleaved after 40 minutes .
Thrombin generation and activation of fibrinolysis occurred with elevations in f1.2 , tat , and d-dimer .
Until recently it was believed that the main activator of factor xi is factor xiia in conjunction with the cofactor high molecular weight kininogen on a negatively charged surface .
Prekallikrein activation and high-molecular-weight kininogen consumption in hereditary angioedema .
Modification of arginyl residues of hageman factor by phenylglyoxal hydrate inhibits activation of this clotting factor in a plasma-free system , that is , in the absence of the other constituents of the contact activation system .
Experiments with inhibitors suggested that the spontaneous activation of c1s may consist of two phases :
Long-lasting depression of the factor xii-dependent fibrinolytic system in patients with myocardial infarction undergoing thrombolytic therapy with recombinant tissue-type plasminogen activator : a randomized placebo-controlled study .
Low doses of the platelet activating factor caused a slight decrease in progesterone production .
Beside contact activation , factor v activity also decreased in the plasma .
C-1-inactivator ( c-1-ina ) does not only exert its important inhibitory functions in the complement system but also in the first step in the activation of the coagulation , fibrinolytic and kallikrein system .
Studies on a complex mechanism for the activation of plasminogen by kaolin and by chloroform : the participation of hageman factor and additional cofactors .
Functional activity of antithrombin iii , alpha2-antiplasmin and protein c as well as quantitative determination of plasma concentrations of alpha1-antitrypsin , c1 activator inhibitor and alpha2-macroglobulin were also carried out .
Fibrinogen blocks the autoactivation and thrombin-mediated activation of factor xi on dextran sulfate .
The activated partial thromboplastin time ( aptt ) and prothrombin time were 20.1 +/- 1.6 and 9.7 +/- 0.3 s for rhesus and 32.0 +/- 5.6 and 12 +/- 0.5 s for human plasma .
Factor vii coagulant activity ( viic ) and xiia increased in both kinds of plasmas on incubation on ice for 24 h ( cold activation ) .
In addition , the mechanisms for amplification of activation of the proteins of the contact phase of coagulation will be discussed from the pivotal role of high molecular weight kininogen , or one of its altered forms , serving as a cofactor to order the activation of the zymogens it is associated with .
Sensitive and specific laboratory methods are now available to detect and diagnose states of coagulation activation , defined as a procoagulant imbalance between the production and inhibition of enzymes in the coagulation system short of fibrin deposition .
On the la heparin surface , a major portion of the surface-bound fxii was recovered in its enzymatically active form ( fxiia ) , but only trace amounts of the fxii taken up by the uf heparin surface had undergone activation .
We suggest that activated complement and/or contact system proteases may , at least in part , contribute to the attendant manifestations of septic shock through an augmentation of the cytokine response .
In_vivo demonstration in humans that large postprandial triglyceride-rich lipoproteins activate coagulation factor vii through the intrinsic coagulation pathway .
Perhaps because of reduced myocardial injury , inflammation , and activation of coagulation , patients undergoing the hybrid procedure had better perioperative outcomes and satisfaction , with excellent patency at 1 year's follow-up .
Activation of plasma coagulation by retransfusion of unwashed drainage blood after hip joint arthroplasty : a prospective study .
Washed platelets were not directly activated by oxidized cellulose within one hour .
Inhibition of prekallikrein activation by mab 13g11 was 55% ( rhesus plasma ) and 76% ( human plasma ) , with similar inhibition curves .
No increase in the o-2 generation rate of activated macrophages was observed upon the addition of paraquat to the culture medium .
To investigate potential mechanisms of thrombin formation in_vivo , to understand better the balance of coagulation and fibrinolysis during treatment with recombinant tissue-type plasminogen activator ( rt-pa ) , and to investigate the role of hemostatic markers as predictors of clinical events , we measured 3 markers of procoagulant activity :
These studies indicate that d3 of the kininogens contains both a binding region for platelets and endothelial cells and another region that inhibits thrombin-induced platelet activation .
The effect of the activating substances for transferring the hageman factor into its active form are represented with the role of the pre-kallikrein ( fletcher factor ) and of the highly molecular kininogen ( fitzgerald factor ) being referred to .
[comparative studies of measuring condition of activated partial thromboplastin time and contact factors in experimental animals]
Moreover , electrophoretic mobility shift assays revealed that nf-kappab activation occurred in the presence of silica , which was inhibited by antioxidants such as n-acetylcysteine ( nac ) .
The metalloprotease was confirmed to activate human factor xii-plasma kallikrein-kinin cascade that results in liberation of bradykinin , a chemical mediator enhancing the vascular permeability , from high-molecular weight kininogen .
Administration of gamma interferon in human subjects decreases plasminogen activation and fibrinolysis without influencing c1 inhibitor .
Cell-associated hk is proteolyzed during the course of prekallikrein activation , releasing kallikrein from the surface .
Furthermore , pre-incubation of hageman factor with tryptase did not diminish the subsequent activation of hageman factor by trypsin .
Addition of ot-2 , a monoclonal antibody inhibiting activated fxii , prevented the normalization of aptt .
After cardiac shock , in fhf and in infectious diseases coagulation and fibrinolysis may additionally be activated .
Nuclear factor-kappa b activation in silica-induced interleukin 8 production by human bronchial epithelial cells .
We found that the kallicrein-prekallicrein system was activated in our diabetic patients and that such activation could probably be secondary to lesions of the vascular endothelium present in long-term diabetics .
Intravascular coagulation and fibrinolysis in patients with ards also arise from components independent from contact system activation .
The pre-operative coagulation screen showed a prolonged activated partial thromboplastin time , 71.3 s ( normal range , 26-36 s ) , which was not corrected by the addition of normal plasma .
Activated factor vii ( viia ) was measured in 829 men .
The expression of cd61 did not alter during storage and the percentage of platelets expressing cd42b was > 88% in all units on day 7. rantes ( regulated on activation , normal , t-cell expressed and secreted ) and tgfbeta released from platelets by day 7 was < 800 ng/ml and 90 ng/ml , respectively .
The availability of engineered serine proteases allows one to study the activation , substrate specificity and regulation of human coagulation and fibrinolytic activities .
Estimation of how much of the variation in the levels of coagulation factors and measures of a prethrombotic state , including measures of protein c activation and inactivation , could be attributed to heritability and household effect .
In addition , these studies showed that normal plasma , but not plasma deficient in fxii , pk , or hk , activate upon binding to endothelial cells ( ec ) , and that this activation could be inhibited by antibody to gclqr .
Maximum enhancement of the prothrombin time resulted in shortening of the clotting time from 78.8 +/- 0.4 s to 68.5 +/- 0.6 s ( mean +/- sd , n = 8 ) in the presence of 50 micrograms/ml ( 15 mumol/l ) rgc1qr. rgc1qr also enhanced the intrinsic pathway of coagulation evaluated in the absence of activators of the contact system , as demonstrated by a shortening of the plasma recalcification time from 348 +/- 66 s to 140 +/- 23 s ( n = 4 ) .
The aptt was measured with plasma from the 2 horses after various incubation periods ( 1 to 15 minutes ) with a contact activator before the addition of ca ions .
Cold activation of complement i. presence of coagulation-related activator .
Thus both fragment 1.2 and the light chain region in hmw kininogen were essential for these activation reactions .
However , the fibrinogen deposited from normal plasma onto glass and similar wettable materials is rapidly modified during contact activation until it can no longer be identified antigenically .
The presence of a specific factor xiia inhibitor completely prevented the generation of plasmin amidolytic activity indicating that activation was mediated by proteolytical cleavage , although this could not be proven by western-blotting .
Therefore we feel that it will be helpful to conclude this article with a figure that summarizes those interactions and reactions that are generally believed to reflect the major molecular events occurring during surface-dependent contact activation .
Platelet factor 4 inhibited activation of hageman factor by ellagic acid , as measured by amidolysis of a synthetic substrate of activated hageman factor , an effect inhibited by heparin or by an anti-platelet factor 4 antiserum .
To assess the therapeutic efficacy of agents capable of stimulating the fibrinolytic system , such as tissue plasminogen activator ( t-pa ) and urokinase ( uk ) on endotoxin-induced disseminated intravascular coagulation ( dic ) in the rabbit .
Endotoxin-induced hypotension in rats is not mediated by prekallikrein activation .
The amino-terminal sequences of the chains of activated factor vii were found to be ala-asx-gly - and ile-val-gly- , the same as were earlier observed after activation of factor vii by activated factor x. this finding indicates that initiation of coagulation by the intrinsic pathway also primes the extrinsic pathway .
However , the demonstration that the contact system may be activated in the brains of alzheimer patients points to the potential involvement of the kallikrein-kinin system in the inflammatory process of this disease .
After activation of hageman factor with solutions of ellagic acid , a negative trough appeared in the region of the circular dichroism spectrum commonly assigned to tyrosine residues , along with other minor changes in the peptide spectral region .
The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia .in_vivo use of a monoclonal anti-factor xii antibody to block contact activation in baboons .
On the other hand , beta2gpi inhibits anticoagulant activity of activated protein c. according to the data from knockout mice , beta2gpi may contribute to thrombin generation in_vivo .
These studies indicate the pivotal roles of the contact phase of coagulation in initiating activation of the pt and of ci inh in inhibiting the activation of the coagulation factors responsible for the cold-promoted activation of factor vii .
These results are consistent with the hypothesis that hmrk and hageman factor form a complex on kaolin which renders hageman factor more susceptible to proteolytic activation by kallikrein and which facilitates the action of activated hageman factor on its substrate proteins , factor xi and prekallikrein .
Mmp-1 activation by serine proteases and mmp-10 induces human capillary tubular network collapse and regression in 3d collagen matrices .
Our results demonstrate that zinc treatment of rpe cells increases catalase expression and activates the transcription factor sp1 .
Preadsorption of igg , fibrinogen or fibronectin decreased the quantitative expression of il-1 beta but increased the functional activity in the thymocyte proliferation assay indicating the presence of monocyte/macrophage activation products which either downregulated the activity of il-1 beta or upregulated thymocyte proliferation in an independent fashion .
Xiia was assayed as prekallikrein ( pk ) activator .
Initiation of contact activation may also involve the expression of low intrinsic catalytic activity of these zymogens .
The response to contact with pvc appears to begin with a low-grade generation of thrombin that involves both erythrocytes and leukocytes and that activates platelets , followed by the activation of a platelet-dependent amplification loop that produces most of the thrombin .
Protein adsorption and macrophage activation on polydimethylsiloxane and silicone rubber .
Moreover , it was found that surface-binding of human and bovine hageman factor renders these molecules 100 to 1000 times more susceptible to proteolytic activation by kallikrein , plasmin , or other proteases .
Here , we report a salivary protein of the malarial vector mosquito , anopheles stephensi , that inhibits activation of the plasma contact system .
The influence of the inhibitors c1 esterase-inhibitor , alpha 2-macroglobulin , antithrombin iii , and alpha 1-antitrypsin on the activation of prorenin was studied in factor xii-deficient plasma from which one or more of these inhibitors had been selectively removed by immunoadsorption .
Prolongation of the aptt and loss of contact factor activities was not observed in plasma incubated with particulate activator reagents .
Dextran sulphate activated contact factor mediated fibrinolysis was decreased in group 2 ( median 952% ) compared with group 1 ( 1210% ) and controls ( 1317% ) .
Thereafter , platelet bound factor xi can be proteolytically activated to factor xia either in the presence of factor xiia or in the presence of kallikrein .
The degree of liver disease was graded according to the child-pugh classification , the intensity of s. mansoni infection was monitored by determination of circulating schistosome immune complexes ( csic ) level using a monoclonal antibody and hemostasis activation was detected by measurement of hemostatic markers d-dimer and prothrombin fragment 1 + 2 ( f1+2 ) .
Incubation of c1q with hf before addition of hf-deficient plasma extended the activated partial thromboplastin time .
Conclusions : prolongation of activated partial thromboplastin time in streptococcal toxic shock syndrome is associated with activation of the contact system , possibly contributing to the profound shock associated with streptococcal toxic shock syndrome .
In contrast , modification of amino groups in n-terminal and lysine residues inhibits activated hageman factor .
This confirms that contact activation is not specific to anionic hydrophilic surfaces as proposed by the accepted biochemistry of surface activation .
The activation of complement in the cold could be prevented by increasing the ionic strength , or by adding vitamin e or , to a lesser extent its vehicle hco-60 , while heparin , trasylol , soybean trypsin inhibitor , or hirudin had no effect .
The catalytic efficiency ( kcat/km ) for factor x activation by factor viiia/factor ixa is far in excess of the catalytic efficiency of activation of factor x by tissue factor/factor viia ( table 3 ) .
Heparin derived from human mast cells therefore seems to represent the physiological macromolecule capable of activating the contact system and could be a missing link between cellular and humoral responses in allergic reactions .
Thrombin formation was evaluated in platelet-poor plasma activated in the presence of heparin ( 0-5 u/ml ) or bivalirudin ( 0-30 microg/ml ) using a thrombin generation assay ( thrombinoscope ) .
Activated gel-filtered platelets promoted factor xi activation by thrombin at initial rates 2-5-fold greater than dextran sulfate in the presence of high molecular weight kininogen ( hk , 45 nm ) , zncl2 ( 25 microm ) , and cacl2 ( 2 mm ) , conditions optimal for factor xi binding to platelets .
The bromelain-treated mouse plasma released kinin amount of less than detection limit when activated with kaolin , whereas normal plasma released about 300 ng/ml of kinin of bradykinin equivalent as assessed by rat uterus contraction .
Patients treated with aprotinin showed higher concentrations of single-chain urinary type plasminogen activator ( scupa ) at the end of cpb compared with control patients , indicating reduced contact - phase [correction of contact phase] activation .
Coagulation system and platelets are fully activated in uncomplicated sepsis .
In_vitro activation of complement and contact system by lactic acidosis .
Human high molecular weight kininogen .studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma .
To investigate whether vegf is released from platelets during coagulation activation in_vivo , we measured in human subjects vegf at the site of plug formation , ie , in blood emerging from a standardized injury made to determine bleeding time ( shed blood ) .
The mechanisms involved in the activation of the coagulation cascade in severe falciparum malaria were studied in 22 adult patients ( 19 male , three female ) aged 18-45 ( mean +/- sd 31 +/- 11 ) years .
This inhibitory property of hmwk may be attributed to competitive binding of hf and hmwk on the surface of the activating agents .
Protein c and protein s were present in all observation periods , as well as prothrombin activation fragment f1 + 2. results indicate a high thrombotic potential of the graft neointima early after prosthesis implantation , whereas in the late postoperative follow-up increasing expression of coagulation inhibitors reduces thrombotic properties of the graft neointima .
The plasminogen activating activity in normal plasma was only partially blocked ( for 77% ) with specific antibodies to tissue-type plasminogen activator ( t-pa ) and urokinase-type plasminogen activator ( u-pa ) .
A sensitive assay for quantitating bovine activated factor xi ( factor xia ) in_vitro was developed by measuring the amidolytic activity of thrombin generated in a mixture of factors xia , ix and x and prothrombin prepared from bovine source and washed bovine platelets .
In the collective with a low blood loss , we found remarkable cell alterations as well as highly activated and advanced coagulation and an extraordinary fibrinolytic activity .
The high-fat test was associated with an increase in plasma triglyceride and kallikrein concentrations and postprandial fvii activation ( p < 0001 ) .
Prekallikrein activation is dependent on the presence of high molecular weight kininogen and an optimal free zn2+ concentration .
Surface-bound factor xiia is then responsible for the activation of factor xi to factor xia , thereby propagating the initial trigger .
Characterization of bovine factor xiia ( activated hageman factor ) .
In this report we investigated the effect of fibrinogen , the major coagulation protein in plasma , on the activation rate of factor xi .
Kinetic analysis of pro-uk activation by kallikrein showed promotion of the reaction by platelets .
Factor ix is a vitamin k-dependent glycoprotein that can be activated by factor xia or the factor vii-tissue factor complex in_vitro .
In contrast , once hageman factor was activated by kaolin , its clot-promoting properties were not inhibited by beta 2-glycoprotein i. further , beta 2-glycoprotein inhibited the generation of amidolytic activity against h-d-prolyl-l-phenylalanyl-l-arginine p-nitroanilide dihydrochloride in mixtures of hageman factor and ellagic acid .
Markers of thrombin generation and platelet activation are often elevated in patients with nonvalvular atrial fibrillation , but it is unclear whether such markers usefully predict stroke .
Understanding the importance and physiologic activity of the plasma kallikrein/kinin system ( kks ) has been thwarted by the absence of an inclusive theory for its assembly and activation .
These tests were selected for their relationship to the contact coagulative activation near the vascular wall .
Activation of plasminogen by factor xiia followed the michaelis-menten rate equation .
It also revealed a general robustness of the system to changes in procoagulant concentrations , inhibition rates and most activation rate constants .
A first step in further research might be in understanding the increase in coagulation activation ( f 1 + 2 ) which has so far not been satisfactorily related to changes in blood concentrations of haemostatic factors and possibly local factors .
Activation of the contact system of plasma proteolysis in the adult respiratory distress syndrome .
Thus , smoking appears to elicit a significant increase in the level of activity of circulating extrinsic plasminogen activator .
When monitoring factor xiia activation of plasminogen in a clot lysis assay , the clot lysis time was 2 - to 4-fold as long as that accommodated by urokinase at factor xiia concentrations equivalent with 5-20% of the zymogen concentration in plasma .
Heparin , derived from the mast cells of human lungs is responsible for the generation of kinins in allergic reactions due to the activation of the contact system .
On the contrary , these aggregates showed a potent inhibitory activity on the activation of those zymogens triggered by kaolin , amylose sulfate and sulfatide .
Nineteen lots of 25% albumin were tested and found to be free of detectable amounts of prekallikrein activator .
Our model indicates that the tissue factor-factor viia complex initiates coagulation by activating small amounts of both factor ix and factor x in the environment of the tissue factor bearing cell .
Activation of prorenin in the neutral phase after ph 3.3 dialysis of human plasma depends on clotting factor xii-initiated prekallikrein to kallikrein conversion .
The reaction was activated by kaolin in the euglobulin fraction .
Because activation of platelets and of the coagulation system are interdependent mediators of thrombosis , platelet activation was characterized in whole blood in the presence of anticoagulants used to assess platelet function in_vitro or as treatment for patients with occlusive arterial disease .
Complexity of coronary stenosis was positively correlated with tissue-type plasminogen activator ( tpa ) mass concentration ( p < 001 ) and pai activity ( p < 005 ) .
Baseline levels of c4a and plasmin-alpha 2 antiplasmin complexes increased , and , on activation with kaolin , levels increased further .
Similar findings were observed for mice deficient in factor xi , a substrate of activated fxii .
Our results demonstrate , that angiography causes a significant activation of the kallikrein-kinin as well as of the complement system in spite of the use of newer non-ionic contrast agents .
They were more regular and intensive after the activation of this factor .
The factor xii-dependent fibrinolytic activator activity and the extrinsic ( tissue-type ) plasminogen activator were significantly higher ; however , the urokinase-like fibrinolytic activator activity was significantly lower .
Kininogens , themselves , are selective inhibitors of alpha-thrombin-induced platelet activation preventing alpha-thrombin from cleaving the cloned thrombin receptor after arginine41 .
The study suggests a relationship between activation of blood coagulation factors and the type of asthmatic response elicited after challenge test .
We found systemic activation of clotting , fibrinolysis , and kinin-kallikrein in the irds infants within 12 to 24 h of birth , represented by increased median thrombin-antithrombin iii complex formation ( 90 ng/ml versus 10 ng/ml in the reference group , p < 005 ) , increased mean tissue-type plasminogen activator plasma concentrations ( 118 ng/ml versus 35 ng/ml in the reference group , p < 005 ) , and increased mean plasma kallikrein activity ( 1826% versus 1620% of maximal activated human plasma in the reference group , p < 005 ) , respectively .
A general pattern of activated blood coagulation and endothelial activation is present in all hyperlipidemic subjects studied , independent of metabolic phenotype .
Partial hepatectomy and administration of carbon tetrachloride or galactosamine caused the conversion of pro-phbp to the active form in mouse but administrations of turpentine and mercury chloride did not , suggesting the hepatic injury specific activation of phbp .
An activation of the hemostasis and a disturbed fibrinolysis are known .
For more than three decades , it has been known that the plasma kallikrein/kinin system becomes activated when exposed to artificial , negatively charged surfaces .
Fibrinolytic activity was determined by assaying tissue plasminogen activator ( tpa ) and plasminogen activation inhibitor type 1 ( pai-1 ) .
Mast cell derived heparin activates the contact system : a link to kinin generation in allergic reactions .
Our findings indicate that triglyceride-rich lipoproteins activate prokallikrein postprandially , which might form an important initial event in fvii activation after consumption of high-fat meals .
In the pulmonary vein plasma levels of activated factor vii decreased following heparin administration ( p < 0001 ) in the majority of patients which was coincidental to an increase ( p < 0001 ) in tissue factor pathway inhibitor ( tfpi ) .
Activation of plasminogen-free rat citrated plasma ( rcpl-p ) with acetone/kaolin yielded baee-esterase activities of 0.6--0.8 u/ml .
Recent experiments have demonstrated that tf-dependent activation of the coagulation cascade plays an important role in the pathophysiology of intravascular thrombus formation .
As the reaction proceeded , considerable anticoagulant activities emerged , but the bradykinin and the plasminogen activator levels even further increased .
How fxii is activated in_vivo remains poorly understood as the concentration and density of surface bound negative charges known to trigger the activation in_vitro is far from sufficient in_vivo .
Because the activated partial thromboplastin clotting times in prekallikrein deficient plasma approach normal values upon prolonged incubation with kaolin , this phenomenon was studied and found to be even more pronounced in the presence of sulfatides .
These studies indicate that matrix of various ec has the ability to assemble hk allowing for pk activation and subsequent activities .
Collagen increased the clot-promoting activity of partially purified hageman factor but exerted no further effect in the presence of kaolin , a known activator of hageman factor ; clot-promoting eluates were obtained from collagen exposed to normal , hemophilic , or ptc-deficient plasma but not from collagen exposed to hageman or pta-deficient plasma .
The determination of plasma prekallikrein by direct activation with beta-xiia in the presence of acetone offers several advantages over the use of contact activators such as dextran sulfate .
Among these enzymes , only bromelain and trypsin showed clear activating effects .
Our data indicate that the studied lmwh preparations have a major impact on blood clotting in the activated state and inhibit in_vivo the hemostatic system to a comparable extent .
By incubation of human citrated plasma with acetone 25% v/v kallikrein inhibitors were destroyed and prekallikrein activated to kallikrein .
We conclude that sms completely prevented hg/hi-induced tf activation in normal volunteers and may be of use to reduce the procoagulant state and acute vascular events in hyperinsulinemic insulin-resistant patients with type 2 diabetes .
These studies indicate that the unstimulated external platelet membrane has a binding site for hmwk that could serve as a surface to modulate contact phase activation .
These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of beta2gpi .
These data indicate that the potential value of activations peptide assays such as f1.2 in this setting should be tested in prospective clinical trials .
In a murine model of streptococcal necrotizing fasciitis , the activated partial thromboplastin times were significantly prolonged in infected mice compared with controls , whereas prothrombin times were normal , suggesting an isolated abnormality of the intrinsic pathway .
In this study , we investigated the frequency of resistance to apc in patients with advanced cancer and examined the relationship of apc resistance to other markers of coagulation activation .
Plasma kinin activation in tranexamic acid treated patients with hereditary angioneurotic edema .
Considered together the observations on contact factors made in this study provide support for the assumption of an increased readiness for contact activation in plasma from women using oc .
Tec cell separator has very little , if any , effect on the activation of fibrinolysis .
No activation of the adsorbed fxii was detected .
In the presence of dextran sulfate , thrombin or factor xa activated factor xi .
To test whether endotoxin decreases blood pressure acutely in rats by activating the plasma kinin-forming system , plasma kallikrein activity was determined in different experimental settings of endotoxemia .
The multiple coagulant activities of bell and alton phospholipids ( ie pf3 , tissue factor and contact activating ) may account for the absence of coagulant superiority of platelets in the undiluted system in plastic tubes .
Increased fibrin specificity and reduced paradoxical thrombin activation of the combined thrombolytic regimen with reteplase and abciximab versus standard reteplase thrombolysis .
Fxii activation after pk activation contributed to the extent of measured enzymatic activity , but its role was secondary because treatment with corn trypsin inhibitor or a neutralizing antibody to fxiia did not abolish the measured enzymatic activity .
The bound pkrn-hk complex prevents the release of generated fxiia and therefore further binding and activation of fxii from the bulk phase .
The ultrafiltrate is regenerated by passage through a sorbent cartridge made up of resin and activated carbon .
Practical approach to anticoagulation for cardiopulmonary bypass in the patient with congenital prolonged activated partial thromboplastin time .
Plasma plasminogen activator inhibitor-1 ( pai ) antigen , fibrinogen , antithrombin iii ( atiii ) , protein c , beta-thromboglobulin ( btg ) , platelet count , fibrinogen degradation product ( fdp ) d-dimer , factors vii and xii , as well as cholesterol , triglyceride ( tg ) and glucose were determined in 163 subjects .
Activation of pk on huvec required an optimal substrate and zn2+ concentration , the latter of which varied with the buffer's carrier protein .
Erythromycin suppresses nuclear factor-kappab and activator protein-1 activation in human bronchial epithelial cells .
In previous work benzamidine was found to protect the cofactor function of purified hmrk in the assay system used , and edta was found to inhibit purified human plasma kallikrein assayed as plasminogen activator .
Thus , prevention of contact system activation , beside diminishing the recruitment of glial cells and microvascular permeability , can also decrease the activation of complement system and the release of il6 , both factors being considered to play an important role in the inflammatory reactions in ad brain .
Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit .
The activated contact factor was assayed as prekallikrein activator ( pka ) , as s-2222 amidase , and in radial immunodiffusion tests .
In the more severe forms of liver disease the time necessary to activate prekallikrein is increased .
When prekallikrein ( pk ) assembles on high molecular weight kininogen on huvec , pk is activated to kallikrein .
Plasma plasminogen , antithrombin 3 , and prekallikrein decreased significantly while plasma plasminogen activator inhibitor increased significantly .
In this review , special interest is given to the new role of factor xi in coagulation , with emphasise on data supporting the concept of thrombin-mediated factor xi activation in_vivo .
In addition , activated lymphocytes have been reported to release soluble gc1qr .
At day 7 all three coagulation activation markers were significantly higher in patients with subsequent adverse clinical outcome .
It was found that a range of approximately 40-55% of the nucleotide bases were placed at identical positions in the kringles , with the highest number found in the alignment of the two kringles of human tissue plasminogen activator and the lowest number in the alignment of the s kringle of prothrombin with the second kringle of tissue plasminogen activator .
The integrated structure of calmodulin consisting of n-terminal half domain , c-terminal half domain , and the linker peptide was indispensable for the enzyme activation .
Assembly of high molecular weight kininogen and activation of prekallikrein on cell matrix .
Porcine factor xi and activated factor xi were purified by the introduction of affinity chromatography on high molecular mass kininogen .
The activation of the latter is deeply involved in inflammation and pain sensation .
The magnitude of the activation of fibrinolysis partly depends on the mw of the substance but apparently also on the degree of sulfation since a low mw substance with a high number of sulfate bonds such as sp 54 was considerably more active than the low mw fraction of standard heparin .
We conclude that plasma fxiia is under strong genetic control but also reflects plasma triglycerides and endothelial activation or dysfunction .
30,000 ) activated pta in the absence of hmw-kininogen and ellagic acid .
Following the activation of tf pathway in plasmas depleted of factor x or factor ix , the inhibitory effect of fondaparinux on fviia generation was completely abolished , whereas it was not significantly modified when the other clotting factor-depleted plasmas were clotted .
These data also indicate that no significant contact activation , as measured by pcfia , occurs during leukodepletion of platelet concentrates with either filter a or b .
Endothelial cells produce a substance that inhibits contact activation of coagulation by blocking the activation of hageman factor .
Inhibition rather than enhancement of hemostatic system activation during initiation of oral anticoagulant treatment .
Determination of thrombin antithrombin complexes is considered to establish the most sensitive short-term reacting parameter indicating activation of coagulation .
This culture system should prove useful for identifying species differences in the signal transduction mechanisms underlying the activation of mel secretion in the mammalian pineal .
Intraoperative administration of at iii concentrates allowed adequate anticoagulation during cpb and attenuated the coagulative cascade activation and the consequent consumptive coagulopathy .
Bacterial collagenase-induced haemorrhage presumably resulted from enzymatic destruction of membranous structures ; at least a portion of the inflammatory response may be due to activation of a kinin-like system .
There is both a baseline rise in blood pressure and systemic platelet activation as well as superimposed labile rises of both .
The pglcnac polymeric fiber provides hemostasis through redundant mechanisms that include platelet activation for fibrin network formation .
Contact activation : a revision .
The adhered platelets were rounded or mildly pseudopodic and did not express p-selectin , an activation marker .
It can in_vitro activate the coagulation factor fvii , kininogen and plasminogen activators .
These results obtained in unanesthetized rats strongly suggest that the blood pressure fall induced by e. coli endotoxin is not due to activation of prekallikrein and consequently of the kinin-forming system .
It is concluded that in_vitro the increased amount of contact surface in the late pregnancy plasma promotes a higher rate of generation of xiia and consequently a higher rate of activation of factor vii .
The crystal structure of the catalytic domain of human urokinase-type plasminogen activator .
These data suggest that trace proteins , such as those important in the activation of the coagulation cascade , can significantly affect the blood compatibility or thrombogenicity of an implanted device .
In both groups , active plasminogen activator inhibitor type 1 ( pai-1 ) first decreased during cpb and then increased above baseline postoperatively .
Activation and consumption of hageman factor in the anaphylactic shock of the rat .
It also binds factor xi and inhibits its activation .
Acetone activation of rcpl-p and of rcpl yielded prekallikrein activator ( pka ) activities which were about doubled by treatment with kaolin to 1.9--2.1 and 3.5--4.2 pka-u/ml respectively .
These experiments , then , support the view that the procoagulant function of hmwk is localized to a point subsequent to the activation of hf .
Factor xi adsorption from plasma to activating surfaces was tested by adding a small amount of 125i-labeled purified factor xi to plasma , exposing the mixture to a glass tube or kaolin , and determining the amount of factor xi adsorbed to the surface .
Effects of high concentrations of energy sources and metabolites on suspension culture of chinese hamster ovary cells producing tissue plasminogen activator .
Contact activation was observed as an immediate , transient and surface-dependent phenomenon .
These assay methods have dramatically improved our understanding of the mechanistic role of coagulation activation in health and disease .
Our data demonstrate that platelet activation , factor xii-driven thrombus formation , and plasmatic coagulation pathways downstream of fx are not a prerequisite for ensuing tissue damage in models of photothrombotic vessel injury indicating that other pathomechanisms are involved .
Beta2gpi is involved in coagulation and fibrinolytic systems , including inhibition of contact activation .
Inhibition of prekallikrein activation in human plasma by components of bovine plasma .
The aim of this placebo-controlled study was to find out whether an extended pretreatment period with clopidogrel before an elective pci might confer a superior inhibition of the platelet activation and aggregation than clopidogrel given not until pci .
We conclude that fibrin-bound thrombin is capable of factor xi activation .
Further , hyperfibrinogenemia and persistent platelet activation exist in patients with vads , likely contributing to speed of clot growth .
Findings of prolonged activated partial thromboplastin time ( aptt ) and lupus anticoagulant are rare in asymptomatic children and are often preceded by certain types of surgery .
In contrast to other thrombolytics , tenecteplase ( tnk-tpa ) does not show paradoxical thrombin activation , indicating a lower procoagulant effect of this fibrin-selective thrombolytic agent .
Once activated , plasma kallikrein is rapidly inactivated by the naturally occurring plasma inhibitor , but the inhibition is incomplete .
38.1 +/- 29.4 versus 10.5 +/- 4.2 microg/l ; p < 0.01 ) , indicating paradoxical thrombin activation .
Our major findings show an anti-invasive role of il-12 , associated with an inhibitory effect on the proteases but with an opposite up-regulating influence on the protease inhibitor , timp-1 , whereas timp-2 and plasminogen activator inhibitor 1 remained unaltered .
Testing for passovoy defect in children with prolonged activated partial thromboplastin time ( aptt )
However , all these solutions , except of ringer solution , activated hageman factor and prekallikrein in human blood serum .
Demonstration and mode of action of an inhibitor for activated hageman factor ( factor xiia ) of the intrinsic blood coagulation pathway from schistosoma mansoni .
Kinetic analysis of the reaction demonstrated that the kcat/km was 1.2 x 10(5) m-1 s-1 in the absence and 1.1 x 10(6) m-1 s-1 in the presence of zn2+. zn2+ were also required for inositol-phospholipid-accelerated initiation of the contact activation in whole plasma .
The k(m) of pk activation by prcp is 6.7 nm .
Clinical investigation of these phenomena is warranted in clinical settings involving contact activation ( eg , intra-aortic balloon pumps and ventricular assist devices ) to determine whether these devices modulate fibrinolysis and perhaps contribute to thromboembolic morbidity .
Novel roles for factor xii-driven plasma contact activation system .
This supports the hypothesis that binding to endothelial cells protects the activated fxii against inactivation by its major endogenous inhibitor .
Similarly , proteins of the plasma kinin-forming cascade can be activated by binding to aggregated a ( beta ) protein of alzheimer's disease .
An extensive study of coagulation profile compared different assays to investigate lupus-like inhibitor : the most sensitive assay was the partial thromboplastin time performed without activator .
While ca ( ii ) did not replace zn ( ii ) as an activator it significantly enhanced zn ( ii ) - and p(i) -dependent activation of fxii .
Immunoaffinity columns prepared from each antibody were able to bind the heavy but not the light chain of reduced and alkylated activated fxi ( fxia ) .
Recently , it has been shown that factor xi can be activated by thrombin , resulting in the generation of additional thrombin via the intrinsic pathway .
Hageman factor previously activated by ellagic acid ( factor xiia ) retained full enzymatic activity in the presence of microfilarial extract ( 01 mg/ml ) .
Among the many entities that comprise the kks , high molecular weight kininogen ( hk ) , a bradykinin precursor , is critical in the assembly and activation of this system .
However , in plasma this activation has been shown to occur only with exogenous fxi and a non-physiological cofactor ( sulphatides ) , and the occurrence of this reaction in a plasma environment has been questioned .
The ortho activated partial thromboplastin time ( aptt ) reagent , thrombosil 1 ( ts ) , was compared to the general diagnostics automated aptt reagent ( gd ) .
The initial vascular response to injury produces brief vasoconstriction and exposes subendothelial substances that attract circulating platelets and activate coagulation proteins .
Exposure of serum containing added uroporphyrin , coproporphyrin , and protoporphyrin , but not hematin , to ultraviolet light ( 405 nm ) resulted in activation of the classical pathway of the complement system .
Comparisons of sti-sensitive and sti-resistant arginine esterase activities of plasma samples from cystic fibrosis patients , obligate heterozyotes or other groups showed no significant differences in levels of activity , kinetics of activation or gel chromatographic behaviour .
In a randomized placebo-controlled study , seven patients with acute myocardial infarction allocated to intravenous treatment with 100 mg of recombinant tissue-type plasminogen activator ( rt-pa ) and seven patients allocated to placebo were studied during eight sampling periods before and after treatment .
Activation of bovine factor vii by hageman factor fragments .
C1 inh inactivation of c1r and c1s within activated macromolecular c1 results in dissociation of c1 with release of complexes consisting of two molecules of c1 inh and one molecule each of c1r and c1s .
We assessed global coagulation tests ( prothrombin time , activated partial thromboplastin time ) , fibrinogen , prothrombin fragment f 1 + 2 and a variety of factors ( factors ii , v , vii , xiii , ix , x , xi , xii , xiia ; von willebrand factor ; collagen-binding activity , prekallikrein , high-molecular weight kininogen ) and antagonists ( antithrombin iii , protein s activity , free protein s ) .
Plasma fxii activity was markedly decreased in the onset and florid stages of nephrotic syndrome , and this decrease was not correlated with plasma albumin level , which suggested marked activation of this factor in these stages .
These results suggest that large lipoprotein particles carrying the appropriate free fatty acid at a sufficient density of negative charge could provide the contact surface that induces the generation of factor xiia and the subsequent activation of factor vii .
This activation is dependent on the presence of high molecular weight kininogen and an optimal zinc ( zn2+ ) concentration .
These include coagulation , fibrinolysis and complement activation .
A fall in tissue plasminogen activator activity and a rise in plasminogen activator inhibitor activity highly correlated with a lethal outcome .
In a prospective study assessing haemostatic functions , the activated partial thromboplastin time was prolonged in 134 out of 10,229 patients studied , without an increase in the prothrombin or thrombin times ; this abnormality persisted in only 37 of them on a new blood sample .
A deficiency of a factor of the contact activation system ( fxii , prekallikrein , high molecular weight kininogen ) is usually diagnosed during routine coagulation tests demonstrating a prolonged aptt .
Together with previous observations that kallikrein generated chemotactic activity , possibly via activation of c5 , the present observations suggest that prekallikrein activation may be important for in_vivo leukocyte chemotactic response to skin abrasion .
The activation of prekallikrein by factor xiia , ( reaction 2 ) proceeded even in the absence of high-mr kininogen and kaolin .
Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock .
Activation of the tissue factor pathway of blood coagulation in patients with chronic urticaria .
Preincubation of factor xi with activated platelets and thrombin or factor xa enhanced subsequent thrombin generation in the model system .
These data demonstrate that aggregated abeta can bind and activate proenzymes of the plasma kinin-forming cascade in a zinc-dependent reaction to release bradykinin and is of sufficient potency to do so at physiologic concentrations of each protein and in the presence of naturally occurring protease inhibitors .
Thus , in patients with ami receiving thrombolytic therapy , early activation of inflammation parallels the activation of the contact system and the coagulation cascade , which might contribute to microvascular obstruction and reperfusion injury .
The plasma of crocodilians and testudines ( turtles and tortoises ) contains all the components of the kallikrein-kinin system found in mammals ( prekallikrein activator , prekallikrein , kininogen , and kininases ) and activation results in generation of [thr6] -bk .
The addition of trypsin , the neutrophil serine proteases ( neutrophil elastase and cathepsin g ) and the mast cell serine proteases ( tryptase and chymase ) each caused mmp-1 activation and collagen type i proteolysis , capillary tubular network collapse , regression and ec apoptosis .
The results fail to provide convincing evidence ofr activation of the plasma kinin system leading to free bradykinin or a significant role for bradykinin in the immunopathogenesis of dhf .
Increased levels of tissue-type plasminogen activator and of urokinase-type plasminogen activator/receptor are measurable in atheromas .
Rather , contact activation in the presence of proteins unrelated to the plasma coagulation cascade leads to an apparent specificity for hydrophilic surfaces that is actually due to a relative diminution of activation at hydrophobic surfaces and an enhancement at hydrophilic surfaces .
Putative fxiia produced by surface activation with both hydrophilic and hydrophobic procoagulants was shown to hydrolyze blood factor xi ( fxi ) to the activated form fxia ( fxifxiia-- > fxia ) that causes fxi-deficient plasma to rapidly coagulate .
To determine if rhesus monkeys ( macaca mulatta ) could serve as a model for studying the role of the contact system in the pathophysiology of human infections , we compared structural , kinetic , and functional characteristics of plasma prekallikrein and its activation products in rhesus and humans .
Activity related to tissue plasminogen activator ( t-pa ) or urokinase ( u-pa ) was quantified by antiserum inhibition .
[study of the mechanism of adsorption and activation of enzymes of the contact phase of blood coagulation]
Evidence for a prekallikrein activator in fish plasma is lacking but treatment with exogenous proteases generates [arg0 , trp5 , leu8] -bk ( trout and cod ) , [trp5] -bk ( bowfin and gar ) , [met1 , met5] -bk ( sturgeon ) .
Both of these findings argue against the standard view that contact activation of plasma coagulation is potentiated by the assembly of activation-complex proteins ( fxii , fxi , prekallikrein , and high-molecular weight kininogen ) directly onto activating surfaces ( procoagulants ) through specific protein/surface interactions .
Our data do not support the view that factor xii-plasma kallikrein or plasmin dependent pathways are involved in the activation of inactive renin in_vivo .
On a molar basis , trypsin was twice as potent as kallikrein in the cleavage of the surface-bound hageman factor , while plasmin and activated factor xi were an order of magnitude less potent than kallikrein .
Despite advances in research , the underlying mechanisms that activate vsmc toward vascular disease are poorly understood .
D3 , like hk and lk , inhibited thrombin-induced platelet activation by preventing thrombin binding to platelets .
Furthermore , activation of pre-kallikrein was delayed in these patients .
Selective inhibitors of kallikrein not only block its activation but play a predominant role in inhibiting elastase release .
The assay for activated coagulation factors has recently been considered to be a useful tool for detecting hypercoagulable state .
Effect of surfaces on fluid-phase prekallikrein activation .
Addition of bovine plasma to human plasma caused significant inhibition of dextran sulfate-induced prekallikrein activation , indicating that the impaired rate of contact activation in bovine plasma is due to the presence of inhibitors .
Diseases in which increased kinin formation has been documented as well as disorders where there is strong evidence for the activation of kallikrein are presented .
Activation of the coagulant pathway in cigarette smokers .
After inactivation of alpha 1-antitrypsin , ci inhibitor , and other plasma protease inhibitors with chci3 , plasma was incubated with kaolin , in the absence of added calcium , which limited the enzymes formed to those dependent on contact activation .
In addition , f1.2 , tat , activated f vii ( f viia ) and the activities of f ii , f vii , f x and protein c were measured in venous blood .
These findings showed that the proteins of the contact system were more extensively activated in ards than were the proteins that contribute to later reactions in intravascular coagulation and fibrinolysis .
Identification of fibronectin type i domains as amyloid-binding modules on tissue-type plasminogen activator and three homologs .
To find out whether changes within the hemostatic system are related to the severity of illness and organ failure in patients at the onset of clinically defined sepsis and to find some indications for the contribution of endothelial cell activation or perturbation to the patient's status .
Native and reduced sds polyacrylamide gel electrophoresis on the automated phastsystem ( pharmacia ) were used to demonstrate protein-protein binding interactions and structural changes during proteolytic activations of the proteins involved in contact activation .
These results demonstrate that both factor xii(a) and factor ix(a) directly activate human factor vii , whereas kallikrein , through generation of factor xii(a) and factor ix(a) , functions as an indirect activator of factor vii .
The contact system was not activated further by continuous venovenous haemofiltration using polyacrylonitrile filters in critically ill patients .
We conclude that a single injection of tumor necrosis factor elicits a rapid and sustained activation of the common pathway of coagulation , probably induced through the extrinsic route .
In conclusion , in the ascitic fluid of patients with cirrhosis , both bradykinin- ( 1-9 ) and bradykinin- ( 1-5 ) are present , with cleavage of high-m(r) kininogen and activation of fibrinolysis .
1. activated human plasma factor xiii was 65% inhibited by iodo[ ( 14 ) c]acetate and incorporated 0.6 mol of label into the alpha subunit , which eventually was allowed to form a precipitate. 2. all the label was recovered as s-carboxymethylcysteine in a tetra-peptide of sequence gly-gln-cys-trp .
Longitudinal study on activated factors xii and vii levels during normal pregnancy .
The chemokines are thought to interact with their receptors via two distinct sites , one necessary for binding and the other for activation of signal transduction .
Celite eluate was used instead of kaolin or dextran sulphate for the activation .
In the present study , suspensions of eosinophils and the supernatant fluid after eosinophils had been separated by centrifugation inhibited activation of hageman factor by ellagic acid .
The tests performed included bleeding time ( bt ) , platelet count , prothrombin time ( pt ) , prothrombin consumption index ( pci ) , activated partial thromboplastin time ( aptt ) , pf3 release with adenosine diphosphate ( adp ) at 0 and 20 min , total pf3 assay and platelet aggregation studies with collagen , adp , adrenaline , arachidonic acid and ristocetin .
The method is useful to the kinetic analysis of the surface-mediated activation of factors xii and xi , although it is not applicable to the activation in plasma .
185,000 ) and was specifically inhibited by an antiserum directed against activated pta .
Activation of the kinin system may therefore be involved in decompensating cirrhosis , but a cause-effect relationship remains to be established .
Questions have been raised about the role of hmwk in the activation of hageman factor by surfaces .
An aqueous extract from a mite culture , of dermatophagoides farinae , activated prekallikrein to kallikrein in normal plasma .
The aim of the present study was to further evaluate the functional role of the factor xiia catalyzed activation of plasminogen .
It was found that human blood plasma is adsorbed and the enzyme hydrolyzing n-benzoyl-l-arginine , is activated on the column .
Patients with ards caused by sepsis had more evidence of intravascular coagulation and fibrinolysis than did patients with trauma-related ards by having significantly ( p less than or equal to 005 ) increased prothrombin times , activated partial thromboplastin times , and fibrin degradation products , and decreased antithrombin iii concentration .
Mechanisms , markers and management of coagulation activation .
In sharp contrast , both activation rate and yield was found to be significantly attenuated at hydrophobic surfaces in the presence of plasma proteins .
(6) the activation of factor xi by factor xiia , however , is inhibited by the schistosomal inhibitor .
Dextran sulfate enhances activation of factor xi by thrombin 2000-fold ; part of this effect is due to autoactivation of factor xi by activated factor xi .
It appears that heparin is unable to prevent contact activation in_vivo as well as in_vitro .
Surprisingly , the activation of cell-associated hk .
Bismuth subgallate shortened the clotting time of whole blood , an action localized to an effect on the early steps of the intrinsic pathway ; bismuth subgallate did not accelerate the thrombin time or prothrombin time of normal plasma , but could be substituted for kaolin as an activator of coagulation in assays of the partial thromboplastin time .
Pk activation on ecv304 cells or matrix is blocked by antipain or sbti and corn trypsin inhibitor partially inhibits kallikrein formation .
Contact-phase activation persisted for the following 10 days , whereas the initially enhanced bradykinin generation normalized after 2 days .
A retrospective analysis of 7 patients with streptococcal toxic shock revealed isolated prolongation of the activated partial thromboplastin time , which returned to normal during recovery .
The inhibitor appears to be specific for the contact activation step of the intrinsic pathway .
Rgc1qr , however , had no effect on intrinsic coagulation in the presence of undiluted kaolin or ellagic acid , and under these conditions failed to shorten the activated partial thromboplastin time of factor viii or factor-ix-deficient plasma .
Antibodies to gc1qr , urokinase plasminogen activator receptor ( upar ) and , to a lesser extent , cytokeratin 1 ( ck1 ) block fxii binding to huvecs as determined by flow cytometry and soluble or solid phase binding assays .
Treatment of purified hf with dfp or filtration of hf through columns of sbti bound to agarose did not prevent its subsequent activation by ellagic acid .
Homozygous fxii knockout ( fxii(-)/(-) ) mice showed no fxii plasma activity and had a markedly prolonged activated partial thromboplastin time ( aptt ) .
The mechanisms of activation differ .
Ninety-one were eligible for the tipps coagulation activation sub-study and randomized .
The cleaved precursor activated single-chain hgf .
However , there is reason to suppose involvement of further mechanisms operating in pmn activation , since the elevated c3a-concentrations began to fall off while leucocyte count and pmn-elastase concentrations were still increasing .
The investigation focussed on the determination of factor xii-like activity ( fxiia ) as an indicator of contact phase activation in the supernatant phase and at the membrane surface after plasma-membrane contact using an incubation test cell .
A parallel increase in the intrinsic pathway of coagulation may be limited by elevated alpha-1-antitrypsin at the level of activated factor xi .
Activation of the plasma kallikrein/kinin system on endothelial cells proceeds by a physiological mechanism to initiate cellular fibrinolysis independent of plasmin , fibrin , and tissue-type plasminogen activator .
Maximal pk activation required the addition of 250 microm or 10 microm zn2+ to buffers containing bovine serum albumin ( bsa ) or gelatin , respectively .
The findings of activated fvii and high f1.2 , d-dimer , and lp(a) are not uncommon in patients with crvo .
The link between high-fat meals and postprandial activation of blood coagulation factor vii possibly involves kallikrein .
When purified ci inh was added to normal blood , it markedly reduced the activation of factor vii and the shortening of the pt in a dose-related manner .
In experiments in_vitro with normal human plasma , we observed that hematin and protoporphyrin activated factor xii-dependent pathways of coagulation and fibrinolysis , and that they generated kallikrein activity .
Thrombin-mediated activation of endogenous factor xi in plasma in the presence of physiological glycosaminoglycans occurs only with high concentrations of thrombin .
Furthermore , when normal plasma was first subjected to extensive contact activation by dextran sulfate , during which the hk was extensively degraded to components smaller than the light chain ( as assessed by western blotting ) , we observed greatly reduced displacement of fibrinogen .
Activation of kallikrein-kinin system in human plasma with purified serine protease from dermatophagoides farinae .
Contact activation seems to take place in spite of a high level of inhibition .
These results suggest that recombinant alpha 1-at ( met358----arg ) has therapeutic potential for disease states where activation of the plasma kinin-forming system is observed , for example in hereditary angioedema or septic shock .
Each domain as well as haemaphysalin inhibited intrinsic coagulation by inhibiting activation of the kallikrein-kinin system without affecting the amidolytic activities of intrinsic coagulation factors , indicating that both domains were involved in the inhibition through a similar mechanism to that for haemaphysalin .
Plasma kallikrein partially purified in a high and low molecular weight form exerted plasminogen activator activity amounting to 10-15 bau/ml plasma .
The kinetics of the enzymic reactions that participate in the contact activation system of human plasma were examined .
Thrombin , but not factor xa , also cleaved detectable amounts of factor xi in the presence of activated platelets .
The binding of activated fxii to the ecm suggests that fxiia may be a modulator of cellular adhesion , migration and vascularization .
Preincubation of factor xi with thrombin or factor xa , but without platelets , did not enhance thrombin generation , suggesting that these proteases might activate factor xi on platelet surfaces .
Administration of tranexamic acid to the patients resulted in partial normalisation of plasma kinin activation .
Resistance to activated protein c ( apc ) is usually linked to factor v leiden , but may occur in other disorders associated with hypercoagulability .
In a purified system , maximal pk activation was measured after a 10-15 min incubation depending upon the concentration of reactants .
We sought to determine if the administration of prophylactic doses of lmwh downregulates coagulation activation in high risk pregnant women with thrombophilia .
Amino acid sequence analysis of peptides obtained from fxii locarno on activation with either trypsin or plasma kallikrein and dextran sulfate showed an amino acid substitution of arg 353 by pro .
Comparing the catalytic constants of factor xiia with those of urokinase activation of plasminogen , the specificity constant , kcat/km , of factor xiia activation of plasminogen was 20-fold lower .
Activation of the contact system generates vasoactive mediators , which may play a role in the accumulation of malignant ascites .
Contaminated heparin associated with adverse clinical events and activation of the contact system .
Exposure to sct resulted in stable activation of the adenylate cyclase system which was noted for several hours after the removal of sct , sct may form a stable complex with the receptors , thus activating the catalytic unit of the adenylate cyclase for a substantial period of time after removal of the hormone .
We studied the activation pattern of clotting , fibrinolysis , and kinin-kallikrein during the first 5 d of life in 10 preterm infants with signs of severe idiopathic respiratory distress syndrome ( irds ) after birth ( irds group ) and in 12 healthy preterm infants ( reference group ) .
Neither plasma triglycerides nor kallikrein and activated fvii were statistically associated .
In contrast , plasminogen activator inhibitor activity was significantly higher ( 262 +/- 103 iu ; 2p < 001 ) among patients allocated simvastatin .
Accordingly , platelets may mediate physiological thrombolysis by this pathway since factor xiia activates pk and kallikrein activates pro-uk .
In this study , the plasminogen activator ( pa ) activity of fxiia was examined both in a purified system and in a dextran sulfate euglobulin fraction of plasma by measuring fibrinolysis in a fibrin microtiter plate assay .
Similar to the results in plasma , activation of prekallikrein , hmwk present , by factor xiia bound to kaolin , was inhibited approximately 70% by 13g11 .
In patients with apl , treatment with either chemotherapy or atra rapidly ameliorates the coagulopathy , as indicated by an abrupt decline in markers of clotting activation .
The activated forms of hageman factor , hfa and hff , were also inactivated by ppacmk with rate constants 0.82 and 0.72 min-1 .
Conclusion. our results suggest that plasminogen is frequently activated in the joints of patients with inflammatory or noninflammatory arthropathy and that this activation mainly occurs via a u-pa- , and in some cases also via a factor xii- , dependent pathway .
Activation of the coagulation system in polycythemia vera .
Bradykinin ( bk ) , an important mediator of allergic reactions and pain induction , is released by the activation of the plasma kallikrein-kinin ( k-k ) cascade .
Antithrombin iii inhibition of activated hageman factor is augmented by heparin which is also an activator of hageman factor .
Thus , markers of coagulation activation may be useful in stratification of patients when estimating risk for adverse clinical outcome after ami .
Ecotin and variant ecotins are subnanomolar inhibitors of the mt-sp1 activated protease domain , suggesting a possible role for mt-sp1 in prostate differentiation and the growth of prostatic carcinomas .
Based on these results , we conclude that plasma cl(-) -inh complex levels during sepsis may not properly reflect the extent of contact activation .
Oscs-containing heparin and synthetically derived oscs induced hypotension associated with kallikrein activation when administered by intravenous infusion in swine .
It is the aim of the present study to prove that heppg or glycosaminoglycan derived from human mast cells is also capable of acting as a physiologic macromolecule and to induce contact activation .
Platelets in turn are activated primarily by thrombin , collagen , and , in a self-perpetuating process , since all these materials are released from activated platelets , also by adenosine-5-diphosphate , adrenaline , and serotonin .
These results suggest increased activation of both fvii and fxii in hyperlipidaemic subjects , which correlates with increased thrombin generation .
Zinc-dependent activation of the prekallikrein-hk complex also depended on addition of either alpha and beta isoforms of hsp90 and the activation on endothelial cells was inhibited on addition of polyclonal ab to hsp90 in a dose-dependent manner .
Substrate specificity of activated factor xi and inhibition profile of activated factor xi against proteinase inhibitors were investigated by comparison with those of bovine and human activated factor xi .
It appears that an acid-induced conformational change of the prorenin molecule is not required for its activation by plasma kallikrein .
Activation and inhibition of hageman factor-dependent pathways and the complement system in uncomplicated bacteremia or bacterial shock .
Kaolin-induced writhing response in mice : activation of the plasma kallikrein-kinin system by kaolin .
Previously we studied levels of the cytokine il-6 and activation of the complement and contact system and of neutrophils in a group of 48 patients with sepsis .
While this system is essential for minimizing blood loss from an injured blood vessel ( hemostasis ) , it also contributes to pathologic fibrin formation and platelet activation that may occlude vessels ( thrombosis ) .
The results showed that surface-bound hageman factor was 500 times more susceptible than soluble hageman factor to proteolytic activation by kallikrein in the presence of high molecular weight kininogen .
Reactions requiring all 4 contact phase factors , including pta , such as surface-induced generation of plasmin activity ( amidolysis of h-d-val-leu-lys-pna ) and activated christmas factor ( factor ixa ) activity , were defective .
In the absence of cofactors , thrombin is more effective ( kcat/km = 1.6 x 10(5) ) than factor xiia ( 1.7 x 10(4) ) in activating factor xi .
Increasing the level of cell-bound kallikrein increased the portion of cell-bound pro-u-pa activated , indicating that their co-localization was important for this pathway .
The dextran sulfate ( ds ) cellulose column usually used for low-density lipoprotein ( ldl ) apheresis , is an activator of the contact phase of intrinsic coagulation pathway .
We have analyzed the influence of plasma lipoproteins on the activation of the contact pathway of blood coagulation in platelet-rich plasma ( prp ) .
Apart from tissue-type plasminogen activator ( t-pa ) and urokinase-type plasminogen activator ( u-pa ) , a third pa appears to occur in human plasma .
The exposure of rats to 100% oxygen at 1 atmosphere leads to a prolongation of prothrombin times and activated partial thromboplastin times .
Bismuth subgallate , which is an insoluble analog of ellagic acid , lost its ability to activate hageman factor on being exposed to bac770 .
These results strongly suggest that activation competes with an autoinhibition reaction in which fxiia itself inhibits fxii-- > fxiia .
We studied the effect of heparin on the activation of factor xi by fibrin-bound thrombin .
Prognostic value of assessing contact system activation and factor v in systemic inflammatory response syndrome .
Absence of paradoxical thrombin activation by fibrin-specific thrombolytics in acute myocardial infarction : comparison of single-bolus tenecteplase and front-loaded alteplase .
Tissue plasminogen activator antigen ( t-pa ag ) levels were increased in group 2 ( 282 ng/ml ) compared both with group 1 ( 85 ng/ml ) and controls ( 59 ng/ml ) .
These data suggest that fondaparinux enhances the antithrombin-dependent downregulation of the tf pathway by decreasing the generation of fviia via the inhibition of the generation and the activity of activated factor ix and activated factor x , and by inhibiting the activity of the fviia-tf complex .
Both schistosome extracts and secretory products inhibited the activation of purified hageman factor by more than 95%. schistosome extracts inhibited activation of hageman factor both by ellagic acid and by bovine sulfatides .
An investigation of a new activated clotting time "max-act" in patients undergoing extracorporeal circulation .
Addition of heparin to plasma prior to surface exposure did not prevent activation of surface-bound fxii , nor did it increase the beta-fxiia inhibition rate and prevent fxi activation in plasma , although beta-fxiia and fxia-at complex formation occurred .
An embryo-derived platelet activating factor has been demonstrated to play an important role in reproduction .
We propose that independent mechanisms for bypass of factors xii and xi are important in physiologic activation of coagulation .
The intrinsic pathway of blood coagulation is activated when factor xia , one of the three contact-system enzymes , is generated and then activates factor ix .
These findings suggested that noticeably activated states of coagulation , fibrinogenolysis and fibrinolysis exist in normal pregnancy .
The concentrations of tissue factor , tissue factor pathway inhibitor , factors xii , x , vii , and i , prothrombin fragment f1 + 2 , and thrombin-antithrombin complex as well as platelet count , prothrombin time , activated partial thromboplastin time , plasmin-antiplasmin complex ( pap ) and d-dimers were measured .
We did not detect activation of the extrinsic coagulation pathway after decompression .
No increase in hageman factor enzymatic activity was detected after incubation with tryptase at 37 degrees c ; activation of hageman factor by bovine trypsin served as a positive control .
These studies indicate that hageman factor has a hitherto unsuspected function , the direct activation of plasminogen .
Five commercially available activated partial thromboplastin time ( aptt ) test systems were compared with the kaolin partial thromboplastin time ( kptt ) method to determine sensitivity in detecting minor coagulation defects .
Fxii activity was measured by an activated partial thromboplastin time ( aptt ) assay .
There may exist a ripe3b1 activator binding site in the glucose-responsive element from -1138 to -880 bp .
In those < or =55 years d-dimer was inversely associated with dilute clot lysis time ( dclt ) and activated protein c ( apc ) ratio .
These data suggest that reactive oxygen species may be involved in the activation of nf-kappab induced by silica .
These results alone do not explain the cold promoted activation , since a patient with a c1-inhibitor as low as 9% showed no increase of the amidolytic activity after a 24 hr incubation at 4 degrees c. however , the addition of purified c1-inhibitor to a cpa pos .
Bradykinin , the end product of activation of the plasma contact system , may play a significant role in reactions to contrast material and in other forms of anaphylactoid and anaphylactic responses to drugs or antigens .
It is initiated by a fast contraction of the molecule upon binding , as revealed by an apparent increase in organized secondary structures , and then followed by a slow relaxation process during cleavage and subsequent activation .
Further , (i) adding highly purified coagulation fxii , alpha fxiia , or beta fxiia fragment restores pressor activity to such plasmas , but only after activation with trypsin. ( ii ) such requirement for trypsin suggests that no factor is structurally identical with npp to begin with but that all can be activated to npp. ( iii ) when injected directly by vein , only beta fxiia is pressor , suggesting closest structural resemblance to npp and ( or ) readiest endogenous conversion to npp. ( iv ) npp and beta fxiia are cardiotonic : .
The presence of benzamidine 0.7 to 2.1 mm during acetone treatment increased the measured level of fxii assayed both as prekallikrein activator and as s-2222 amidase .
Activation of the contact system proteins could be the result of endothelial injury occurring as part of ards .
Activation is also inhibited by alteration of the other two basic amino acid residues present , lysine and histidine .
From this study and our previous investigations on the effect of heparin on the inhibition of kallikrein and factor xia , we conclude that heparin does not significantly affect the protease activity of purified contact activation factors or the activities expressed by these proteases in plasma .
These studies indicate that fibrinogen specifically binds to the c3r receptor on the neutrophil surface through the carboxy terminal of the gamma-chain and that hmwk interferes with the binding of fibrinogen to integrins on both neutrophils and activated platelets .
When citrated edta-treated plasma was activated with acetone-incubated normal plasma containing prekallikrein activator ( factor xiif ) , no significant difference in baee esterase activity was noticed between plasma from the patients and that from the control persons .
Activation of purified human plasma prekallikrein triggered by cell wall fractions of escherichia coli and staphylococcus aureus .
The effects of high-mr kininogen and kaolin surface on the kinetics of these activation reactions were studied .
The contact activation hypothesis describes the assembly and activation of this system in test tubes and disease states , but not under physiologic circumstances .
Investigators have long searched for physiologic activators of fxii and its role in_vivo .
The yield of activated pta was proportional to the amount of hf , hmw-kininogen , and pta in the mixtures , suggesting that , to activate pta , these three proteins might form a complex in the presence of ellagic acid .
Physiological concentration of factor xiia was as more efficient than soluble u-pa to lyse fibrin as a result of activation of glu-plasminogen .
Normal plasma activated with celite had significantly prolonged onset and duration of clot lysis compared with samples activated with tf .
Activation of the intrinsic pathway , thrombin generation , fibrin formation and fibrin degradation may be present in patients with ami just after the onset of coronary thrombus formation .
The adsorbed fibrinogen will be replaced on glass-like surfaces during surface activation of clotting , and platelets failing to find fibrinogen will not adhere .
This analysis supported the conclusion that plasma kallikrein-mediated cleavage and activation of single-chain u-pa is the mechanism operative for the development of lytic activity in euglobulin precipitates following activation of the contact system .
High molecular weight kininogen regulates prekallikrein assembly and activation on endothelial cells : a novel mechanism for contact activation .
The available evidence suggests strongly that intravascular thrombosis is mediated predominantly by tissue-factor and its activation of factor x , which in the presence of factor va , calcium , and phospholipid ( prothrombinase complex ) effectively converts prothrombin to thrombin .
The direct activating site of forskolin appears to reside in a protein which is closely associated with the catalytic unit of adenylate cyclase system and has a relatively shorter half-life than other components of the system .
In contrast , since addition of cationic proteins to collagen markedly reduced pro-coagulant activity it is suggested that negatively charged sites on the collagen molecule are critical for hageman factor activation .
This finding may be significant since adsorbed proteins may activate coagulation mechanisms and immunologic responses , including platelet and monocyte adhesion and activation .
The yield of activated pta was proportional to the amount of hf , hmw-k , and pta in the mixtures , suggesting that these three proteins may form a complex in the presence of ea .
By the end of this phase , kallikrein (k) is completely inhibited , residual activity of factor xiia is 54% , and factor xi is activated by 26%. once a clot is formed , factor ii is activated by 4% , factor x by 5% , factor ix by 90% , and factor xi by 39%. calculated clotting time using protein concentrations found in the blood of healthy people was 40.5 s. the most pronounced prolongation of aptt is caused by a decrease in factor x concentration .
The capability of these recombinant proteins to bind to negatively charged surfaces and to initiate contact activation was studied .
There is also a factor xii-independent bypass mechanism requiring a cell-derived cofactor or protease that activates prekallikrein .
Surface activation of blood coagulation , fibrinolysis and kinin formation .
On endothelial cells , prekallikrein is activated by an antipain sensitive protease .
Tumor necrosis factor has been implicated in the activation of blood coagulation in septicemia , a condition commonly associated with intravascular coagulation and disturbances of hemostasis .
The coagulation and fibrinolytic systems are activated more intensively with cellulose acetate and more prolongedly with polyacrilonitrile .
The role of fragment 1 ( f1 ) in the pathway of exosite i expression during pro activation was characterized in equilibrium binding studies using hirudin ( 54-65 ) labeled with 6- ( n- ( 7-nitrobenz-2-oxa-1,3-diazol-4-yl ) amino ) hexanoate ( [nbd]hir ( 54-65 ) ( so3- ) ) or 5- ( carboxy ) fluorescein ( [5f]hir ( 54-65 ) ( so3- ) ) .
Activated factor vii and f ( 1+2 ) levels were correlated ( r = 0529 ; p = 008 ) .
The inverse relationship between a small patient's blood volume and the large pump-prime volume requires additional aprotinin to be added to the prime to achieve plasma levels sufficient to inhibit activation of the coagulation cascade .
This phenomenon may contribute to maintaining the fluidity of circulating blood by inhibiting surface activation of the intrinsic pathway of coagulation .
Acute , acalculous cholecystitis is seen among patients suffering with bacterial sepsis , burns , trauma , or cancer ; clinical conditions that could lead to activation of factor xii-dependent pathways and result in inflammation of the gall bladder .
The well-iron efficacy of the activated partial thromboplastin time for detecting coagulation abnormalities is counter-balanced by some disadvantages such as the delay for biologic conclusions .
Prothrombin is a cofactor for the binding of factor xi to the platelet surface and for platelet-mediated factor xi activation by thrombin .
Lethal infection with r. conorii is associated with primary endothelial cell injury resulting in decreased tissue plasminogen activator and increased plasminogen activator inhibitor .
Similar experiments with kaolin showed that with limiting amounts of activator ( 1-2 mg/ml ) , only kallikrein-c-1-inh complexes were detected in plasma .
Non-fibrillar betaa1-42 , and truncated peptide 1-28 , induced dose-dependent activation of c4 sparing c3 .
The significance of the activation of the intrinsic system is seen in the possibility of the initiation of a self-sustained process which , after a primary event , e.g. vascular or cellular injury , will continue to convert prothrombin into thrombin .
The hypothesis that heparin-coated perfusion circuits reduce thrombin formation and activity ; fibrinolysis ; and platelet , complement , and neutrophil activation was tested in 20 consecutive , randomized adults who had cardiopulmonary bypass .
Coagulation system and platelets are strongly activated in sepsis .
When blood is exposed to negatively charged surface materials such as glass , an enzymatic cascade known as the contact system becomes activated .
Initiation of contact activation may involve proteolytic activation of surface-bound hageman factor by a number of different proteases .
In summary , our work demonstrates that mmp-1 zymogen activation is mediated by multiple serine proteases and mmp-10 , and that these events are central to ec-mediated collagen degradation and capillary tube regression in 3d collagen matrices .
V2-renal receptors stimulate the production of cyclic amp which activates protein kinase a. subsequently , the actin network is altered and particles containing pores agregate at the cell surface to produce water molecules reabsorption .
Tissue-plasminogen activator , urokinase-plasminogen activator and plasminogen activator inhibitor did not change significantly .
This study evaluated whether an oxygenator coated with poly 2-methoxyethylacrylate ( pmea ) ( x-coating ; terumo corporation , tokyo , japan ) would cause less activation of coagulation and fibrinolytic systems during cpb in children than a noncoated oxygenator .
Celite activation of tafi-deficient/fxiii-supplemented plasma showed significantly prolonged onset and duration of clot lysis compared with samples activated with tf .
Thus , fxiia is not only involved in the activation of the coagulation system , but is also associated with the kallikrein/kinin system .
High molecular weight kininogen ( hk ) is a co-factor in the blood-contact activation system .
Mechanisms of activation of the intrinsic coagulation system and its role in oxygen toxicity are being discussed .
Incubation of the activated mixture with 3h-dfp followed by reduced sds-page showed the active site to be associated with a unit of mr = 44,500 .
Unchanged kallikrein levels confirmed that no interaction between prorenin activation and factor xii-kallikrein system appears to be present .
In contrast , plasma levels of plasminogen activator inhibitor ( pai ) were modestly enhanced in the treatment group .
This study suggests that irreversible hypotension correlates with prolonged activation of the contact system .
The contact activation system : biochemistry and interactions of these surface-mediated defense reactions .
The application of chromogenic peptide substrates for analysing the early stage of clotting has to take into account the special mechanisms of activation .
Endothelial cells , perhaps stimulated by formation of minute quantities of thrombin , produce tissue plasminogen activator , which generates plasmin , a fibrolytic enzyme .
In the presence of factor xi , additional fibrin formation was observed indicating that factor xi activation by thrombin in complex with fibrin and heparin can take place in plasma .
Antiphospholipid antibodies in pediatric patients with prolonged activated partial thromboplastin time during infection .
Further , thrombelastographic analyses that include the addition of tissue-type plasminogen activator have demonstrated that contact protein pathway activation results in thrombin activatable fibrinolysis inhibitor activation to a far greater extent than that observed with tissue factor initiated coagulation , resulting in a thrombus that takes significantly longer to lyse .
Activation of the intrinsic pathway of coagulation in children with meningococcal septic shock .
Peptide fxii39-47 inhibited the binding of labeled fxii to kaolin and effectively prevented both dextran sulfate - and kaolin-induced activation of the contact system in plasma .
This prospective study of a natural clinical model indicates a cause-effect relationship between formation of igg-vwf complexes and massive complement activation in posttransfusion non-ige-mediated anaphylactic reactions.
Objectives : the aim of this study was to characterize abnormalities of coagulation in mice with experimental , invasive group a , streptococcal shock , in an attempt to explain the prolongation of the activated partial thromboplastin time identified in patients with streptococcal toxic shock syndrome .
High molecular weight kininogen ( hmwk ) functions as a cofactor for activation of plasma serine zymogens and as an inhibitor of tissue cysteine proteases .
Hepatocyte growth factor activator ( hgf activator ) is a serine protease which converts single-chain hgf to the active two-chain form .
At ph 6.5 or 7.3 , however , the plasminogen activator inhibitor production decreased and tissue-type plasminogen activator production increased in a glucose concentration-dependent manner .
Patients treated with aprotinin require approximately 20% less heparin to achieve an activated clotting time ( act ) of 400 s than control patients .
The cause must be searched in the observed increase of plasminogen-activator-inhibitor ( pai ) --likly in combination with a decrease of the tissue-type plasminogen activator ( t-pa ) .
Nicked beta2gpi binds to plasminogen and suppresses plasmin generation in the presence of fibrin , plasminogen , and tissue plasminogen activator ( tpa ) .
Hgf is homologous to plasminogen and is first synthesized and secreted as an inactive single-chain precursor and then activated to a heterodimeric form by endoproteolytic processing .
The findings confirm the importance of this alternative pathway in leading to activation of factor vii .
However , neither clq-deficient serum nor a truncated form of gc1qr ( gc1qra74-96 ) , supported complement activation .
Activated factor 12 ( fxiia ) predicts recurrent coronary events after an acute myocardial infarction .
Confocal microscopy studies show that when platelet integrins contact plasma protein-saturated pglcnac fibers , an increase in intracellular free calcium for platelet activation occurs to drive surface expression of phosphatidyl serine ( ps ) .
There were no significant increases or decreases in the cleaved kininogen index ( cki ) , an index of hk proteolytic activation or hk and lk destruction ( with release of bradykinin ) .
From these results the conclusion was drawn that activation of fibrinolysis by polysulfated polysaccharides is achieved by an endogenous pathway as well as by an increased availability of the vascular activator .
The data indicate that complement activation during cpb correlates poorly with neutrophil activation and that either kallikrein or fxiia or both may be more important agonists .
When the activating enzyme and the activated enzyme coincide , the process is an autocatalytic zymogen activation .
Except for a somewhat higher platelet count during cpb , there was no indication that pmea coating resulted in less activation of coagulation and fibrinolytic systems .
Contact activation of plasma prekallikrein ( ppk ) assayed by a tripeptide chromogenic substrate , and surface-mediated fibrinolysis by the euglobulin test ( both tests being insensitive to the anticoagulant effect of heparin and heparinoids ) were studied .
Peptide yhk9 also inhibits fxiia's activation of prekallikrein and fxi on huvecs .
To investigate the role of activated protein c resistance ( apcr , factor v leiden ) in coronary artery thrombosis .
This study describes a novel biologic surface for fxii activation and activity , which initiates inflammatory events independent of hemostasis .
The addition of purified activated beta-xii led to a complete restoration of fibrinolysis in homozygotes .
Elaboration of agents inhibiting hf activation required metabolically active cells .
One of the suggested receptors of this binding is the glycosylphosphatidylinositol-anchored urokinase-like plasminogen activator ( u-par ) harbored in caveolae/lipid rafts .
In the retrospective part of the study , cases of plasma resistance to activated protein c were not abnormally frequent .
Whether activation of factor xi by triglyceride rich lipoproteins initiates these reactions needs to be demonstrated in future studies .
Inhibition of endothelial cell-dependent prekallikrein activation required 100-fold greater concentration of ldc27 when compared to hkh20 to achieve significant inhibition .
Improved coagulation screening by an activated recalcification test .
Apolipoprotein b-100 of plasma low density lipoproteins undergoes proteolysis by contact activation factors when plasma is treated with dextran sulfate-500-mgcl2 .
The activation of xii was studied in fresh plasma as well as in plasma stored for 3-6 months at -70 degrees , and the activation with acetone was carried out in the presence and in the absence of benzamidine , edta or purified hmrk .
A modified activated partial thromboplastin time assay for cac has been defined by using a substrate of dicalite-adsorbed plasma combined with partially purified sources of factors xi and xii , and fletcher factor .
Furthermore , yap did not possess plasminogen activator-like activity to activate fibrinolysis .
Bk from kininogens is a potent modulator of vascular biology inducing vasodilation , tissue plasminogen activator release , and prostacyclin liberation .
After clotting , activated factor ix ( ix(a) ) was the apparent principal activator .
H-kininogen ( hk ) , a major factor involved in contact-phase activation , was recently immunolocalized on the external surface of human neutrophils .
Plasma prekallikrein :quantitative determination by direct activation with hageman factor fragment ( beta-xiia ) .
Transdermal estradiol therapy for prostate cancer reduces thrombophilic activation and protects against thromboembolism .
Its smallest unit ( sds-page ) is an inactive 110 kda single-chain polypeptide which upon activation of the contact system is converted to a cleaved , disulphide-bridged molecule with pa activity .
Activation of both the intrinsic system and tissue mediators contribute to the vasomotor phenomena in carcinoid syndrome and postgastrectomy dumping .
The effect of f1 on ( pro ) exosite i and the role of ( pro ) exosite i in factor va-dependent substrate recognition suggest that the pro activation pathway may be regulated by ( pro ) exosite i interactions with factor va .
Alterations of the kallikrein-kinin system consistent with activation and increased consumption have been reported in septic patients and it has been suggested that this activation could contribute to the development of septic shock .
These results suggest that the activation of factor xi by thrombin and possibly the autoactivation of factor xi proceed in plasma to lead fibrin clot formation .
Hae results from functional deficiency of the c1 inhibitor ( c1inh ) protein , which plays a key role in the classical pathway of complement activation .
In this purified system , in contrast to earlier studies using crude systems , platelet factor 4 inhibited activation of hageman factor by glass , ellagic acid , or kaolin .
High levels of factor viii and low levels of antithrombin imply that the coagulation system could be more easily activated when other factors coincide , e.g. intimal lesions in carotide arteries .
In this study , we identified the precursor of hgf activator in human plasma using an enzyme-linked immunosorbent assay system .
On the other hand , exposure of plasma containing uroporphyrin or coproporphyrin to ultraviolet light did not result in activation of factor xii-dependent pathways .
In contrast , activation of purified fxii in a plasma-free system with respect to supernatant activity indicated significant differences between the materials .
Human blood plasma lost the capacity to contact activation after chromatography on a column with noradrenaline-sepharose .
They also reduced the activity to the level seen with pk activation alone .
Factors affecting the rate of contact activation in human plasma .
Here we report that intact s. aureus bacteria activate the contact system in human plasma in_vitro , resulting in a massive release of the potent proinflammatory and vasoactive peptide bradykinin .
The kinetics of prekallikrein activation and the effects of inhibitors provide evidence that the amidolytic and proteolytic activities of human hageman factor reside in the activated forms derived by limited proteolysis of the native molecule .
The delay between the maximal activation of factor x and that of prothrombin amounted to several hours , indicating that neutralization of factor xa activity was slow .
In the case of kaolin-mediated activation , la3 was the most potent inhibitor , while platelet factor 4 and beta-tg-like substance did not show any significant inhibitory activity .
Apc resistance was measured as the ratio of activated partial thromboplastin times with and without apc ( apc-sensitivity ratio , apc-sr ) .
Kinin activation as a predictive assay for adverse reactions to radiographic contrast medium .
Does kallikrein activated by acetone-treatment of plasma exist in modifications with different abilities to associate with fxii? and will -70 degrees storage of plasma increase the liability to complex formation? s-2302 amidase assays carried out in mixtures of normal plasma and plasma genetically deficient in prekallikrein ( pk ) suggested an inhomogeneity of the kallikrein generated .
Tnk-tpa consecutively has no paradoxical systemic procoagulant effect due to the lower extent of activation of the kallikrein-factor xii system than alteplase .
Using recently developed sensitive assays for fxia-inhibitor complexes we found thrombin-mediated and fxii-dependent activation of endogenous fxi in plasma in the presence of heparan sulphate , heparin , dermatan sulphate or dextran sulphate .
For establishing the optimal incubation time ( oit ) for measurement of the activated partial thromboplastin time ( aptt ) in dogs , rabbits , guinea pigs , rats and mice , we determined the shortest clotting time of the plasma from each animal species and compared them with that of human plasma .
Heterozygous fv : q506 ( n = 5 ) , homozygous fv : q506 ( n = 2 ) , homozygous fxii deficiency ( n = 1 ) , protein c deficiency type i ( n = 5 ) , protein c deficiency type ii ( n = 1 ) , antithrombin deficiency type i ( n = 1 ) increased lp (a) ( n = 5 ) , activated protein c-resistance without mutation in the fv gene ( n = 2 ) , and increased anticardiolipin igg antibodies ( n = 2 ) were diagnosed in the children investigated .
The contact-system dependent plasminogen activator from human plasma : identification and characterization .
Hageman factor , hmrk and prekallikrein were required for maximal rates of activation of factor xi .
Although we confirmed that hmw kininogen , bovine serum albumin , fibrinogen , cold insoluble globulin , and mixed phospholipids apparently increased prekallikrein activation , we found that the product of prekallikrein activation ( kallikrein ) lost substantial activity in less than 0.5 min after exposure to a variety of fresh surfaces .
The intron/exon gene organization is similar to the serine protease gene family of plasminogen activators and not to the clotting factor family .
Despite continuously defective c1-inh levels , symptoms only recur occasionally suggesting an episodic generation of pathogenetic factors induced by activation of the protease systems regulated by c1-inh .
Fluctuations in levels of antiphospholipid antibodies and increased coagulation activation markers in normal and heparin-treated antiphospholipid syndrome pregnancies .
Tissue plasminogen activator and plasminogen activator inhibitor-1 antigen levels were associated positively with chd incidence in analyses adjusted for age , race , and sex but were not associated with chd after adjustment for other risk factors .
Acetylcysteine in rats : inhibition of activation of prekallikrein and factor xii--protection against dextran-induced blood pressure fall .
The patient presented with a severe , apparently spontaneous bleed into the thigh , which progressed despite infusion of fresh frozen plasma , but which responded promptly to activated prothrombin complex .
Similarly activated rat citrated plasma ( rcpl ) revealed on gel filtration an additional esterase peak ( mol wt , approximately 47,000 ) with a low kininogenase-esterase ratio ( 03 ) , and should accordingly not be used for a baee-esterase assay of rat plasma kallikrein .
Furthermore , it is found that surface activation is moderated by the protein composition of the fluid phase in which fxii autoactivation occurs by what appears to be a protein-adsorption-competition effect .
Diisopropyl fluorophosphate treatment of plasminogen did not inhibit its activation by hageman factor .
Factor xi : purification from porcine plasma by affinity chromatography and some properties of factor xi and activated factor xi .
Platelet factor 4 and beta-thromboglobulin increases suggest platelet activation , only partially dependent on arachidonic acid-mediated pathway as thromboxane b2 is not increased .
Urokinase-type plasminogen activator ( u-pa ) was found to induce monocyte adhesion through a u-pa receptor ( u-par ) -mediated camp-dependent signal transduction pathway ( j biol chem 270 , 30282-30285 , 1995 ) .
Investigations determined if extracellular matrix of endothelial cells ( ec ) is a platform for hk assembly and pk activation .
Extensive contact activation of factor xi-deficient plasma failed to show low-mol-wt derivatives , however , and displacement of fibrinogen was similar to normal plasma that had not undergone extensive activation .
Increases in coagulant ( activated partial thromboplastin time ) and fibrinolytic ( tissue type plasminogen activator activity ) potential proceeded in parallel during exercise .
This may provide a rational interpretation for the observation that patients with hemophilia a and b bleed even though they appear to have an alternative pathway to factor x activation .
Factor xi activation in a revised model of blood coagulation .
After acetone activation plasma kallikrein was assayed as plasminogen activator , baee esterase or s-2302 amidase , and factor xiia was assayed as kaolin-activated prekallikrein activator .
These results together indicate that amino acid residues 3-19 of fxii are involved in the activation of factor xi and do not contribute to the binding of fxii to negatively charged surfaces .
The least activating surfaces , affecting both free plasma and surface-bound factor xiia , were those treated with platelet membrane glycoprotein fragment and glucose .
Thrombin generation and activation become marked in patients with unstable angina pectoris or acute myocardial infarction .
This demonstrated the strong influence of heparin and the interaction of other plasma components to the membrane surface on the activation of contact phase of coagulation .
It was independent of contact factor activation , and appeared to be related to the sulfonated groups of the polymer .
These experiments demonstrate that ellagic acid can activate hf in a manner analogous to negatively charged solids such as glass or kaolin .
Indirect approaches to the detection of coagulation activation are to measure the plasma levels of peptides released from coagulation zymogens when they are converted into active enzymes and the stable complexes formed in plasma when such enzymes are neutralized by their naturally-occurring inhibitors .
Seven women were found to have reduced fxii activity ( 19 2-461% ) and prolonged activated partial thromboplastin time ( 33 3-513 s ) .
Biophysical investigation of the structural basis of activation , substrate specificity , and regulation of fxii requires an efficient bacterial system for producing the wild-type and mutant recombinant proteins .
The ability of activation fragments of human prothrombin to inhibit binding of labeled prothrombin to its antibody was evaluated by competitive radioimmunoassay .
We conclude that the activation of coagulation is accompanied by an activation of fibrinolysis in the microcirculation , but that systemically the increased inhibitors of fibrinolysis ( pai , alpha 2-antiplasmin ) induce a decrease of the fibrinolytic capacity of the blood .
A high-concentration medium was developed for the high-density cultivation of chinese hamster ovary ( cho ) cells to produce tissue plasminogen activator ( tpa ) .
These data suggest that asp induces vl through prekallikrein activation and direct kinin release from kininogens , which is a previously undescribed mechanism of a. sobria virulence and could be associated with the induction of septic shock by infection with this bacterium .
This finding seemed to indicate that adsorption of factors xii and xi to larger particles during the activation process might protect these factors from inactivation by naturally occurring plasma inhibitors .
Therefore , contact activation is not likely to contribute to the hypercoagulability seen in these patients .
An increased ratio of surface area over plasma volume resulted in reduced contact activation , suggesting that plasma components are the limiting factor .
(i) high-affinity c1q binding and cell production of proinflammatory factors , and ( ii ) high-affinity hk binding and facilitation of the assembly of contact activation proteins leading to generation of bradykinin and possibly coagulation through activation of fxi .
This shortening is related to the activation of the contact phase of blood coagulation .
In_vitro studies suggested that streptococcal supernatants can activate prekallikrein , in addition to causing plasminogen activation through the action of streptokinase .
Contact activation prolongs clot lysis time in human plasma : role of thrombin-activatable fibrinolysis inhibitor and factor xiii .
Fxii adsorption competition with other proteins in the fluid phase is proposed to affect the balance of activation and autoinhibition , leading to the observed moderation of fxiia yield .
Both the cs and aza groups exhibited significant elevations of factor ix activity , von willebrand factor ( vwf ) , d-dimer , protein c and tissue type plasminogen activator ( t-pa ) levels when compared with the normal controls .
However , there may be a pathway of plg activation in this patient via the prekallikrein c1-inh system .
Activation of porcine f. xii-2 by porcine plasma kallikrein was found to involve the cleavage of the peptide bond on the disulfide-bridged polypeptide chain , and further fragmentation of activated form was observed during prolonged incubation time .
Endothelial cell-associated kallikrein also is capable of kinetically favorable pro-urokinase and , subsequent , plasminogen activation .
Isolation from human plasma of a plasminogen activator identical to urinary high molecular weight urokinase .
A new sensitive assay for bovine activated factor xi ( factor xia ) using a reconstituted coagulation cascade system .
Plasma kallikrein was strongly associated with triglycerides in fasting and non-fasting samples ( r2 = 074-087 , p < 00001 ) , suggesting that triglyceride-rich lipoproteins may activate prokallikrein .
Thus , it appears that in the present study pta was activated in two distinct ways .
To assess coagulation cascade activation as a potential index of thromboembolic risk in inflammatory bowel disease ( ibd ) .
In addition , our data suggest that large numbers of adherent platelets to the collagen surface promote activation of the intrinsic coagulation system .
This may cause activation of the complement system and release of bradykinin and pmn-elastase and could contribute to the pathogenesis of severe malaria .
Proteolytic activation of prekallikrein by purified human beta-factor xiia ( mr 28 000 form ) resulted in the formation of kallikrein .
Maximum activation occurred at 1-10 mm p(i) and approximately 25 microm zn ( ii ) .
Using the inactive precursor form of plasma kallikrein ( prepk ) as a substrate , we purified an enzyme capable of activating this protein .
Fibrinolysis was measured before and after dextran sulphate mediated contact activation using fibrin plates .
Provided that thrombin-mediated factor xi activation plays an important role in_vivo , danaparoid and especially the pentasaccharide may be better anticoagulants than ufh and lmwh .
The results also indicated that prekallikrein activator activity was connected with this fraction .
Activation of the plasma kallikrein/kinin system on endothelial cell membranes .
This heparin-binding domain may block the activation of hageman factor by negatively charged agents .
These observations suggest a greater susceptibility to activation of the fibrinolytic pathways during oca medication .
The inactivated activated pta ( factor xia ) without the requirement for an additional cofactor .
Using thrombelastographic-based analyses , it has been determined that contact pathway protein activated coagulation results in a thrombus that develops strength at a significantly faster rate that tissue factor initiated coagulation .
Prorenin-renin conversion by the contact activation system in human plasma : role of plasma protease inhibitors .
Characteristic structural domains in the nh2-terminal region of the zymogen may be involved in the binding of the zymogen to negatively charged substances , which stimulates the activation of the zymogen by thrombin .
Clotting activation was accompanied by a significant decrease of the platelet count .
To assess the physiological relevance of these findings we studied the activation of factor xi in normal and factor xii-deficient plasma .
We and others have demonstrated that tissue plasminogen activator ( t-pa ) and prourokinase are modified by the attachment of fucose to equivalent threonine residues within their egf domains .
Finally , f.xiia was shown to trigger plasminogen activation on huvec via this pathway .
After blood sampling , molecular activation markers of coagulation ( prothrombin fragments 1 and 2 , fibrinopeptide a , thrombin-antithrombin complexes , and monomers of fibrin ) and of platelets ( beta-thromboglobulin and platelet factor 4 ) , several coagulation factors , global tests of coagulation ( prothrombin time and activated partial thromboplastin time ) , and platelet count ( ptl ) were measured .
Addition of 320-640 nm of thrombin to factor ii deficient plasma resulted in the same amount of tafia as in normal plasma , suggesting that approximately 50% of factor ii has to be converted to thrombin for extensive activation of tafi .
These results indicate that phbp participates not only in the fibrinolytic system but also in the degradation cascade of extracellular matrix ( ecm ) , i.e. , phbp activates scupa to tcupa , tcupa activates matrix metalloproteases ( mmps ) and activated mmps degrade ecm for the tissue remodeling after hepatic injury .
Adp-induced platelet activation was greater in blood anticoagulated with heparin compared with an equipotent anti-xa concentration of enoxaparin .
Once the reaction was complete , corn trypsin inhibitor was used to inactive factor xiia , the enzyme generated by exposure of plasma to negatively charged surfaces , which had activated the factor xi .
Recent findings : patient studies , genetically altered mouse models , and plasma assays analyzed functions of the factor xii-driven contact activation system for coagulation and inflammation .
These data indicate that factor xi would not be autoactivated in a plasma environment , and thrombin would , therefore , be unlikely to potentiate the activation .
It is concluded that surface-immobilized heparin , unlike heparin in solution , effectively inhibits the initial contact activation enzymes by an antithrombin-mediated mechanism , thereby suppressing the triggering of the intrinsic plasma coagulation pathway .
A quantitative assay for total plasminogen activator plus proactivator in plasma showed that the amount in fletcher trait patients is about half of normal ( normal = +/- 100 blood activator units [bau] /ml ) .
Coagulation activation markers , such as prothrombin activation fragment 1+2 and thrombin-anti-thrombin complexes , are elevated in diabetes .
Concentrations of d-dimer , alpha 2-antiplasmin complex , and plasminogen activator inhibitor-1 also increased significantly during bypass in both groups .
Plasma kallikrein-mediated activation of the renin-angiotensin system does not require prior acidification of prorenin .
Complications include coagulation disorders ( bleeding diathesis , hyperfibrinolysis ) from platelet defects and plasmin activation , as well as pulmonary dysfunction from neutrophil sequestration and degranulation .
The levels of c1q and c3 were also decreased ( p less than 005 ) indicating an activation of the complement .
Thus the "physiologic , negatively charged surface" for contact system activation is really the assembly of these proteins on cell membranes and activation by membrane-associated enzymes .
This modulation was mediated by zn2+ and did not require an activating surface .
Zinc-dependent activation of the plasma kinin-forming cascade by aggregated beta amyloid protein .
All modifications reduced c3 activation compared with controls , but the greatest reduction was achieved with polyethylene oxide attachment or glycosylation .
Furthermore , anophensin interacts with both the n-terminus of fxii and domain d5 of hk , which are the binding domains for biological activating surfaces .
The quenching did not involve , quantitatively or qualitatively , the extrinsic ( tissue-type ) plasminogen activator activity varying between 1 and 146 bau/ml in baseline plasma and in plasma obtained after stimulation by venous occlusion , exercise , or ddavp administration .
Thrombin and factor xa were then directly tested for their ability to activate factor xi .
In addition to its action in intiating blood clotting through the intrinsic pathway , hageman factor can influence kinin generation , fibrinolysis , and activation of complement .
Although it appears marginally capable of activating hageman factor , it rapidly cleaves and inactivates the activated form so that the net effect is a loss of activatable hageman factor .
Heparin in a concentration of 7 units/ml. of plasma does not inhibit contact activation by glass .
In_vitro leukocyte chemotaxis ( boyden chamber technique ) in response to normal or patient's own serum activated with zymosan was normal .
In group a ( vs group b ) , the kallikrein-factor xii system was significantly activated ( 3 h after start of therapy ) : .
The intrinsic plasminogen activator activity ( dextran sulphate precipitated euglobulin ) was significantly increased in the hormone group and the cyclic pattern differed from that of the normal group .
Levels of activated fxii in survivors of myocardial infarction--association with circulating risk factors and extent of coronary artery disease .
Activation of hageman factor by adsorption to quartz surfaces ( in an aqueous environment ) also produced changes similar to those in the ellagic acid-activated hageman factor , including the negative ellipticity in the tyrosine region .
Changes in the structure of hageman factor accompanying activation have been examined in this study by circular dichroism spectroscopy .
To elucidate the mechanism by which activation of the contact system of blood coagulation leads to expression of fibrinolytic activity , we have determined the molecular characteristics of the plasminogen activators present in dextran sulfate-treated euglobulin fractions by electrophoretic-zymographic analysis and specific immunoadsorption .
Most of these anionic polyesters are able to activate both ppk and fibrinolysis , dextran sulphate ( 500,000 mw ) being the most active .
Kinetic analysis of a simplified scheme of autocatalytic zymogen activation .
Prekallikrein activator and kallikrein in acetone - and kaolin-activated rat plasma .
Activation of factor xii-dependent pathways in human plasma by hematin and protoporphyrin .
The presence of hageman factor abnormality trait can be clinically suspected in a patient with a prolonged activated partial thromboplastin time ( aptt ) , normal prothrombin time ( pt ) , normal bleeding time , and no clinical history of bleeding .
In the chromogenic substrate assay corn hageman factor inhibitor ( chfi ) inhibited the activation of s-2251 cleaving enzyme by gagps , pentosan polysulfate , polyanethol sulfate , heparin , and ribonucleic acid near completely .
We undertook the present study to investigate the relation of this activation to clinical symptoms , and the molecular pathways involved .
In this study , we investigated two different widely used leukocyte removal filters , pall pxl8k (a) and asahi pls-5a (b) , to test whether clinically significant contact activation occurred during leukodepletion of platelet-rich plasma ( prp ) .
[successes and failures of the activated partial thromboplastin time in the preoperative evaluation]
Prekallikrein is fully activated under these conditions and the activity remains stable for at least 30 hr .
In addition to the n-terminal domain , the growth factor and kringle domains and , to a lesser extent , the polyproline region also interact with negatively charged surfaces and presumably thus contribute to activation .
Plasminogen activator inhibitor-1 4g/5g polymorphism ( or 1.65 , 95% confidence interval [ci] 0.92-2.95 ) and increased plasminogen activator inhibitor activity were not significantly associated with recurrent miscarriage , although the latter showed profound heterogeneity across studies .
However , a physiological cofactor for thrombin activation of factor xi has not been identified .
The extrinsic coagulation pathway was dominantly activated , whereas the intrinsic coagulation pathway , including plasma kallikrein-kinin system , played less important role in the etx-induced consumption coagulopathy in rat .
These findings suggest that an endothelial binding protein mediates the assembly of critical components of the kinin-generating pathway on the surface of endothelial cells , thereby linking the early events of kinin formation and complement activation .
These findings could be clinically important , since there is evidence that the contact system is activated in ad brain .
Proteins of the plasma kinin-forming cascade bind to endothelial cells and activation of the cascade can be initiated along the surface .
Pk deficiency was suspected in view of a severely prolonged activated partial thromboplastin time ( aptt ) that nearly normalized following prolonged preincubation ( 10 min ) of patient plasma with kaolin-inosithin reagent .
Our recent investigations have postulated a human umbilical vein endothelial cell ( huvec ) -associated prekallikrein activator ( pka ) .
Plasminogen activators ( pa ) in the euglobulin fraction of dextran sulfate activated plasma ( ds-ef ) were assayed on fibrin plates .
Little data is available regarding the activated form of factor xiia ( fxiia ) in survivors of myocardial infarction. 292 caucasian patients characterised for extent of coronary atheroma by angiography and for a past history of myocardial infarction and 77 healthy controls were included in the study .
Three of the monoclonal antibodies ( 13g11 , 13h11 , and 6a6 ) were able to inhibit the activation of pk to kallikrein in both a plasma system and a purified system .
Purified factor ix(a) activated partially purified factor vii and had no additional indirect activating effect in the presence of plasma .
Activations of contact factors were not parallely occurred with the marked consumption of fxii .
An assumption was made on the mediated influence of the product of blood coagulation contact phase on neutrophils through the activation of intercommunicated blood plasma enzyme systems .
Thus , the plasma level of activated fxii ( xiia ) might represent vascular lesions or be a marker of abnormal lipid metabolism .
The clinical circumstances of the case , with severe hemorrhage refractory to plasma infusion but readily responsive to an alternate clot-promoting agent , suggest that a defect of intrinsic system activation was critical , supporting the inference that factor xi does participate in normal hemostasis .
The activation of these factors is self-amplified and triggers both expression and release of numerous mediators by endothelial cells and leukocytes .
Slight to extensive prolongation of the activated partial thromboplastin time was seen in the affected persons .
Zinc-dependent activation of the prekallikrein-hk complex on endothelial cells was inhibited upon the addition of polyclonal antibody to hsp90 in a dose-dependent manner .
These findings make it apparent that lowered hmw-kininogen levels compensate the lack of c1 inh , thus preventing an enhanced activation of the intrinsic clotting and the fibrinolytic systems .
After activation of the immobilized scu-pa for a certain period of time the activity of the generated amount of immuno-immobilized two-chain u-pa was determined with plasminogen and the chromogenic substrate s-2251 .
We therefore evaluated the quality of pcs prepared by leucocyte depletion of whole blood ( terumo wbsp , n = 10 ) or a buffy coat pool ( pall autostop , n = 10 ) , and stored for 7 days in plasma by assessing platelet parameters and markers of platelet activation .
Cholera toxin ( 1 microgram/ml ) and forskolin ( 100 microm ) , however , were much stronger activators of the adenylate cyclase system .
The activation of pro-uk by ppa-pretreated platelets was dose-dependent and inhibited by soybean trypsin inhibitor but not by bdellin , a specific inhibitor of plasmin , nor by the corn inhibitor of factor xiia .
Normal plasma activation was inhibitable by antibody to gc1qr and cytokeratin 1. thus , gc1qr and cytokeratin 1 , represent potential initiating surfaces for activation of the plasma kinin-forming cascade and may do so as a result of their expression along cell surfaces .
Inhibition was presumably related to neutralization of the negative charge of activators of hageman factor .
Activation was induced neither upon incubation with mab f3 , nor with that of control mabs.
However , kallikrein-cleaved abnormal f xii was not able to cleave factor xi and plasma prekallikrein , in contrast to activated normal f xii .
These data suggest that all patients were exposed to endotoxin and that high levels of anti-endotoxin antibodies may contribute to the prevention of endotoxin-induced contact activation , neutrophil degranulation and gut mucosal hypoperfusion occurring during major surgery and thus reduce the likelihood of the development of post-operative mof .
The platelet activation by cellulose was assessed by measuring the released serotonin .
This was not a non-specific effect since the reverse occurred with tissue plasminogen activator .
Gamma irradiation of leukoreduced ffps with 30 gy results in a significant but very weak activation of the coagulation and fibrinolytic system in ffps .
In addition , thrombin converts protein c to activated protein c. activated protein c functions as a negative regulator in the coagulation process by degrading factor viiia and factor va .
In_vivo , prevention of contact system activation beside the reduction of kallikrein generation , can also decrease the activation of complement system and the release of interleukin-6 , both factors being considered to play an important role in the inflammatory reactions in ad brain .
Our data suggest that the activation of a contact system is required to produce clinical symptoms .
The 30 000 fragment ( residues 307-506 ) of fva heavy chain produced by activated protein c appeared as early as at 90 seconds and increased with time .
Activation of the contact system by dextran sulphate , as reflected by the cleavage of hk on a western blot , was inhibited when the patient igg was added to pooled normal plasma .
Diluted cephotestr was used as activator and after 10 min activation time chromogenic substrate h-d-pro-phe-arg-pna was added .
Our results show that cs activation and both fxiia and kk produce reductions in clotting time and enhanced fibrinolysis in ukifteg .
Most biologic surfaces that activate fxii become expressed in disease states .
Activation of the coagulation cascade in c1-inhibitor deficiencies .
The observed spontaneous activation suggests that when fully activated , the c1s present in 1 ml of human serum will hydrolyse 1-2 mumol of atee/minute .
All the solutions studied did not affect the purified preparations of prekallikrein , but some of them activated partially purified preparations of hageman factor .
(2) serine proteases ( factor xa , thrombin , plasmin and trypsin ) activated prekallikrein in the plasma and the purified prekallikrein .
Whether trypsin serves to activate pta in_vivo is not yet clear .
In fact , when hf was added to kaolin or glass that had been incubated with hmwk and then washed , the inhibitory effect persisted , indicating hmwk that was bound to the surface blocked activation of hf .
Two proteases , chymotrypsin-like ( chy ) and trypsin-like ( try ) proteases , were activated in purified rat mast cells after degranulation with compound 48/80 .
The contribution of various enzymes in the activation of factor vii , determined from the increase in factor vii coagulant activity ( viic ) , was investigated following the exposure of citrated plasma to low temperature .
Prekallikrein activator ( hageman factor fragment ) in human plasma fractions .
We examined markers of thrombin generation and activity in patients enrolled in a randomized , placebo-controlled , dose escalating trial of the platelet glycoprotein iib-iiia inhibitor eptifibatide ( integrilintrade mark ) administered concomitantly with tissue plasminogen activator for the treatment of myocardial infarction .
Preincubation of mab 13g11 with prekallikrein ( added to prekallikrein-deficient plasma ) or with normal plasma inhibited surface activation of prekallikrein 60% to 80% , as judged by amidolytic and coagulant assays .
Activation of coagulation , fibrinolysis , and the vascular endothelium occurs after heart surgery with cardiopulmonary bypass ( cpb ) , but the effects of eliminating cpb in patients undergoing coronary artery bypass grafting ( cabg ) are unknown .
Based on the amino acid sequence , we have molecularly cloned the cdna for human hgf activator .
Contact activation was assessed by measuring fxiia , kallikrein , and fxia in complex with their major inhibitor , c1 inhibitor , and fxia was also determined as part of a complex with alpha(1) -antitrypsin .
Fibronectin ( fn ) and plasminogen activator inhibitor-1 ( pai-1 ) were detected by elisa method .
Kallikrein also activated factor vii in normal , factor xii- , and factor ix-deficient plasmas .
We developed a specific and sensitive assay for activated tafi ( tafia ) and studied its factor xi-dependent generation during clot formation .
To monitor contact activation in patients with sepsis , we developed highly sensitive radioimmunoassays ( rias ) for factor xiia-cl(-) -inhibitor ( cl(-) -inh ) and kallikrein-cl(-) -inh complexes using a monoclonal antibody ( moab kok 12 ) that binds to a neodeterminant exposed on both complexed and cleaved cl(-) -inh .
We concluded that clinical response to intravenous endotoxin in healthy human volunteers is associated with activation of the kallikrein-kinin systems .
Asp produced vl activity from human plasma apparently through kallikrein/kinin system activation , suggesting that asp can generate kinin in humans .
Activation of prekallikrein appears to occur via the active form of hageman factor .
These results suggest that transdermal estradiol reduces thrombophilic activation in men with advanced prostate cancer , and protects against the risk of thrombosis .
One possibility is extrinsic activation via tissue thromboplastin from injured leukocytes .
Plasma kallikrein/kinin system : a revised hypothesis for its activation and its physiologic contributions .
Blood coagulation may be activated by the extrinsic or intrinsic pathways .
Hence , the loss of long-term stability of the polyamino acid-coated alginate microcapsules is associated with activation of the complement system , degradation of the polyamino acid coating , and destabilization of the alginate core matrix , probably through loss of calcium-mediated ionic cross-linking of the guluronic acid polymers in the alginate .
Conclusions : all parameters indicative of activation of the bradykinin-forming cascade are activated in hereditary angioedema plasma versus normal plasma .
Lps infusion affected neither the formation and activation of monocyte-platelet aggregates nor plasma levels of scd40 and scd40l .
Zinc-dependent binding of plasma proteins to gc1qr , cytokeratin 1 , and perhaps u-par is requisite for activation to take place .
In this report , we describe current knowledge about how the proteins of the plasma kallikrein/kinin system interact with and become activated on cell membranes .
Glycosaminoglycans proved to be an initiating surface for starting contact activation and could explain kinin generation present in allergic reactions .
Fibrinolysis increased significantly during cycles 3 and 6 ( from 77% to 100% and 113% , respectively , p < 001 ) and showed a further increase after dextran sulphate activation ( from 134% to 158% and 167% , respectively , p < 001 ) .
The two heparin surfaces , however , differed markedly with regard to activation of the adsorbed fxii .
We now present evidence that fxii can undergo activation in the presence of phosphate ions ( p(i) ) and certain divalent metal ions .
Activated coagulation seems to be present in borderline hypertension before the appearance of clinical signs of vascular lesions .
Two types of activation mechanisms , contact activation on a negatively charged surface and a cascade activation by exogenous proteases are known .
It was found that immediately after rhuifn-gamma treatment , tissue plasminogen activator activity and antigen levels were not significantly decreased in volunteers .
Activation of the cascade using purified proteins or upon addition of abeta to plasma requires aggregation of a ( beta ) and the reactions are zinc-dependent .
It is not expected that heparin anticoagulant therapy will contribute to activation of the contact system .
Factor x , but not factor ix , was activated ( as measured by their activation peptides ) , and this activation correlated with f1 + 2 and thrombin-antithrombin complexes , suggesting that the tissue-factor/factor-viia pathway is the trigger for thrombin formation .
10-1 inhibited the activation of factor ix in coagulant assay for f.xia by mannhalter .
We believe that the "missing pathway" for factor xi activation remains an enigma that warrants further investigation .
To investigate the role of these two pathways in factor ix activation in humans , we have developed a sensitive procedure for quantifying the peptide that is liberated with the generation of factor ixa .
The target mentioned above may either be an inhibition of fxii activation or an inhibition of its proteolytic activity .
The reduction , however , of fibrinogen , plasminogen activator inhibitor-1 , and thrombomodulin was significantly greater in the irbesartan than in the atenolol group .
Pretreatment with clopidogrel did not result in a pronounced inhibition of the platelet and coagulation system activation in patients on aspirin undergoing elective coronary stent implantation .
Clotting tests based upon the activated partial thromboplastin time are disturbed by heparin .
At ph 5.2 , tissue-type plasminogen activator production was far lower than at higher ph values , and production of the plasminogen activator inhibitor showed a glucose concentration-dependent increase .
This inhibitor did not affect factor xi activation or the activity of preformed factor xia .
P(i) and zn ( ii ) ions promoted activation of fxii alone ( but not prekallikrein ) and the kinetics of this reaction suggested autoactivation .
Possible mechanisms of the activation are discussed .
However , platelet counts , activated partial thromboplastin times ( aptt ) , thrombin times , ethanol gelation tests , and antithrombin activity remained within the normal range .
These data suggest that activation of the contact system modulates directly or indirectly various mediator systems involved in the inflammatory response during severe sepsis in nonhuman primates .
The immediate consequence of plasma prekallikrein activation is the cleavage of high molecular weight kininogen ( hk ) with liberation of bradykinin .
Initiation of coagulation of recalcified prp in contact with the reconstituted collagen surface is caused by the activation of platelets .
The activation of platelets leads to a variety of morphological and biochemical alterations , culminating in their aggregation and in the selective release from storage organelles of different substances , among them those mentioned above .
Evidence of coagulation cascade activation in patients with active and recently active ibd suggests an increased risk of thrombogenesis during active disease that extends for a period of time after commencement of medications to induce remission in their disease process .
In spite of the anticoagulant activity of heparin platelet deposition and contact activation of coagulation occurs during dialysis .
The bacteriostat neomycin sulphate did not affect the course of cryoactivation , but did block the dextran sulphate - and kaolin-induced activation of prekallikrein and fxii respectively , and was therefore omitted .
Cells were washed once in serum-free media and then cultured for an additional 48 hours with 0 to 5000 ng/ml of the platelet activating factor in media containing either 0.25% bovine serum albumin or 1% fetal bovine serum .
Activation of hageman factor by collagen .
Background : factor xii-dependent bradykinin formation is thought to be responsible for the swelling associated with the various forms of c1 inhibitor deficiency , and complement activation is augmented during attacks of swelling .
In contrast , the other antibody ( winston-salem ) or its fab' inhibited the activation of fix by fxia in a concentration-dependent fashion but did not inhibit binding of fxi to hk .
From these results it is concluded that fxiia can contribute significantly to fibrinolysis as a plasminogen activator in the presence of a potentiating surface .
Kallikrein alone failed to activate partially purified factor vii but did so when purified factor ix was added .
Activated partial thromboplastin time ( aptt ) was examined in brown norway ( b/n ) katholiek rat , which was previously reported as high molecular weight kininogen deficient .
The results demonstrate that prehemorrhagic kallikrein-kinin system ( kks ) activation induced an increased severity of shock state with higher mortality .
In contrast , activated hageman factor retained full activity in the presence of schistosome extracts as tested both on an amidolytic synthetic substrate and a natural substrate , plasma thromboplastin antecedent ( factor xi ) .
Increased plasma levels of activated factor fxii ( fxiia ) are associated with increased risk of atherosclerosis and coronary heart disease .
We conclude that the interactions of the light chain of hk via hkh20 is of particular importance for activation of the bradykinin forming cascade in zinc-dependent or independent reactions and is true for all "surface" initiators tested thus far .
Furthermore , the rate of fxiia accumulation in whole-plasma and buffer solution is found to decrease with time in the continuous presence of activating surfaces , leading to a steady-state fxiia yield dependent on the initial fxii solution concentration for both hydrophilic and hydrophobic procoagulant particles suspended in either plasma , protein cocktail , or buffer .
Since thrombin induces a marked redistribution and release of tfpi from stimulated endothelial cells and platelets contain about 10% of tfpi activity that is secreted following activation it is possible that thrombin-induced release of tfpi by endothelium and platelets could account for the increased tfpi we found during hemodialysis .
The contact surface is rate-limiting for the activation of factor vii in the plasmas in both groups of subjects and can be supplemented by large multilamellar liposomal vesicles carrying the appropriate density of negative charge .
In the presence of plasma kallikrein , hmwk at moderate concentrations slightly accelerated the rate of activation of hf by activating agents other than ellagic acid .
Lack of clinically significant contact system activation during platelet concentrate filtration by leukocyte removal filters .
Surface binding of hageman factor enhanced its cleavage by plasmin , activated factor xi , and trypsin by 100-fold , 30-fold , and 5-fold , respectively .
The contact activation mechanism in human plasma : activation induced by dextran sulfate .
The study of molecular markers of coagulation and fibrinolysis have shown a distinct increased activation of coagulation ( f 1 + 2 , fpa ) and fibrinolysis ( pap ) , and an increased fibrin turn-over ( increased fdps ) ; platelet products are not found increased ( beta tg , pf-4 ) .
Our results indicate that activation of tafi in serum after clot formation can be quantitated and that it takes place in both factor xi-dependent and factor xi-independent mechanisms .
Activation of hemostasis after coronary artery bypass grafting with or without cardiopulmonary bypass .
Angiotensin ii ( ic ( 50 ) = 2 microm ) or bradykinin ( ic ( 50 ) = 100 microm ) , but not angiotensin ii- ( 1-7 ) or bradykinin ( 1-5 ) , and the prolyl oligopeptidase inhibitor fmoc-ala-pyr-cn ( ic ( 50 ) = 50 nm ) also blocked purified pka activation of pk .
The addition of microfilarial extracts to human plasma prolonged the activated partial thromboplastin time in a dose-dependent fashion but did not prolong the prothrombin , thrombin , or russell's viper venom times .
When prekallikrein was activated in plasma depleted of both c1 esterase-inhibitor and alpha 2-macroglobulin , 6% of prorenin was activated in 2 hours at 37 degrees c. after additional depletion of antithrombin iii , the activation increased to 47%. these results indicate that the contact activation system is capable of activating prorenin in plasma at physiologic ph and temperature when the three most important kallikrein inhibitors , c1 esterase-inhibitor , alpha 2-macroglobulin , and antithrombin iii , are absent .
In conclusion we found evidence of thrombin generation and possible endothelial damage together with increased neutrophil activation and adhesion molecule expression in the pulmonary vein during cpb which may play an important role in the development of post-cpb pulmonary injury .
The contact system , via the release of bradykinin and the activation of factor xi , has been postulated to be contributing to the observed hypotension and dic .
The preparation obtained from plasma of dextran-treated rats was significantly more potent than was the normal kallikrein preparation , both as regards the effect against hmrk , and as an activator of plasminogen .
This suggests that physiologic activation of factors xi and ix does not occur exclusively in series because deficiency of factors xii , xi , viii , and ix should then have similar hemostatic consequences .
Prophylaxis with dalteparin at doses used in this study did not reduce coagulation activation in high risk thrombophilic women during pregnancy .
Show that misfolded protein aggregates produced during systemic amyloidosis allow for plasma fxiia and prekallikrein activation and increased formation of kallikrein-c1 inhibitor complexes , without factor xia activation and coagulation ( see the related article beginning on page 3208 ) .
In the present studies , we report that the activation of purified human hf by sulfatides , ellagic acid , kaolin , or glass occurred in the absence of hmwk .
Since these factors are serine protease zymogens , the activation of these molecules usually results from the cleavage of a particular -arg-ile ( val ) - bond in either mechanism .
These complexes were probably formed by activation of urokinase-type plasminogen activator ( u-pa ) , and not tissue-type plasminogen activator ( t-pa ) , since sf levels of both u-pa antigen and u-pa-plasminogen activator inhibitor ( pai ) complexes were increased in 27 of the 42 patients .
Factor xi has been shown to be efficiently activated in_vitro by surface-bound factor xiia after factor xi is transported to the surface by its cofactor , high molecular weight kininogen ( hk ) .
These data indicate that hka ( active cofactor produced during contact activation by factor xiia or kallikrein ) is primarily responsible for displacing fibrinogen , and that hki ( inactive cofactor generated by factor xia ) cannot displace fibrinogen .
The organization and structure of the gene coding for hepatocyte growth factor activator ( hgfa ) have been determined by isolation of unique clones from a human genomic library .
Supra-additive cytotoxic effects of a combination of cytostatic drugs and antibody-induced complement activation on tumor cells in_vitro .
Recently , a novel serine protease responsible for this processing ( hgf activator ) has been purified from fetal bovine serum ( shimomura , t , ochiai , m , kondo , j , and morimoto , y ( 1992 ) cytotechnology 8 , 219-229 ) .
Using quantitative immunoassays , the time courses were evaluated for activation of prothrombin , factor (f) v , fxiii , fibrinogen ( fbg ) cleavage , and fva inactivation in bleeding-time blood collected at 30-second intervals from 12 healthy subjects both before and after aspirin ingestion .
Effect of heparin on the activation of factor xi by fibrin-bound thrombin .
Human plasma kallikrein was prepared by proteolytic activation of prekallikrein with beta-factor xiia ( mr = 28,000 ) .
Factor xii-induced mitogenesis is mediated via a distinct signal transduction pathway that activates a mitogen-activated protein kinase .
In the absence of plasma prekallikrein , maximal activation of plasma thromboplastin antecedent was slightly delayed in plasma , a delay not observed with similarly treated purified hageman factor .
In the first two cases without any anticoagulants , fibrinopeptide a ( fpa ) and thrombin-antithrombin iii complex ( tat ) increased markedly over the course of lvad treatment , suggesting the excessive activation of the coagulatory system .
Injection of ac also reversibly blocked the activation of prekallikrein ( pk ) normally obtained in plasma incubated with acetone .
As these decreases , already observed after 1 day treatment , were disproportional to that of albumin , a negative acute phase reactant , and correlated with signs of the vascular leak syndrome , we favor the explanation that they reflected activation rather than a decreased synthesis of the contact system proteins.
After exposure for 30 min to bacterial preparations ( 002-5 mg/ml ) at 0 c , lallikrein amidolytic activity was expressed as a percentage of the optimal activation of prekallikrein induced by dextran sulfate .
Our results suggest that tumor necrosis factor could play an important part in the early activation of the hemostatic mechanism in septicemia .
In patients with antiphospholipid antibodies or hypofibrinolysis , there is a non-inflammatory ongoing chronic elevation of markers of endothelial stimulation associated with coagulation activation .
However , the latter effect , although undoubtedly contributing to the formation of factor xiia at the surface , seems to be of less importance than the reciprocal activation mechanism .
The dissociation of complement serum and plasma was due to cold activation of the classical pathway of complement in_vitro since serum drawn from these patients at 37 degrees c lost hemolytic activity in 4 hours when transferred to a cold environment .
In plasma an intact factor xi-dependent feed back loop via the intrinsic pathway is necessary to generate sufficient thrombin for tafi activation .
Measurement of activated factor xi and alpha 1 antitrypsin complex developed by us is the only one measure for detecting contact phase hypercoagulation .
Antibody to cytokeratin 1 inhibited hk binding to endothelial cells by 30% , antibody to gclqr inhibited hk binding to endothelial cells by 72% , and a mixture of both inhibited binding by 86%. the binding and activation of the proteins of the kinin-forming cascade along the cell surface is zinc-dependent .
To investigate the effect of the peroxisome proliferator activated receptor-gamma ( ppar-gamma ) agonist troglitazone on tgf-beta(1) and fibronectin ( fn ) expression in human peritoneal mesothelial cells ( hpmcs ) .
During the first 40 min of ecc , these changes were paralleled by a significant rise in c3a concentration , suggesting complement activation as a main cause for pmn activation .
Thus , physiologic fxii expression on huvecs is secondary to hk binding and highly restricted in its ability to initiate prekallikrein or fxi activation .
Activated fxii relates to both extent of coronary atheroma and to a past history of myocardial infarction and clusters with features of insulin resistance .
Activation systems in contrast idiosyncrasy .
Here we report that activation of the contact system by salmonella leads to massive infiltration of red blood cells and fibrin deposition in the lungs of infected rats .
Further studies will be necessary to show if pk activation is altered or reduced in other congenital clotting abnormalities .
The absence of contact system activation was further supported by stable plasma levels of the individual factors of contact activation .
These results indicate that slight differences in the proportions and/or distribution of sulfated residues along the galactan chain may be critical for the interaction between proteases , inhibitors and activators of the coagulation system , resulting in a distinct pattern in anti - and procoagulant activities and in the antithrombotic action .
Fluctuations of the extrinsic ( tissue-type ) plasminogen activator ( t-pa ) activity parallelled those of the euglobulin activity .
Prothrombin time , expressed as international normalized ratio ( inr ) and activated partial thromboplastin time ( aptt ) , are standard methods of monitoring coumadin and heparin administration .
Fxii activation in neat-buffer solution was effectively instantaneous upon contact with either hydrophilic ( fully water-wettable clean glass ) or hydrophobic ( poorly water-wettable silanized glass ) procoagulant particles , with greater fxiia yield obtained by activation with hydrophobic procoagulants .
The present results support the previous observations , and indicate that acetone treatment of fresh human plasma ( benzamidine present ) results in the activation of plasma kallikrein in a functional state that requires kinin-free , but otherwise native hmrk as a cofactor for the activation of xii.
(i) the activation of factor xi by activated hageman factor ; ( ii ) the activation of prekallikrein by activated hageman factor ; and ( iii ) the activation of hageman factor by kallikrein .
The aim of the present investigation was to clarify whether immobilized heparin does , as previously suggested , prevent triggering of the plasma contact activation system .
We compared plasma markers of coagulation activation in_vivo and red blood cell ( rbc ) markers of procoagulant activity in 15 hb e/beta-thal patients who were not splenectomized ( ns ) , 15 who had been splenectomized (s) , and 15 normal controls ( nc ) .
Immunoblots of activated rhesus plasma showed prekallikrein , complexes of kallikrein with c1 inhibitor , alpha 2-macroglobulin and approximately 60-kda inhibitors ( viz antithrombin iii ) , and 45-kda fragments , like those in activated human plasma .
Here we report that a number of serine proteases can activate mmp-1 and cause capillary tube regression ; namely plasma kallikrein , trypsin , neutrophil elastase , cathepsin g , tryptase and chymase .
These results suggest that anophensin inhibits activation of the kallikrein-kinin system by interfering with the association of fxii and hk with biological activating surfaces , resulting in the inhibition of bradykinin release in a host animal during insect blood-feeding .
Glass-bound rfxii-u-like was able to activate prekallikrein in fxii-deficient plasma ( assessed by measuring the generation of kallikrein-c1-inhibitor complexes ) , but less efficiently than rfxii , rfxii-u-like and rfxii-lpc exhibited coagulant activity , but this activity was significantly lower than that of rfxii .
Mc-heppg gags therefore represent a physiologic macromolecule with activity comparable to non-physiological surfaces in a purified system and with the capability to induce activation of the contact system in diluted plasma .
The recent finding that hypotensive reactions to blood products can be attributed to the presence of a prekallikrein activator in the products , prompted us to measure the distribution of this substance among plasma fractions produced by the cold ethanol method .
Both mdr-1 pgp and mdr-1 mrna were significantly increased in cells cultured in the presence of cyclosporin a ( csa ) , 1,25 ( oh ) (2) d(3) , platelet activating factor , dexamethasone ( dex ) , or aldosterone .
Activation of the contact system and inflammation after thrombolytic therapy in patients with acute myocardial infarction .
Incubation of aggregated abeta with diluted human plasma also led to prekallikrein activation and hk cleavage .
These findings suggest that the development of a collection tube that prevents contact activation also would inhibit adequately the cold-promoted activation of the pt and factor vii .
We evaluated the effects of em on activation of several transcription factors , including nuclear factor-kappab ( nf-kappab ) and activator protein-1 ( ap-1 ) in human bronchial epithelial cell line bet-1a , which are known to regulate the expression of many proinflammatory cytokines and chemokines such as interleukin-8 ( il-8 ) .
Solution yield of fxiia arising from fxii contact with hydrophilic activating particles ( fully water-wettable glass ) suspended in a protein cocktail is shown to be significantly greater than that obtained under corresponding activation conditions in buffer solutions containing only fxii .
Effect of factor xa inhibitors on thrombin formation and complement and neutrophil activation during in_vitro extracorporeal circulation .
Contrary to low-fat meals , high-fat meals are known to cause postprandial factor vii ( fvii ) activation , but the mechanism is unknown .
In earlier studies using crude systems , platelet factor 4 inhibited activation of hageman factor by dextran sulfate or cerebrosides , but not activation of hageman factor by kaolin or ellagic acid .
Activation of humoral and cellular participants in inflammation enhances the risk of postoperative bleeding and multiple organ damage in cardiopulmonary bypass ( cpb ) .
This assay appeared to be discriminative even for materials that are considered mild activators of the contact system and can therefore be used as a standard method to qualify biomaterials.
It has been suggested that a factor xii-plasma prekallikrein dependent pathway might play an important role in the activation of inactive renin .
Here activation of glu - and lys-plasminogen by factor xiia in the absence of prekallikrein/kallikrein and high mr kininogen was studied in a purified system by the generation of amidolytic activity towards pyroglu-phe-lys-pna ( s-2403 ) , a chromogenic substrate of plasmin .
We specifically examined the roles of factors xii , xi , and ix in activation of factor vii during alimentary lipemia in_vivo in humans and addressed the issue of whether generation of activated factor vii ( viia ) is accompanied by increased thrombin production .
(3) preactivation of normal plasma by a contact activator such as celite eliminates essentially all inhibitory activity .
The oscs found in contaminated lots of unfractionated heparin , as well as a synthetically generated oscs reference standard , directly activated the kinin-kallikrein pathway in human plasma , which can lead to the generation of bradykinin , a potent vasoactive mediator .
So , the absence of kallikrein in the deficient plasma cannot fully account for the reduction in activator activity .
However , activation of hk was observed in all four patients with angioedema , the two patients with shock but no angioedema , as well as in 1 of the remaining 6 patients with anaphylactic symptoms other than angioedema or shock .
Pgh also inhibited preparations of activated pta ( factor xi ) and thrombin , and , when incubated with plasma , reduced the titer of coagulable fibrinogen , pta christmas factor ( factor ix ) , antihemophilic factor ( factor viii ) , factor vii , stuart factor ( factor x ) , proaccelerin ( factor v ) and prothrombin ( factor ii ) , and to a lesser degres , hf .
In the absence of lps , the initial activation product of hf , hfa , which contains the serine protease enzyme activity and the surface-binding domains of the protein , induced il-1 beta protein and mrna .
Scu-pa activators were detected in an assay system in which the substrate scu-pa , in physiological concentration ( 50 pm ) , was immuno-immobilized .
Activation of f. xii-2 took place on incubation with porcine plasma kallikrein , and the activation rate was increased only in the presence of negatively charged surfaces , such as sulfatide .
The sulfatide-mediated activation of reaction 1 was not inhibited by fragment 1.2 ( his-rich fragment ) , which is released from hmw kininogen by the action of kallikrein , and is known to be a potent inhibitor of the kaolin-dependent activation .
Despite lower plasma concentrations of heparin , aprotinin-treated patients had significantly lower concentrations of the markers of coagulation activation ( thrombin-antithrombin iii complex , fibrin monomers , and antiplasmin-plasmin complex ) .
We have shown that thrombin activity increases in plasma and whole blood incubated with plasminogen activators and appears to be plasmin mediated and dependent on activity of the factor viiia/ixa complex .
Activation of the zymogen of hepatocyte growth factor activator by thrombin .
Species differences in amino acid sequences of hageman factor and prekallikrein at region around scissile bond in activation .
Probably this is the reason why the beta-form activated hageman factor ( the proteinase moiety ) is not liberated in the activation of the bovine molecule with trypsin or plasma kallikrein .
Both forms are cleaved by activated hageman factor , they appear to share antigenic determinants , they are not interconvertible upon incubation with activated hageman factor or kallikrein , and the ratio of kinin-generating , and plasminogen-activating activities of the preparations are independent of the relative proportion of each band .
Inhibition of the coagulation cascade was assayed by protein c , protein s and activated protein c resistance ( apc-r ) .
These studies demonstrate that factor xiia , at concentrations potentially obtainable in plasma in disease states , can activate neutrophils , and thus may participate in the inflammatory response .
Recent studies have described genetic mutations that affect the risk of thrombosis as a result of abnormal levels of such hemostatic parameters as protein c , protein s , and the activated protein c resistance ratio .
Alteration of factor vii activity by activated fletcher factor ( a plasma kallikrein ) :a potential link between the intrinsic and extrinsic blood-clotting systems .
Blood drainage , allogeneic blood transfusions , and intraoperative activated coagulation time were recorded .
The activation of the kks influences the permeability of the endothelium by liberating bradykinin ( bk ) from hk .
Activation of coagulation during treatment with haemodialysis .
Although surface-activated contact activation occurs in_vivo in the case of tissue destruction or a developing thrombus , the physiologic basis for the activation and function of this system has not been delineated .
Compared on a molar basis , however , plasmin was found to be almost 1,000 times more effective than kallikrein , and we conclude , therefore , that in_vivo plasmin is the primary activator of scu-pa and the role of the contact system is of secondary importance .
Elevated activated fxii ( fxiia ) levels have been previously associated with chd .
Thus , c1q inhibits activation of hf in_vitro in clot-promoting and amidolytic assays and suggests a regulatory mechanism for the inhibition of coagulation .
We hypothesize , that the observed presence of gender differences in the plasmin - and thrombin activation system in pph leading to an antifibrinolytic/prothrombotic state might , in part , explain the female predominant incidence of this disease .
Activation of the coagulation cascade in severe falciparum malaria through the intrinsic pathway .
The depression of pre-kallikrein indicates that the dic is probably triggered by activation of the intrinsic coagulation pathway .
To study the postprandial fvii activation in detail , 18 young men consumed in randomized order high-fat or low-fat test meals .
The role of limited proteolysis in the activation of prekallikrein induced by dextran sulfate was studied by adding 125i-prekallikrein to plasma .
The data demonstrate that aggregated a ( beta ) can bind and activate proenzymes of the plasma kinin-forming cascade to release bradykinin and these reactions are dependent on zinc ion .
This report examined the effect of various doses of a synthetic platelet activating factor on the production of progesterone by porcine granulosa cells in culture .
Some , but not all , studies have shown that this activation may be brought about by collagen .
Minimal activation of tafi was detected in factor ii deficient plasma when clotting was initiated by 20 nm thrombin .
Hageman factor substrates .human plasma prekallikrein : mechanism of activation by hageman factor and participation in hageman factor-dependent fibrinolysis .
In these studies , we show that incubation of serum with microtiter plate bound gc1qr results in complement activation , as evidenced by the binding and activation of c1 and generation of c4d .
Future studies will investigate the quantitative impact of the various activated pathways ( cause or reaction ) and the effects of interventions on these pathomechanisms in patients with acute coronary syndromes .
A low or transient complement activation via the classical pathway was indicated on ethanol washed cr , since deposition of secondary antibodies to complement factor iq ( ciq ) was observed only after short incubation times in serum .
Fibrinogen , the preferred substrate for thrombin in plasma , virtually prevented autoactivation of factor xi as well as the thrombin-mediated activation of factor xi , while having no effect on factor xiia-catalyzed activation .
The presence of albumin greatly enhanced activation of the amidolytic properties of purified hf by ea , even when albumin had been lipid-extracted or treated with dfp or sbti ; albumin also increased activation of hf by sulfatides .
Activation of hemostasis during cardiopulmonary bypass and pediatric aprotinin dosage .
These results suggest that the intrinsic pathway of the clotting cascade is activated in severe malaria .
Furthermore , treatment of platelets with plasma pk activator ( ppa ) , consisting essentially of factor xiia , induced activation of pro-uk and of chromogenic substrate for kallikrein ( s-2302 ) .
The staining in normal skin was confined to the highly proliferative activated follicular keratinocytes , whereas most cholesteatomas showed a staining of all cell layers of the epithelium .
The activation rate of rfxii-triangle up19 by kallikrein in the absence of dextran sulfate was about four times higher than that of full-length fxii and was increased in the presence of dextran sulfate .
Thrombin activatable fibrinolysis inhibitor ( tafi ) also known as plasma procarboxypeptidase b is activated by relatively high concentrations of thrombin in a reaction stimulated by thrombomodulin .
Furthermore , activation of factor xi in human disease , especially atherosclerotic disease , measured by newly developed immunologic assays , is discussed .
Factor ix is activated in_vivo by the tissue factor mechanism .
Patients had higher willebrand factor antigen ( vwf ) , tissue-type plasminogen activator antigen ( t-pa ) , plasminogen activator inhibitor activity ( pai ) and d-dimers ( d-di ) than the reference women .
Despite systemic heparinization , extracorporeal circulation will induce activation of blood coagulation .
Nonsurvivors of sepsis were distinguished mainly by high plasminogen activator inhibitor values ; this suggests an impaired functional fibrinolysis in fatal sepsis , with possible therapeutic implications .
Preliminary laboratory findings revealed anemia , hypoproteinemia , thrombocytopenia , and prolongation of the activated partial thromboplastin time .
(1) at the early stage of the activation reaction , kallikrein activity was first generated after short lag time , and then factor xiia activity was generated with a sigmoidal curve .
Despite absence of hageman factor , evidence for activation of complement by the classic pathway and thromboembolic phenomenon was observed .
Although surface-activated contact activation occurs in_vivo when various negatively charged surfaces become exposed , including a developing platelet thrombus , a physiologic , non-injury mechanism for activation , regulation , and function of this system has been elusive .
Continuous venovenous haemofiltration using polyacrylonitrile filters does not activate contact system and intrinsic coagulation pathways .
In the present study , a kinetic analysis of the entire progress curve for the autocatalytic zymogen activation reactions is presented .
Initiation of the plasma contact system has been shown to play a significant role in the fibrinolysis , activating both pro-urokinase and plasminogen .
We conclude that moderate surgical trauma with blood losses greater than 300 ml can activate thrombin generation and fibrinolysis during operation .
On the other hand , the dsc column generates bradykinin by activation of the initial contact phase of the intrinsic coagulation pathway .
Kallikrein-kinin system activation in streptococcal toxic shock syndrome .
Since thermal denaturation is associated with transformation of collagen structure from triple helical to random coil form , it is suggested that the native form of collagen is essential for the ability to activate hageman factor .
In conclusion , pk was shown to be tightly associated with platelets where it can be activated by factor xiia during clotting .
Methods : we compared spontaneous and kaolin-induced activation of normal plasma with the plasma of patients with hereditary angioedema .
Activated fxii ( alphafxiia ) brings about reciprocal activation of fxii and kallikrein that by further hydrolysis produces the free catalytic domain ( betafxiia ; 28 kda ) .
In this study we have used alanine scanning mutagenesis to identify residues on rantes that specifically interact with its receptors ccr1 , ccr3 , and ccr5 for binding and activation .
We assessed levels of coagulation activation markers and apl during normal pregnancy and in women with the antiphospholipid syndrome ( aps ) .
In this study , we sought to determine if similar increases in activated partial thromboplastin time or activated clotting time due to heparin or bivalirudin would reflect the same degree of inhibition of thrombin formation .
The combined results indicate that ti-surfaces initially activate complement through the classical pathway .
However , filtration through a negatively charged filter resulted in a decrease in the amounts of prekallikrein and an increase in the amount of bradykinin generated , which indicated the activation of the contact system .
Thrombin activity is enhanced , and contact-system activation via plasminemia might be possible .
However , platelet activation assessed by beta-tg was similar in both groups of patients .
Tissue-type plasminogen activator ( t-pa ) activity increased by 260% and 167% ; t-pa antigen decreased by 12% and 18% , and t-pa inhibitor activity decreased by 31% and 32% , respectively .
A time course for the generation of activated fxii using purified fxii solution at physiologic concentrations on two similar negatively charged polymers was performed .
It was concluded that kinin formation in the nephrotic syndrome was not due to the activation of intrinsic coagulation system but due to release of kinin from low molecular weight kininogen .
Activity quenching in various plasmas ( including plasma adsorbed by agarose-bound auk ) demonstrated the involvement of a discrete activator activity of 40 to 50 bau/ml with little variation among individuals ( 43 +/- 6 ( sd ) bau/ml , n = 13 ) .
Thus , activation of hageman factor by negatively charged agents was not necessarily accompanied by molecular scission .
Activation of plasminogen through surface-mediated reactions is well recognized .
Determination of prothrombin activation fragments in young patients with inflammatory bowel disease .
Therefore , a complete evaluation of all these properties of fxii and fxiia has to be considered when formulating a strategy for blocking fxii activation .
Two different incubation times for the activated partial thromboplastin time ( aptt ) :a new criterion for diagnosis of lupus anticoagulant .
The baseline celite activated clotting time ( act ) was greater than 1400 seconds and the thrombin time was 12.4 seconds ( control , 119 seconds ) .
Activation of the plasma kallikrein-kinin forming cascade takes place upon incubation with human umbilical vein endothelial cells .
In addition to 25% albumin and the fraction v rework fractions leading to it , only supernatant iii from the fraction ii + iii reworks was found to be free of the prekallikrein activator .
Gc1qr and soluble urokinase-like plasminogen activator receptor also inhibited biotin-hk binding to cytokeratin .
Activation of the coagulation system was shown by an increase in the fvii activity ratio ( 119 +/- 029 versus 131 +/- 034 ; p = 00000001 ) , fxiia ( 081 +/- 050 ng/ml versus 090 +/- 051 ng/ml ; p = 0006 ) , and f1+2 ( 119 +/- 020 nmol/l versus 124 +/- 020 nmol/l ; p = 0000005 ) after irradiation with 30 gy , whereas an increase of pap ( 162 +/- 115 ng/ml versus 202 +/- 120 ng/ml ; p = 00004 ) demonstrated activation of the fibrinolytic system .
Thrombin iii activation remained at the same level after a primary increase , but protein c activation was decreased .
Using heparan sulphate , which is present in the human vascular system , activation of about 1-2% of plasma fxi was observed , however , only after addition of very high amounts ( 500 nmol/l ) of human alpha-thrombin to fxii-deficient plasma ( at a 1 to 4 final dilution ) .
Release of endothelial cell heat shock protein 90 ( hsp90 ) or the enzyme prolylcarboxypeptidase leads to activation of the bradykinin-forming cascade by activating the prekallikrein-hk complex .
The mechanism of c4 activation was not dependent on c1q , because non-fibrillar betaa can still activate c4 in plasma genetically deficient in c1q. a c1q independent mechanism of complement classical pathway activation could be via the activation of contact/kinin system .
Inhibition of the cold activation of factor vii and the prothrombin time .
Furthermore , the synthetic peptide 3-19 , preincubated with factor xi , inhibited up to 30% activation of factor xi both in the purified system as well as in plasma .
A parallel decrease of factor (f) xii and a fibrinolytic inhibitor of plasminogen activation ( pa inhibitor ) was found in a series of 52 patients subjected to vascular surgery .
The mechanisms by which human high molecular weight kininogen ( hmkrk ) contributes to the surface-dependent activation of the hageman factor systems have been studied .
Activation of the contact system of coagulation does not contribute to the hemostatic imbalance in hypertriglyceridemia .
This antibody , purified from ascites fluid , reacted with hf to inhibit the activation of hf , purified or in normal pooled plasma , as measured by a coagulation assay .
The complex of activated factor xi with inhibitor prevented the cleavage and activation of factor ix .
Inhibition of ellagic acid-induced activation of hageman factor by both forms of amyloid precursor protein was enhanced by heparin .
The best overall surface , however , was the glucose-modified surface which was least activating considering all parameters of blood compatibility .
Our data indicate that in c1-inhibitor deficient patients there is increased generation of thrombin during attacks , with signs of activation of both the contact and tissue factor coagulation pathways .
Activation of platelets in the venous occlusion test .
Certoparin , dalteparin , and enoxaparin significantly inhibited coagulation activation marker formation in shed blood .
This was followed by an experimental study to determine whether streptococci or streptococcal products could activate the human contact system in_vitro .
In both assays gagps proved the most potent activator , while pentosan polysulfate exhibited 83% and 44% and heparin 32% and 14% of gagps fibrinolytic activity in the chromogenic substrate test and the fibrin plate assay , respectively .
These findings suggested a significant contribution of fxiia as a direct plasminogen activator .
Activation of the contact system by filtration of platelet concentrates with a negatively charged white cell-removal filter and measurement of venous blood bradykinin level in patients who received filtered platelets .
Further kallikrein formed on endothelial cell membranes is capable of cleaving its receptor and native substrate , high molecular weight kininogen , liberating bradykinin and terminating activation .
Intraglomerular coagulation , initiated by the local activation of contact coagulation factors , has been suggested as one possible factor causing glomerular injury in iga nephritis .
Tafi-deficient plasma activated with celite was noted to have a duration of clot lysis not different from samples activated with tf , but a significant difference in time to onset of lysis persisted .
The role and relative importance of each of the naturally occurring plasma protease inhibitors ( c1-inhibitor , alpha-2-macroglobulin , alpha-1-antitrypsin , antithrombin iii , and alpha-1-antiplasmin ) will be assessed as they relate to the dampening of contact phase activation .
Systemic and translesional activation of coagulation , fibrinolytic , and inhibitory systems in candidates for coronary angioplasty : basal state and effect of successful dilation .
Stoichiometric rather than catalytic amounts of hmrk gave optimal activation of factor xi .
In conclusion , we did not detect an effect on activation markers of the contact coagulation system in hypertriglyceridemic patients after triglyceride-lowering therapy .
Although the ensuing activation of platelets is well established , their contribution for thrombosis and tissue damage has not formally been proved .
Pbmc also inhibited hf activation by glass or sulfatides .
Although minimal activation was seen without adp , the fraction of platelets expressing p-selectin in response to adp was greatest in blood anticoagulated with citrate compared with cti and all other anticoagulants .
Treatment of lung fibroblasts with habp lead to a rapid activation of signalling pathways , including the mitogen-activated protein kinase ( mapk ) pathway with c-raf , mek and erk1/2 .
The plasmas of six patients with prolonged activated partial thromboplastin times were studied in detail .
Epinephrine-activated platelets stimulating thrombin formation interact with endothelial cells activated by angiotensin ii to cause , first , smooth muscle cell proliferation , which is a histological hallmark of atherosclerosis , and , lastly , a symptomatic thrombotic occlusion-the stroke .
When the preparation was incubated with sulfatide , spontaneous activation was not observed on the condition that we used .
Prcp appears to be a huvec-associated pk activator .
Significant correlation was seen neither between activated partial thromboplastin time and f1.2 nor between activated partial thromboplastin time and prothrombin .
Plasmin-mediated activation of the contact system of coagulation appears to account , at least in part , for increases in procoagulant activity in patients treated with fibrinolytic agents .
Previously identified binding proteins include gc1qr , cytokeratin 1 , and the urokinase plasminogen activator receptor ; however , their relative contributions to binding are not yet clarified .
We found different activation efficiencies of these zymogens between human and guinea pig in both types of activation , and micro-heterogeneity of the sequence around the scissile bond among human , guinea pig and bovine hageman factors , or between human and guinea pig prekallikreins .
Thrombin activation and generation often occur with thrombolysis for acute myocardial infarction .
The activation of the contact phase of coagulation by physiologic surfaces in plasma : the effect of large negatively charged liposomal vesicles .
Heparin coating of an extracorporeal device may reduce blood activation .
As a step in elucidating the biological role of plasma kallikrein ( pk ) present in the follicular fluid of mammalian ovaries , we examined pig ovary fluid to determine its constituent activators and substrates .
These observations show a crucial role for c1-inh and alpha 2m in prorenin activation and explain , at least in part , why the ph of the acid-treatment step has to be less than 4 before irreversible activation of prorenin at neutral ph can occur .
Patients with hereditary angioedema lack c-1 inhibitor , a plasma alpha 2-glycoprotein that inhibits both the proteolytic action of c1 , the activated first component of the complement system , and the activity of components of the contact phase of coagulation : kallikrein , factor xia , and factor xiia .
Four antibodies had no effect directly on the amidolytic activity of activated f.xi ( fxia ) .
Whale plasma contained inhibitory activities against thrombin , activated stuart factor , activated pta , activated fletcher factor , and plasmin .
By analogy with studies in rat plasma this protease might be a plasminogen activator ( berstad & briseid 1982 ; johansen & briseid 1983 ) .
Detection of activation of the contact system of coagulation in_vitro and in_vivo : quantitation of activated hageman factor-c-1-inhibitor and kallikrein-c-1-inhibitor complexes by specific radioimmunoassays .
Accordingly , plasminogen activator inhibitor levels increased .
These observations suggest that zymogens of the contact system are activated during attacks of hereditary angioedema and that some of the clinical manifestations may be mediated through products of this pathway , such as kinins .
The activation reaction was ionic-strength dependent .
The matrix-bound rbetafxii was subjected to refolding with the glutathione redox system and activated by the in_vivo activator , kallikrein .
Inhibition of contact activation also modulated the fibrinolytic response , since the release of tissue-type plasminogen activator ( t-pa ) and the appearance of plasmin-alpha2-antiplasmin ( pap ) complexes into