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 ) is activated on contact with various biologic surfaces , including subendothelial tissues and lipoprotein particles .
Coagulation factor XII ( FXII ) activity , activated FXII , distribution of FXII C46T gene polymorphism and coronary risk .
Factor XII ( FXII ) and high molecular weight kininogen ( HK ) mutually block each others binding to the urokinase plasminogen activator receptor ( uPAR ) .
Hageman factor ( factor XII ) is activated by exposure to surfaces such as glass or by solutions of certain compounds , notably ellagic acid .
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 .
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 .
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 .
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 .
Hageman factor ( HF , Factor XII ) is activated by glass , collagen , and ellagic acid , and initiates blood coagulation via the intrinsic pathway .
Factor XII activation markers do not reflect FXII dependence of thrombin generation induced by polyvinylchloride .
Activation of Hageman factor in solid and fluid phases . ~@~ A critical role of kallikrein .
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 ) .
Substrates of Hageman factor . ~@~ I . ~@~ Isolation and characterization of human factor XI ( PTA ) and inhibition of the activated enzyme by alpha 1-antitrypsin .
Factor XII activation also contributed to the stimulating effect of collagen on thrombin generation in plasma , and increased the effect of platelets via glycoprotein VI activation .
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 ) .
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 deficiency is associated with a prolonged activated partial thromboplastin time and activated clotting time used for monitoring during cardiopulmonary bypass .
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 .
Hageman factor previously activated by ellagic acid ( factor XIIa ) retained full enzymatic activity in the presence of microfilarial extract ( 01 mg/ml ) .
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 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 is activated by collagen , i.e. , whenever the vascular endothelium is injured , and to a lesser extent also by """"activated"""" blood platelets .
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 .
Hageman factor , HMrK and prekallikrein were required for maximal rates of activation of factor XI .
Hageman factor Dependent Intrinsic Fibrinolysis ( HDIF ) was calculated by subtracting the HIIF from the activity obtained after activation of the """"resting plasma"""" by dextran sulfate .
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 .
Factor XII in the plasma preparation was activated to unfragmented factor XIIa by adsorption to kaolin , and assayed as prekallikrein activator ( PKA ) .
Hageman factor activation and tight junction disruption in mice challenged with attenuated endotoxin .
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 and other plasma proteases first activate small amounts of C1s ; the resulting C1 esterase then activates the bulk of C1s .
Factor XII , PPK and HMWK are necessary for full activation .
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 .
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 ) .
Hageman factor substrates . ~@~ Human plasma prekallikrein : mechanism of activation by Hageman factor and participation in hageman factor-dependent fibrinolysis .
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 ) .
Hageman factor dependent activation and its relationship to lethal Pseudomonas aeruginosa burn wound infections .
Factor XII does not initiate prekallikrein activation on endothelial cells .
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 .
Hageman factor - and tissue factor-dependent activation of human blood/plasma coagulation , and binding to human monocytes , endothelial cells and platelets were quantified in_vitro using naked and PEGylated ORMOSIL-NPs .
FXII is activated in_vivo by a variety of negatively-charged polyphosphates , which include extracellular RNA , DNA and inorganic polyphosphate ( PolyP ) that are released during cell damage and infection .
Hageman factor : alterations in physical properties during activation .
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 .
FXII activation is secondary to PK activation and contributes to the extent of measured enzymatic activity .
Hageman factor fragments , at a protein concentration equivalent to whole Hageman factor , activated plasminogen to a lesser extent .
Factor XII deficiency is not associated with bleeding , which suggests that another mechanism for factor XI activation exists in_vivo .
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 .
FXII activity was measured by an activated partial thromboplastin time ( APTT ) assay .
Factor XII activation is essential to sustain the procoagulant effects of particulate matter .
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 .
Cold activation of complement i . ~@~ presence of coagulation-related activator .
The fibrinolytic pathway of human plasma . ~@~ II . ~@~ The generation of chemotactic activity by activation of plasminogen proactivator .
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 .
A prealbumin activator of prekallikrein . ~@~ II . ~@~ Derivation of activators of prekallikrein from active Hageman factor by digestion with plasmin .
The binding and cleavage characteristics of human Hageman factor during contact activation . ~@~ A comparison of normal plasma with plasmas deficient in factor XI , prekallikrein , or high molecular weight kininogen .
Guinea pig macroalbumin . ~@~ A major inhibitor of activated Hageman factor in plasma with an alpha 2-macroglobulin-like nature .
Activated coagulation Factor XII ( FXIIa ) infusion increases peripheral resistance ( TPR ) and mean arterial pressure ( MAP ) of Brown Norway but not plasma kininogen deficient Brown Norway Katholiek ( BNK ) rats .
Surface-independent acceleration of factor XII activation by zinc ions . ~@~ II . ~@~ Direct binding and fluorescence studies .
PATHOGENESIS OF INFLAMMATION . ~@~ II . ~@~ IN VIVO OBSERVATIONS OF THE INFLAMMATORY EFFECTS OF ACTIVATED HAGEMAN FACTOR AND BRADYKININ .
The reinfarction group of patients had a significantly lower median factor XII-dependent fibrinolytic activity ( 24.9 blood activating units ( BAU ) .
Surface-independent acceleration of factor XII activation by zinc ions . ~@~ I . ~@~ Kinetic characterization of the metal ion rate enhancement .
Prekallikrein activation , C1 esterase inhibitor , and factor XII as predictors of adverse reaction to contrast media . ~@~ A prospective study .
The effect of dalteparin on coagulation activation during pregnancy in women with thrombophilia . ~@~ A randomized trial .
Fletcher factor deficiency . ~@~ A diminished rate of Hageman factor activation caused by absence of prekallikrein with abnormalities of coagulation , fibrinolysis , chemotactic activity , and kinin generation .
Activation of human plasma prekallikrein by Pseudomonas aeruginosa elastase . ~@~ II . ~@~ Kinetic analysis and identification of scissile bond of prekallikrein in the activation .
A prealbumin activator of prekallikrein. 3 . ~@~ Appearance of chemotactic activity for human neutrophils by the conversion of human prekallikrein to kallikrein .
Studies on prekallikrein of bovine plasma . ~@~ II . ~@~ Activation of prekallikrein with proteinases and properties of kallikrein activated by bovine Hageman factor .
Human blood coagulation factor XII ( FXII ; 80 kDa ) contains a C-terminal serine protease zymogen domain , which becomes activated upon contacting a negative surface .
Contact factor XII ( FXII ) , an upstream activator of FXI , also contributes to experimental stroke , but is not required for hemostasis .
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 ( FXIIa ) , FXII zymogen ( FXII ) , FXIIa-C1-esterase inhibitor ( C1-inhibitor ) , Kallikrein-C1-inhibitor , FXIa-C1-inhibitor and FXIa-alpha1-antitrypsin ( AT-inhibitor ) complexes were measured by Enzyme-linked immunosorbent assy ( ELISA ) methodology .
The F12 -4T allele , associated with reduced levels of FXII ( P < 0001 ) , also significantly delayed the activated partial thromboplastin time ( aPTT ) expressed as aPTTr ( ratio sample plasma/normal pooled plasma ) .
Activated factor XII ( FXIIa ) is selectively inhibited by corn Hageman factor inhibitor ( CHFI ) among other plasma proteases .
Activated Hageman factor , when injected into the rabbit ear chamber , produces a delayed and prolonged inflammatory response characterized by prominent sticking and emigration of leucocytes .
When FXII was added with the PK , maximal activation occurred within 7.5-10 min .
Activated Hageman factor ( HFa ) exhibits two molecular forms .
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% .
PolyP-driven factor XII activation triggered release of the inflammatory mediator bradykinin by plasma kallikrein-mediated kininogen processing .
[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 was not associated with risk .
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 .
Activation of Hageman factor ( factor XII ) by sulfatides and other agents in the absence of plasma proteases .
The Hageman factor fragment ( HFf ) concentrate was prepared from acetone and dextran sulphate activated human plasma by chromatography on a CM-Sephadex column .
Rabbit Hageman factor was proteolytically cleaved and activated by a homogenate prepared from cultured rabbit endothelial cells .
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 .
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 .
Coagulation FXII is activated on contact with lipoprotein particles .
Homozygous FXII knockout ( FXII(-)/(-) ) mice showed no FXII plasma activity and had a markedly prolonged activated partial thromboplastin time ( aPTT ) .
Isolated Hageman factor was far more sensitive to activation than Hageman factor in plasma or serum .
Activated Factor XII ( XIIa ) is believed to participate in a number of pathophysiological processes including inflammation , thrombosis and fibrinolysis .
Augmented Hageman factor and prolactin titers , enhanced cold activation of factor VII , and spontaneous shortening of prothrombin time in survivors of myocardial infarction .
Activation of Hageman factor ( factor XII ) by bismuth subgallate , a hemostatic agent .
Exogenous Hageman factor fragment added to plasma induced the rapid formation of C1In-K complexes , whereas there was an appreciable delay when the plasma contact system was activated by the addition of kaolin .
Activated factor XII type A and B-type natriuretic peptide are complementary and incremental predictors of mortality in patients following admission with acute coronary syndrome .
Since fXII deficiency does not impair hemostasis , targeted inhibition of fXI activation by fXIIa may be a useful antithrombotic strategy associated with a low risk of bleeding complications .
The Hageman factor and the complement system may also be activated .
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 .
Thus factor XII is critical for activation to proceed .
Activated FXII relates to both extent of coronary atheroma and to a past history of myocardial infarction and clusters with features of insulin resistance .
Activated factor XII in rheumatoid arthritis .
Activated factor XII ( FXIIa ) is involved in vascular injury and repair , participating in inflammation , thrombosis , and fibrinolysis .
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 .
Activated FXII ( alphaFXIIa ) brings about reciprocal activation of FXII and kallikrein that by further hydrolysis produces the free catalytic domain ( betaFXIIa ; 28 kDa ) .
Activated factor XII was measured to exclude XII activation as a cause of the low XII activity levels .
Although Hageman factor does undergo cleavage and activation in the absence of prekallikrein or high MW kininogen , the rate is approximately 50 and 100 times slower than when these molecules are present .
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 .
Activation of Hageman factor ( Factor XII ) upon exposure to negatively charged agents has been attributed to proteolytic cleavage of this molecule .
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 .
Both FXII and the complex plasma prekallikrein/high molecular mass kininogen become activated when they bind , in a Zn2+-dependent manner , to receptors on human umbilical vein endothelial cells ( HUVEC ) .
Mice lacking factor XII ( fXII ) or factor XI ( fXI ) are resistant to experimentally-induced thrombosis , suggesting fXIIa activation of fXI contributes to thrombus formation in_vivo .
Activated FXII antigen was not significantly raised in plasma stored for 18 to 24 hours , but levels of prothrombin fragment 1 + 2 were slightly increased ( 088 ng/mL , 18-24 hr ; 065 ng/mL , < 8 hr ) .
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 .
Human Hageman factor , a plasma proteinase zymogen , was activated in_vitro under a near physiological condition ( pH 78 , ionic strength I = 014 , 37 degrees C ) by Pseudomonas aeruginosa elastase , which is a zinc-dependent tissue destructive neutral proteinase .
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 .
Activated Factor XII ( Factor XIIa , 80,000 kDa ) is further cleaved by kallikrein or plasmin to yield Factor XII fragment ( Factor XIIf , 30,000 kDa ) and Factor XIIf can activate the C1r subcomponent of C1 , particularly when C1 INH ( which inhibits Factor XIIf ) is absent .
Once Hageman factor is activated on the surface , it cleaves and activates clotting factor XI .
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 .
The Hageman factor dependent pathways are influenced by several control proteins which modulate the extent of activation and biologic activity of these enzyme substrates ( Fig 1 ) .
Contact activation of blood factor XII ( FXII , Hageman factor ) in neat-buffer solution exhibits a parabolic profile when scaled as a function of silanized-glass-particle activator surface energy ( measured as advancing water adhesion tension tau(a) (o) =gamma ( lv ) (o) cos theta in dyne/cm , where gamma ( lv ) (o) is water interfacial tension in dyne/cm and theta is the advancing contact angle ) .
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 .
Activation of factor XII and prekallikrein with polysaccharide sulfates and sulfatides : comparison with kaolin-mediated activation .
Mechanisms for Hageman factor activation and role of HMW kininogen as a coagulation cofactor .
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 .
Direct evidence for Hageman factor ( factor XII ) activation by bacterial lipopolysaccharides ( endotoxins ) .
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 .
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 .
Activation of factor XII in human plasma : protection by benzamidine of the cofactor function of high molecular weight kininogen .
Exposure of Hageman Factor ( bound to a negatively charged surface ) to BK-A led to the proteolytic cleavage of Hageman Factor producing a 28,000 molecular weight fragment ( HFa ) which is functionally active and capable of activating prekallikrein to kallikrein .
Surface bound Hageman Factor interacts with complexes of prekallikrein and HMW-kininogen as well as Factor XI and HMW-kininogen to form activated Hageman factor , kallikrein , and Factor XIa .
Activation of factor XII by tobacco glycoprotein .
Bismuth subgallate activates factor XII ( Hageman factor ) and , therefore , markedly accelerates the cascade of blood clotting .
Activation of factor XII in rat plasma : protection by benzamidine of the cofactor function of high molecular weight kininogen .
Activation of Factor XII in solution was equally well catalyzed by kallikrein and its light chain .
Activation of Hageman factor in solution ( fluid phase ) was obtained with kallikrein , plasmin , and Factor XI ( plasma thromboplastin antecedent ) .
Levels of factor XII were reduced in 2 patients who had single factor assays performed , consistent with activation of the kallikrein-kinin system .
Decrease of FXII : C may play an important role in cerebral thrombosis by reducing activation of plasminogen .
The ACTIVATED FACTOR XII kit ( Shield Diagnostics ) has recently been commercially available , and the reference range was reported in the instruction manual .
Fragments of Hageman factor and perhaps kallikrein can also activate factor VII .
Purified human factor XII zymogen was not activated by heparin through an autoactivation mechanism , but was activated in the presence of purified prekallikrein .
Activation of Hageman factor was accompanied by cleavage of the molecule into several fragments , one of which possessed prekallikrein-activating ( PKA ) and clot-promoting properties .
Activation of human Hageman factor ( factor XII ) in the presence of zinc and phosphate ions .
Association of factor XII in this conformation on the activating surface was suggested to be responsible for the autoactivation .
Elevated activated FXII ( FXIIa ) levels have been previously associated with CHD .
Inhibition of Hageman factor activation .
Studies on factor XII in porcine plasma : purification and its conversion to activated form by porcine plasma kallikrein .
Activation of Hageman factor by L-homocystine .
Activation of FXII during haemodialysis .
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 .
Activation of hageman factor and prekallikrein and generation of kinin by various microbial proteinases .
No activated FXII could be demonstrated on the unfractionated heparin surface , whereas on the low-affinity heparin surface nearly all FXII underwent spontaneous activation .
Activation of factor XII initiates coagulation by the intrinsic coagulation pathway and activates complement .
Activation of FXII is elicited by fibrin during thrombotic reactions in_vitro and in_vivo , and fibrin acts as a heparin-like co-factor and regulates AT .
Activation of Hageman factor by collagen .
Activation of Hageman factor by LPS contrasts with fluid-phase activation ( e.g. , by kallikrein or trypsin ) in that no cleavage to lower molecular weight fragments occurs .
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 .
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 ) .
Studies with purified Hageman factor ( factor XII ) demonstrate that this inhibitory property is directed against the activation of Hageman factor .
(a) Purified Hageman factor , activated on negatively charged surfaces retained its native mol wt of 80-90,000 .
Assessment of Hageman factor activation in human plasma : quantification of activated Hageman factor-C1 inactivator complexes by an enzyme-linked differential antibody immunosorbent assay .
Activation of Hageman factor was associated with three different structural changes in the molecule :
Surface activation of factor XII ( Hageman factor ) --critical role of high molecular weight kininogen and another potentiator ) .
Activated human Hageman factor ( XII ) .
Activation of factor XII in acetone-treated human plasma : significance of the functional state of plasma kallikrein for the extent of activation .
Sephadex-ellagic acid-exposed Hageman factor , whether purified or in plasma , activated plasma thromboplastin antecedent , but only when high molecular weight kininogen was presnet .
Activation of factor XII and prekallikrein with cholesterol sulfate .
The autoactivation of factor XII ( Hageman factor ) induced by low-Mr heparin and dextran sulphate . ~@~ The effect of the Mr of the activating polyanion .
Activation of Hageman factor by ellagic acid was also inhibited by certain constituents of eosinophils , including eosinophil peroxidase , eosinophil major basic protein and eosinophil cationic protein .
The human Factor XII gene codes for a serine proteinase synthesized in liver that activates both the coagulation and the fibrinolytic cascades .
As activated factor XII ( factor XIIa or factor XIIf ) forms , it converts prekallikrein ( PK ) to kallikrein and kallikrein cleaves high molecular weight kininogen ( HK ) to release bradykinin .
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 .
Contact activation of blood factor XII ( FXII , Hageman factor ) is moderated by the protein composition of the fluid phase in which FXII is dissolved .
Thus , FXII activation in both buffer and protein-containing solutions does not exhibit characteristics of a biochemical reaction but rather appears to be a """"mechanochemical"""" reaction induced by FXII molecule interactions with hydrophilic activator particles that do not formally adsorb blood proteins from solution .
However , factor XII was not activated and fibrinolysis was not increased .
Thus both Hageman factor and prekallikrein are needed for optimal contact activation of prorenin .
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 .
L-Homocystine activates Hageman factor , as demonstrated by its capacity to initiate clotting and to induce the evolution of plasma kinins .
Rather , FXII activation in the presence of plasma proteins leads to an apparent specificity for hydrophilic surfaces that is actually due to a relative diminution of the FXII-- > FXIIa reaction at hydrophobic surfaces .
Occidentalis activates factor XII in high concentrations , which could account for its procoagulant effect at high doses on rats .
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 Hageman factor and initiation of hepatic vein thrombosis in the hyperlipemic rat .
Activation of Hageman factor by lipopolysaccharides of Bacteroides fragilis , Bacteroides vulgatus , and Fusobacterium mortiferum .
Activation of factor XII by dextran sulfate : the basis for an assay of factor XII .
Targeting polyphosphate-mediated factor XII activation offers the exciting possibility for a safe anticoagulation with minimal therapy-associated bleeding .
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 .
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 .
Therefore , both Hageman factor and prekallikrein were required for alkaline phase activation to occur .
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 relative proportions of enzymes with amidolytic or procoagulant activity produced by contact activation of the blood zymogen factor XII ( FXII , Hageman factor ) in buffer solution depends on activator surface chemistry/energy .
The production of factor XII fragment on in_vitro activation of plasma with HAE has also been observed .
The effects of FXII deficiency were not mimicked by the addition of corn trypsin inhibitor but were confirmed by inhibiting activated FXI .
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 .
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 .
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 ) .
However , all FXII activation markers in plasma failed to detect contact activation .
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 .
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 .
The initial step in activation of the plasma kinin system is activation of Hageman factor ( coagulation factor XII ) and/or plasma prekallikrein .
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 .
Increased expression of FXII in ESC during decidualisation suggests that the kallikrein-kininogen-kinin system may be activated during the implantation of human embryos .
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 ) .
Bismuth subgallate activates Factor XII and therefore accelerates the coagulation cascade .
The suppression of FXII activation on the unfractionated heparin surface was investigated by using plasma depleted of antithrombin , complement C1 esterase inhibitor , or both .
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 .
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 .
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 .
And yet , it is herein shown that activation of the blood zymogen factor XII ( Hageman factor , FXII ) dissolved in buffer , protein cocktail , heat-denatured serum , and FXI deficient plasma does not exhibit activator surface-area dependence .
Measurement of activated factor XII in health and disease .
Activation of human Hageman factor by a leukocytic protease .
The activation of factor XII initiates the intrinsic coagulation pathway , which is monitored by APTT .
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 .
Secondary fibrinolysis or Hageman Factor activation mediated by immune complexes .
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 .
Activation of rabbit Hageman factor with trypsin resulted in cleavage of the molecule into three fragments , each of 30,000 mol wt as noted previously .
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 .
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 ) .
The activation of Hageman factor in solid and fluid phase has been analyzed .
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 .
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 .
Levels of activated FXII in survivors of myocardial infarction--association with circulating risk factors and extent of coronary artery disease .
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 .
Prekallikrein activator ( Hageman factor fragment ) in human plasma fractions .
The activation of factor XII by plasma kallikrein ( reaction 1 ) and the activation of prekallikrein by factor XIIa ( reaction 2 ) .
XI with activated factor XII ( beta-XIIa ) .
As two examples , the novel procedure is used to analyse the autocatalytic activation of bovine trypsinogen and human blood coagulation factor XII ( Hageman factor ) .
Functional studies included real time quantitative polymerase chain reaction , nephelometry , and Western blot for alpha-2-macroglobulin ( A2M ) and activated partial thromboplastin time measurement for coagulation factor XII ( FXII ) .
The structure of Hageman factor , isolated from human plasma , was analyzed before and after enzymatic activation .
Surface binding of Hageman factor enhanced its cleavage by plasmin , activated Factor XI , and trypsin by 100-fold , 30-fold , and 5-fold , respectively .
Thus , physiologic FXII expression on HUVECs is secondary to HK binding and highly restricted in its ability to initiate prekallikrein or FXI activation .
Role of the Hageman factor in activating fibrinolysis. 3 .
However , because factor XII deficiency is not associated with any bleeding disorder , platelet-driven factor XII activation was believed to be an in_vitro artefact with no importance for coagulation in_vivo .
Incubation of active Hageman factor with streptokinase-activated plasminogen resulted in enhanced ability of the mixture to activate prekallikrein .
Finally , the intrinsic coagulation cascade , activated by coagulation factor XII ( FXII ) , has only recently been identified as another important mediator of thrombosis in cerebrovascular disease , thereby disproving established concepts .
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 ) .
Role of surface in surface-dependent activation of Hageman factor ( blood coagulation factor XII ) .
5,10-methylene tetrahydrofolate reductase ( MTHFR ) C677T , coagulation factor V ( F5 ) Leiden , coagulation factor II ( F2 , also known as prothrombin ) G20210A , coagulation factor XII ( F12 ) C46T , coagulation factor XIII A1 subunit ( F13A1 ) Val34Leu , serpine1 ( SERPINE1 , also known as plasminogen activator inhibitor-1 ) 4G/5G , protein Z ( PROZ ) -A13G , angiotensin I-converting enzyme ( ACE ) I/D , angiotensinogen ( AGT ) Met325Thr , and carboxypeptidase B2 ( CPB2 , also known as thrombin-activatable fibrinolysis inhibitor ) C1040T .
Despite absence of Hageman factor , evidence for activation of complement by the classic pathway and thromboembolic phenomenon was observed .
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 ) .
The activation of Hageman factor in acute inflammatory reactions could mediate the early congestion of lymph nodes .
Misfolded proteins activate factor XII in humans , leading to kallikrein formation without initiating coagulation .
Activation of human Hageman factor by Pseudomonas aeruginosa elastase in the presence or absence of negatively charged substance in_vitro .
Contact activation of Hageman factor and kallikrein enhanced activation of the classical pathway up to C3 conversion .
In addition , factor XII activation induces disordered hemostasis , which is related to increased fibrinolysis and a possible disturbance in platelet function .
A high activated factor XII was associated with increased CHD risk , but low levels were not protective .
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 .
Inhibition of activated factor XII by antithrombin-heparin cofactor .
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 .
Activation of prekallikrein FXII , FXI , and prothrombin was measured with sensitive enzyme-linked immunosorbent assays ( ELISAs ) , and FXI activation was measured with a novel enzyme capture assay that detects noncomplexed FXIa .
The activation of Hageman factor , followed by complement cleavage leading to liberation of various chemical mediators , can be initiated by exposure of negatively charged tissue components due to trauma and infection .
The cell-bound activated factor XII was also able to activate prekallikrein .
Fibrin clots elicited FXII activation and acted as co-factors for AT .
At prekallikrein and factor XII levels equal to those in plasma , reciprocal activation is approximately 2000-fold more rapid than autoactivation .
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 .
Prekallikrein activation by Hageman factor : potentiation by proteins in the absence of high molecular weight kininogen .
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 .
C1INH inhibits activated factor XII ( FXIIa ) , activated factor XI ( FXIa ) , and kallikrein .
We enrolled 3,094 Japanese type 2 diabetic subjects ( 627% male ; aged 615 +/- 84 years ) and determined their genotypes regarding matrix metalloproteinase 9 C-1562T , coagulation factor XII ( F12 ) C46T , von Willebrand factor ( VWF ) G-1051A , and plasminogen activator inhibitor ( PAI-1 ) 675 4G/5G polymorphisms .
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 ) .
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 .
Activation of plasma Hageman factor and kallikrein in ongoing allergic reactions in the skin .
The activation of factor XII by the proteases factor XIIa and kallikrein is known to be greatly enhanced by certain negatively charged surfaces .
Autodigestion of activated Hageman factor ( HFa ) yields a 40,000-mol wt activated enzyme as well as Hageman factor fragment ( HFf ) ; HFf consists of two molecular weight species of 28,500 and 30,000 .
Levels of activated factor XII ( FXIIa ) and VII ( FVIIa ) were determined in 100 women with uneventful pregnancies .
Incubation of native Hageman factor with PPACMK does not destroy its procoagulant activity , even in the presence of the activator dextran sulphate , but PPACMK inhibits autoactivation of Hageman factor , suggesting that no active site is formed in uncleaved , surface-bound Hageman factor .
Activation of rabbit Hageman factor by homogenates of cultured rabbit endothelial cells .
This effectively activates factor XII and releases platelet factor 3 , thereby markedly shortening the clotting time .
Sulfatides greatly stimulate Factor XII activation .
Known natural activators of FXII and the contact system include heparin , sulfatides , phospholipids , endotoxin , and urate crystals .
Pollen extract directly activated factor XII in the coagulation cascade .
Highly purified preparations of Hageman factor , a potent clotpromoting agent in normal mammalian plasma , had a sedimentation coefficient of approximately 5S before activation .
Inhibition of the activation of Hageman factor ( factor XII ) by soluble human placental collagens types III , IV , and V .
To this end , we performed extensive experimentation in_vitro and in_vivo in an attempt to verify the claim that factor XII ( FXII ) is primarily activated by stimulated platelets .
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 .
The genetic relationships between the kringle domains of human plasminogen , prothrombin , tissue plasminogen activator , urokinase , and coagulation factor XII .
In_vivo activation of the Hageman factor dependent pathway frequently results in an abnormal CIE and a low PKA antigen level .
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 ) .
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 .
Glucocorticoids prevent activation of factor XII by endotoxin in_vivo and decrease production of tissue factor by macrophages .
The contact system is a plasma protease cascade that is initiated by coagulation factor XII activation on cardiovascular cells .
Interactions Outside the Proteinase-binding Loop Contribute Significantly to the Inhibition of Activated Coagulation Factor XII by Its Canonical Inhibitor from Corn .
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 ) .
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 .
Activation of prekallikrein by Hageman factor was found to involve cleavage of the single peptide bond on the disulfide-bridged polypeptide chain , and no change of molecular weight was observed during the activation .
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 .
Furthermore , pre-incubation of Hageman Factor with tryptase did not diminish the subsequent activation of Hageman Factor by trypsin .
Because activation of the contact proteases factor XII ( FXII ) , prekallikrein , and factor XI ( FXI ) can trigger coagulation and inflammatory responses , the contact factors have been considered potential targets for the treatment of sepsis .
We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII ( FXII ) and by supporting its activation through the release of neutrophil extracellular traps ( NETs ) .
We describe the first sandwich enzyme-linked immunosorbent assay ( ELISA ) capable of recognizing both rat and human activated coagulation Factor XII ( FXIIa ) .
The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII , which promotes inflammation and the intrinsic coagulation pathway .
With kaolin , activated Factor XII ( XII(a) ) was the apparent principal activator .
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 .
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 .
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 .
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 .
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 .
In contrast , once Hageman factor was activated by kaolin , its clot-promoting properties were not inhibited by beta 2-glycoprotein I .
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 .
Activation of human blood plasma coagulation by contact with hydrophilic or hydrophobic surfaces ( procoagulants ) is dominated by kallikrein ( Kal ) -mediated activation of the blood zymogen FXII ( Hageman Factor ) .
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 .
Fibronectin binds to fibrin and collagen reversibly and crosslinks to these filamentous proteins catalyzed by the activated blood coagulation factor XII ( plasma transglutaminase ) .
By inducing BK ( bradykinin ) -stimulated adrenomedullary catecholamine release , bolus injection of the BETA-fragment of activated plasma coagulation Factor XII ( BETA-FXIIa ) transiently elevates BP ( blood pressure ) and HR ( heart rate ) of anaesthetized , vagotomized , ganglion-blocked , captopril-treated bioassay rats .
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 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 ) .
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 .
Contact system activation , in_vitro , is triggered by activation of factor XII ( FXII ) on binding to an activator , such as negatively charged surfaces .
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 .
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 .
The role of clotting factor XII in the activation of the complement subunit C1s to C1 esterase was examined.2 .
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 ) .
Activation and consumption of Hageman factor in the anaphylactic shock of the rat .
Inhibition of the activation of Hageman factor ( factor XII ) by peripheral blood cells .
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 .
Increased levels of activated Hageman factor ( ng/ml/hr ) were detected at antigen sites ( 135 +/- 060 ) compared with buffer sites ( 011 +/- 005 ) , ( p less than 001 ) , in 8 of 10 subjects .
Changes of plasma activated Factor XII type A ( XIIaA ) concentrations following percutaneous coronary intervention ( PCI ) .
Enzymatic activities of activated and zymogen forms of human Hageman factor ( factor XII ) .
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 .
Inhibition of the activation of Hageman factor ( factor XII ) by beta 2-glycoprotein I .
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 .
Direct potential-mediated and time-controlled activation of purified human factor XII ( FXII ) immobilized on carbon has been demonstrated .
The binding of activated FXII to the ECM suggests that FXIIa may be a modulator of cellular adhesion , migration and vascularization .
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 .
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 .
Prothrombin activation fragment ( F12 ) is increased in pregnant patients with antiphospholipid antibodies .
The activated forms of Hageman factor , Hfa and HFf , were also inactivated by PPACMK with rate constants 0.82 and 0.72 min-1 .
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 .
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 .
Contact activation is initiated when the plasma proteins , Hageman factor ( factor XII ) , prekallikrein and high molecular weight kininogen interact with negatively charged materials .
In the physiological route , gluey particles with negative charges can activate intrinsic coagulation systems by activating the blood coagulation factor XII after FHF dissolution .
These studies indicate that Hageman factor has a hitherto unsuspected function , the direct activation of plasminogen .
No further activation of factor XII was obtained at 0.80 microgram/ml .
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 .
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 .
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 .
No activation occurred if Factor XII was omitted .
The initial step in the formation of thrombin via the intrinsic pathway is the activation of Hageman factor ( factor XII ) .
Activation of coagulation required the presence of fully activatable platelets and was not ascribable to platelet tissue factor , whereas targeting polyphosphate with phosphatase reduced thrombin generation even when factor XII ( FXII ) was blocked or absent .
Furthermore , inhibition of factor XII activation by lysozyme ( 20 mg/kg/min ) completely prevented hepatic vein thrombosis initiated by endotoxin in butter-fed animals .
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 .
In addition , activated factor XII ( 07 +/- 05 microg/L vs. 45 +/- 10 microg/L ) increased .
For decades it has been known that activated platelets promote plasma clotting and that the fibrin forming activity of activated platelets is dependent on blood coagulation factor XII .
HSV1-enhanced activation of purified FXII was confirmed by Western blot , but required prekallikrein .
Only the negatively charged amphiboles ( crocidolite and amosite ) are able to activate factor XII ( Hageman factor ) .
Inhibition of the activation of Hageman factor ( factor XII ) by aprotinin ( Trasylol )
It is well known that on artificial surfaces , binding and autoactivation of factor XII ( FXII ) is the initiating event of plasma prekallikrein ( PK ) activation .
Prothrombin activation fragment ( F12 ) is an index of in_vivo thrombin generation .
Mutations in the SERPING1 gene result in decreased secretion of functional C1INH and episodic activation of plasma kallikrein and Hageman factor ( FXII ) of the plasma contact system with cleavage of high molecular weight kininogen and generation of bradykinin .
ODSH has low affinity for anti-thrombin III , low anti-Xa , and anti-IIa anticoagulant activities and does not activate Hageman factor ( factor XII ) .
The plastic beads activate Hageman factor in normal human and mouse plasma ; the plastic beads induce vascular permeability-enhancing activity as measured in guinea pig skin and kinin-like activity in normal human and mouse plasma that is dependent on Hageman factor ; ellagic acid , an agent that activates Hageman factor in_vivo and is reported to diminish kininogen by consumptive depletion , markedly depresses the plastic bead granuloma .
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 .
Microfilarial extracts ( 01 mg/ml ) completely inhibited activation of Hageman factor ( factor XII , at 005 U/ml ) as measured in an amidolytic assay .
On exposure to purified FXII solution and plasma , all the tested materials adsorbed and activated FXII to varying degrees .
This work suggests that factor XII behaves as a negative acute phase protein with no signs of elevated activated XII levels in either group .
Instead , collagen appeared to accelerate clotting by activating Hageman factor ( factor XII ) on the basis of the following findings :
Inhibition of the activation of hageman factor ( factor XII ) by eosinophils and eosinophilic constituents .
In an earlier study , activated species of Hageman factor ( factor XII ) induced elaboration of interleukin-1 by human monocytes .
The peculiarities of the Hageman factor activation by trypsin were studied .
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 .
Inhibition of the activation of Hageman factor ( factor XII ) by complement subcomponent C1q .
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 .
Activated high molecular weight Hageman factor ( 75 Kd ) and Hageman factor carboxy-terminal fragments both formed complexes with purified C1(-) -inhibitor , but the Hageman factor fragments appeared to have a higher affinity for the C1(-) -inhibitor than activated Hageman factor .
This relates to contact phase activation with exaggerated kinin formation , and mutations in the coagulation factor XII gene have been identified in some affected families , but the cause of the disease has remained elusive in a majority of families .
Reciprocal proteolytic activation of Hageman factor and prekallikrein represents an essential step in the rapid activation of the contact phase .
Inhibition of the activation of Hageman factor ( factor XII ) by extracts of Schistosoma mansoni .
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 .
An HMG-I protein from human endothelial cells apparently is secreted and impairs activation of Hageman factor ( factor XII ) .
(c) Activation of human Hageman factor with kallikrein or plasmin was associated with cleavage of the molecule to 52,000 , 40,000 , and 28,000 mol wt fragments .
This effect of activated Hageman factor could not be shown during its incubation with normal siliconed plasma , nor could consumption of normal serum inhibition of C1 esterase be clearly shown .
Elevated fibrinogen , activated factor XII ( FXIIa ) , and factor VII coagulant activity ( FVIIc ) are associated with higher risk of fatal ischemic heart disease .
Influence of Zn2+ on the kinetic events that contribute to the 500-kDa dextran-sulfate-dependent activation of factor XII ( Hageman factor ) .
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 .
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 .
Contact activation in human plasma is triggered by zinc ion modulation of factor XII ( Hageman factor ) .
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 .
Crinale does not activate factor XII , while the polysaccharide from B .
Thus , activation of Hageman factor by negatively charged agents was not necessarily accompanied by molecular scission .
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 .
Inorganic polyphosphates ( polyP ) , which are secreted by activated platelets ( short-chain polyP ) and accumulate in some bacteria ( long-chain polyP ) , support the contact activation of factor XII ( FXII ) and accelerate the activation of FXI .
The activation of plasminogen by Hageman factor ( Factor XII ) and Hageman factor fragments .
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 ) .
This study was aimed at determining whether the antigen levels of coagulation factors ( factor XII , FXII , and FXI and prekallikrein ( PK ) are associated with MI and IS , and whether this association is independent of levels of activated protein-inhibitor complexes .
An enzyme-linked immunosorbent assay ( ELISA ) for the measurement of activated factor XII ( Hageman factor ) in human plasma .
In addition , in in_vitro activation tests of human plasma , nanosilica particles had greater potential than did conventional microscale silica particles to activate coagulation factor XII .
Explicit constants for the dextran-sulfate-mediated activation and autoactivation of purified human factor XII ( Hageman factor ) .
On endothelial cells , factor XII activation is secondary to prekallikrein activation and amplifies it .
Cold promoted activation and factor XII , prekallikrein and C1-inhibitor .
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 .
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 .
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 .
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 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 .
In this report , we describe a plausible mechanism of activation of the kinin-generating system , also known as the contact system or kininogen-kallikrein-kinin system , by the adsorption of its plasma-derived components such as high-molecular-mass kininogen ( HK ) , prekallikrein ( PK ) , and Hageman factor ( FXII ) to the cell surface of periodontal pathogen Porphyromonas gingivalis .
Ellagic acid ( EA ) has been identified to trigger the intrinsic coagulation system via activating coagulation factor XII .
Exposure of the plasma protein factor XII ( FXII ) to an anionic surface generates activated FXII that not only triggers the intrinsic pathway of blood coagulation through the activation of FXI but also mediates various vascular responses through activation of the plasma contact system .
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 .
After activation , the Hageman factor behaved as a much less soluble or larger molecule during ultracentrifugation and gel filtration .
Fibrinolytic properties of activated FXII .
Potential-mediated and time-controlled first order activation of factor XII ( Hageman factor ) adsorbed to carbon surfaces .
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 .
This HMG-I probably inhibits factor XII functions because its high positive charge favors competitive binding to an activating substance .
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 .
Functionally , the molecule is the precursor of the activator of prekallikrein ( Pre-PKA ) and evidence is presented that it is identical with Hageman factor ( clotting factor XII ) .
Plasma kallikrein activated to Hageman factor released kinin rapidly from bovine high molecular weight ( HMW ) kininogen .
Contributions of contact activation pathways of coagulation factor XII in plasma .
Inhibition of the activation of Hageman factor ( factor XII ) by human vascular endothelial cell culture supernates .
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 .
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 ) .
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 .
Interestingly , these polymers can also induce blood coagulation due to activation of factor XII ( FXII ) .
The current work addresses the hypothesis that HSV1-induced plasma coagulation also involves intrinsic pathway , factor VIII ( FVIII ) , and upstream contact activation pathway , factor XII ( FXII ) .
Molecular mechanisms of surface-dependent activation of Hageman factor ( Factor XII ) .
KKS signaling cascade is activated by activated factor XII ( FXIIa , Hageman factor ) - and prolylcarboxypeptidase ( PRCP ) -dependent pathways on endothelial cells .
These events clearly precede the death of the animal and appear to be initiated by an activation of coagulation factor XII ( Hageman ) .
The capacity to activate Hageman factor has been demonstrated to reside in the lipid A region of the LPS molecule .
The effect of chemical modification of basic amino acid residues on the activation and amidolytic activity of Hageman factor ( factor XII ) .
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 .
TGP-L and TGP-CSC contain polyphenol haptens that activate the factor XII ( Hageman factor ) dependent pathways of coagulation , fibrinolysis , and kinin generation in normal human plasma .
These findings demonstrated that Hageman factor , prekallikrein and proteins of the complement system are activated in B .
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 .
Prothrombin fragment 1.2 ( F12 ) is an activation peptide generated during a critical event of blood coagulation , the conversion of prothrombin to thrombin .
Patients with HAE experience angioedema because of a defective control of the plasma kinin-forming cascade that is activated through contact with negatively charged endothelial macromolecules leading to binding and auto-activation of coagulation factor XII , activation of prekallikrein to kallikrein by factor XIIa , and cleavage of high-molecular-weight kininogen by kallikrein to release the highly potent vasodilator bradykinin .
(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 .
Sepharose ion-exchange particles bearing strong Lewis acid/base functional groups ( sulfopropyl , carboxymethyl , quaternary ammonium , dimethyl aminoethyl , and iminodiacetic acid ) exhibiting high plasma protein adsorbent capacities are shown to be more efficient activators of blood factor XII in neat-buffer solution than either hydrophilic clean-glass particles or hydrophobic octyl sepharose particles ( FXII ( activator ) → ( surface ) FXIIa ; a .
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 .
Factor XIIa ( activated Hageman factor ) was isolated from bovine plasma by ammonium fractionation followed by heparin-agarose , carboxymethylcellulose , and arginine-agarose column chromatography .
Inhibition of the activation of Hageman factor ( factor XII ) by platelet factor 4 .
Washed platelets reconstituted in plasma obtained from two patients with coagulation factor XII deficiency were activated by oxidized cellulose with a prolonged lag phase .
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 .
A new enzyme-linked immunosorbent assay recognizing both rat and human activated coagulation Factor XII ( FXIIa ) .
The secondary structure of human Hageman factor ( factor XII ) and its alteration by activating agents .
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 .
A fragment of activated Hageman factor ( HFf ) has been demonstrated to activate the classical pathway of complement in a manner that is analogous to complement activation by antigen-antibody complexes or aggregated IgG .
Heparin activated the protease factor XII , which initiates bradykinin formation in plasma .
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 .
Blood contacting surfaces bind plasma proteins and trigger coagulation by activating factor XII ( FXII ) .
The role of prekallikrein and high-molecular-weight kininogen in the contact activation of Hageman factor ( factor XII ) by sulfatides and other agents .
Activation of highly purified Hageman factor occurred after it interacted with and became bound to a negatively charged surface .
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 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 .
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 .
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 ) .
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 .
Addition of intact activated Hageman factor corrected the coagulation , fibrinolytic , and chemotactic defects and addition of Hageman factor fragments corrected the fibrinolytic defect and partially corrected the chemotactic defect ; neither of these corrected the kinin-generating defect .
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 .
Inhibition of the activation of Hageman factor ( factor XII ) and of platelet aggregation by extracts of Brugia malayi microfilariae .
Coagulation time was measured by active partial thromboplastin time ( APTT ) test , which showed that MS coating is as inert as PS in activating blood coagulation factor XII .
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 .
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 ) .
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 .
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 ) .
We investigated the effects of amyloid precursor protein isoforms on activated Hageman factor ( factor XII ) , activated factor X ( Stuart factor ) , and thrombin .
A protein inhibitor ( CMTI-V ; Mr 7106 ) of trypsin and activated Hageman factor ( Factor XIIa ) , a serine protease involved in blood coagulation , has been isolated for the first time from pumpkin ( Cucurbita maxima ) seeds by means of trypsin-affinity chromatography and reverse phase high performance liquid chromatography ( HPLC ) .
Our data suggest that sulfatides stimulate Factor XII activation via two distinct mechanisms :
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 .
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 .
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 .
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 .
We have developed a large-scale method for recovering the corn inhibitor of trypsin and activated Hageman factor from a trypsin-agarose column predominantly in the single-chain form .
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 .
However it was not known how factor XII is activated by procoagulant platelets within the growing thrombus .
Factor XI deficiency is associated with a bleeding diathesis , but factor XII deficiency is not , indicating that , in normal hemostasis , factor XI must be activated in_vivo by a protease other than factor XIIa .
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 .
Thus , these results indicate that the enhancement of vascular permeability induced by the 56K protease is caused by an activation of Hageman factor by 56K protease followed by subsequent activation of cascade amplification , and resulted in kinin generation in_vivo .
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 .
These numbers indicate that the activity detectable in native Hageman factor is due to contamination with activated species .
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 .
C-reactive protein , homocysteine , cysteine , von Willebrand factor , activated factor XII and conventional risk factors were assayed or recorded .
It is concluded that , in addition to the potent hypercoagulability induced by the fat-rich diets , activation of Hageman factor consecutive to endotoxin injection is essential for production of the phenomenon of hepatic vein thrombosis .
Compared with unmodified catheters , CTI-coated catheters demonstrated (a) decreased adsorption of fibrinogen and fXII , (b) greater inhibition of fXIIa generated by catheter-induced autoactivation , (c) attenuated fXIIa-mediated activation of fXI and (d) longer plasma clotting times in the absence or presence of fondaparinux .
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 .
Although none of the dysfunctional C1(-) -INH proteins significantly impaired amidolysis by plasmin , all but one inhibited activated Hageman factor .
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 .
The results were compared to the influence of these membranes on the activation of purified FXII .
Whereas fXI deficiency is associated with a hemorrhagic disorder , factor XII deficiency is not , suggesting that fXI can be activated by other mechanisms in_vivo .
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 .
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 .
The zymogen is converted to PK by activated factor XII .
Thrombin-antithrombin complex levels were measured to provide evidence of thrombin generation.(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 .
HMW kininogen is a cofactor in the enzymatic activation of Hageman factor by kallikrein and it also augments the function of the activated Hageman factor generated .
The mechanism by which a fragment of activated Hageman factor ( HFf ) activates the classical pathway of complement in serum or platelet-poor plasma has been further delineated .
These results indicate that septic shock was induced through activation of the Hageman factor dependent system by the bacteria-produced elastase which survived alpha 2M in the circulation .
Initial experiments were required to find a procedure for characterizing the immobilization of FXII and its activated form , factor XIIa ( FXIIa ) .
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 .
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 .
Thus , basic amino acid residues essential to the activation or activity of Hageman factor appear to be variably accessible to chemical modification .
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 ) .
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 .
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 .
By using mixtures of deficient plasmas and pooled normal plasma or purified factors it was proved that prekallikrein was the factor determined and that more than 10% ( of normal plasma concentration ) of FXII and HMW kininogen were essential for the activation of prekallikrein in our method .
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 .
Blood samples were taken for measurement of fibrinogen , factor VIIc ( FVIIc ) , factor VIIIc , prothrombin fragment F1.2 ( F12 ) , tissue plasminogen activator , and von Willebrand factor .
To the contrary , these collagen species inhibited activation of Hageman factor by glass or ellagic acid .
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 ) .
Fibrin formation in laminin-coated capillaries was abrogated by an antibody that interferes with FXI activation by activated FXII , or an antibody that blocks activated FXI activation of FIX .
Addition of increasing quantities of either of the major forms of activated Hageman factor ( HFa or HFf ) to normal plasma or to Hageman factor-deficient plasma leads to a dose-dependent increase in activated HF-C1 INH complexes .
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 .
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 .
In this paper we report the effect of sulfatides on rate constants of Factor XII activation by kallikrein and its isolated light chain .
We conclude that antithrombin and the antithrombin-binding sequence in the surface-immobilized heparin are essential for the prevention of surface activation of FXII and triggering of the intrinsic coagulation system .
D-dimer and prothrombin activation peptide ( F12 ) levels increased in a similar pattern for both groups during and after CPB .
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 .
Probing single-stranded DNA and its biomolecular interactions through direct catalytic activation of factor XII , a protease of the blood coagulation cascade .
Markers of thrombin generation [thrombin-antithrombin complexes ( TAT ) and prothrombin 1.2 fragments ( F12 ) ] and markers of platelet activation [soluble CD40 ligand ( sCD40L ) and P-selectin] were determined in the supernatant of blood samples obtained from a microvascular injury site .
Fibrin clots were incubated with purified FXII or whole blood , and the activation and regulation of FXII were studied .
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 ) .
Inhibition is apparently specific for the enzymatic activation of Factor XI ( pre-PTA ) by Factor XIIa ( activated Hageman factor ) .
Cabbage seed protease inhibitor : ~@~ a slow , tight-binding inhibitor of trypsin with activity toward thrombin , activated Stuart factor ( factor Xa ) , activated Hageman factor ( factor XIIa ) , and plasmin .
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 :
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 only preparations of immunoglobulins capable of activating Hageman factor were found to be contaminated with bacteria .
Results to date indicate that antithrombin III controls the activity of both thrombin and Factor Xa , C-1-esterase inhibitor controls kallikrein and probably activated Hageman Factor ( Factor XIIa ) , and alpha-2-antiplasmin controls plasmin activity .
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 .
The activation of the kinin cascade by Df-proteinase was examined in_vitro by using purified guinea pig Hageman factor ( HF ) , prekallikrein ( PK ) and high-molecular-weight kininogen ( HMWK ) and the effect of this proteinase on endogenous human plasma proteinase inhibitors ( serpins ) and alpha 2-macroglobulin was tested .
By means of contact of the vessel contents with the collagen , there is an additional activation of the coagulation system by factor XII possible .
Normally , kallikrein is formed in intrinsic hemostasis and activates factor XII .
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 .
In addition , pre-incubation of dimiconin with FXII effectively inhibited FXIIa activity whereas dimiconin did not affect already activated FXIIa , indicating that dimiconin inhibits the activation of FXII but not the enzymatic activity of FXIIa .
These results indicated that the autoactivation and the kallikrein activation of factor XII were dependent on different properties of the surface component .
Paw oedema in the rat by carrageenin and kaolin partially caused by Hageman factor activation was potentiated by the new angiotensin converting enzyme ( ACE ) inhibitor 2-[N-[(S) -1-ethoxycarbonyl-3-phenylpropyl-L-alanyl]- ( lS , 3S,5S ) -2 - azabicyclo[3.3.0]octane-3-carboxylic acid] ( ramipril , Hoe 498 ) due to its inhibition of kininase II which results in increased bradykinin levels .
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 .
The activation of factors XII ( FXII ) and VII ( FVII ) has been shown to occur on the surface of lipoproteins in the presence of lipoprotein lipase and may be modulated by beta2glycoprotein-1 ( beta2GP1 ) .
We compared the major changes induced by ellagic acid ( EA ) , a Hageman factor activator , in normal rats and in kininogen-deficient Brown Norway rats .
Data obtained in the past few years have defined the molecular mechanisms of contact activation of the Hageman factor pathways of plasma , i.e. , the kinin-forming , intrinsic clotting and fibrinolytic systems .
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 .
[In_vivo activation of the kallikrein-kinin system of rats by human Hageman factor fragments] .
It is suggested from these results that t-AMCHA may initiate the true activation of the kallikrein system by activating the Hageman factor .
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 .
Endothelial cell expression ( or secretion ) of heat-shock protein 90 or prolylcarboxypeptidase can activate the prekallikrein-HK complex to generate bradykinin in the absence of factor XII , however factor XII is then secondarily activated by the kallikrein that results .
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 .
Pretreatment of plasma with antibodies that selectively inhibit FXI activation by activated FXII ( FXIIa ) or FIX ) activation by activated FXI ( FXIa ) were not able to inhibit the procoagulant effect of long or short-chain polyP in plasma .
Coating of PS-CO(2) with alb-hep conjugate significantly decreased contact activation ( FXII activation ) .
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 .
The addition of purified human factor XII to this plasma restored the increase in VIIc and the activation of factor XII .
Studies on a complex mechanism for the activation of plasminogen by kaolin and by chloroform : the participation of Hageman factor and additional cofactors .
Cholesterol sulfate was found to display a strong ability to trigger the activation of Factor XII and prekallikrein in the presence of HMW kininogen .
Activity is not affected by glass contact and is not inhibited by inhibitors of contact or enzymatic activation of Hageman factor ( hexadimethrine bromide , 100 mug/ml ; cytochrome C , 250 mug/ml ; spermidine , 2 mM ; phenylmethylsulfonylfluoride , 1 mM ) .
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 .
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 .
Functional correlation between kallikrein and factor XII activated in human plasma .
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 .
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 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 .
We found no evidence of a relationship between activated factor XII and disease .
Pumpkin seed inhibitor of human factor XIIa ( activated Hageman factor ) and bovine trypsin .
Kallikrein therefore functions as an activator of Hageman factor by a positive feedback mechanism and generates most of the activated Hageman factor during brief exposure of plasma to activating surfaces .
The phenomenon was inhibited by soybean trypsin inhibitor , a well known inhibitor of plasma kallikrein , and also by corn trypsin inhibitor , which is the best inhibitor of the activated Hageman factor .
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 .
The formation of BK in CSF after SAH is thought to be due to the contact activation of Hageman factor ( intrinsic factor ) in the subarachnoid space .
Addition of OT-2 , a monoclonal antibody inhibiting activated FXII , prevented the normalization of aPTT .
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 .
In this review , we focus on early studies of FXII and the identification of platelet FXII activation activity , and discuss recent findings of poly P in FXII activation and coagulation .
Studied have shown that upon platelet activation and secretion , poly P activates FXII , indicating that it is most likely the elusive platelet FXII activator .
The site of action of the factor deficient in the patients plasma appeared to be subsequent to the activation of Hageman factor and plasma prekallikrein .
The conditions for maximal activation of prekallikrein by the Hageman factor and its active fragment were selected .
The kallikrein produced can cleave high-molecular-weight kininogen to produce bradykinin and also recruit factor XII by enzymatically activating it .
A nanobody-based method for tracking factor XII activation in plasma .
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 .
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 ) .
The inositol-phospholipid-accelerated activation of prekallikrein by activated factor XII at physiological ionic strength requires zinc ions and high-Mr kininogen .
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 .
Unlike heparin alone , OSCS , is able to activate FXII in plasma and stably bind to FXIIa enhancing plasma KK activity and the induction of vasoactive mediators such as bradykinin ( BK ) , C3a and C5a .
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 .
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 .
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 .
For in_vitro studies , activation of guinea pig Hageman factor and prekallikrein was examined in purified systems as well as in plasma as a zymogen source .
Contact activation of blood plasma and factor XII by ion-exchange resins .
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 .
Pre-PTA was activated directly by activated Hageman factor or by Hageman factor prealbumin fragments .
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 .
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 .
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 .
This last phenomenon , in addition to that of an interference in_vivo with the mechanism of activation of Hageman factor , are believed to be responsible for prevention by glucocorticoids of endotoxin-induced disseminated intravascular coagulation .
In contrast , modification of amino groups in N-terminal and lysine residues inhibits activated Hageman factor .
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 .
Activation of RPK with either trypsin or rabbit Hageman factor ( active ) occurs by limited proteolytic cleavage , producing two disulfide-linked polypeptide chains with molecular weights of 55,000 and 35,000 .
The uninfluential role of the surface on FXIIa suggests that the solid surface activates FXII in biomaterial-induced blood coagulation but is not otherwise involved in FXIIa activity as described by the classical mechanism .
The circumstances in which activation is initiated by factor XII autoactivation or by these factor XII bypasses are yet to be defined .
Endotoxin treated with chromium chloride is less toxic to mice than the parent molecule , but can disrupt intestinal permeability barriers and has an enhanced ability to activate Hageman factor .
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 .
Characterization of bovine factor XIIa ( activated Hageman factor ) .
Both the plasminogen-activating activity and chemotactic activity produced by the interaction of Hageman factor fragments and plasminogen proactivator to yield plasminogen activator were inhibited by diisopropyl fluorophosphate ( DFP ) indicating an essential role for the enzymatic site in both these activities .
In contrast to the original assertion , platelet-derived polyphosphates were found to be weak activators of FXII , with a FXIIa-generating activity of <10% compared with equivalent concentrations of kaolin .
Inhibition of ellagic acid-induced activation of Hageman factor by both forms of amyloid precursor protein was enhanced by heparin .
Plasma clotting times were measured at different concentrations of thromboplastin with activated FXII inhibited ( FXIIa-inhibited Diluted Thromboplastin Time , FXIIaiDTT ) .
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 .
Interactions of C1(-) -inhibitors from normal persons and patients with type II hereditary angioneurotic edema with purified activated Hageman factor ( factor XIIa ) .
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 .
The natural surface appears to be vascular endothelial cells which express binding proteins for factor XII and HK , and activation can proceed along the cell surface .
A major inhibitor of the beta form of activated Hageman factor ( beta-HFa ) with an apparent molecular weight of 28,000 , which was reported as a strong permeability factor ( Yamamoto and Cochrane , Am J Pathol 1981 , 105 :
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 .
These results show that dimiconin is an inhibitor of the contact phase initiated by FXII activation in the blood coagulation cascade , which differs from the bioactivity of triabin .
Putting polyphosphates to the test : evidence against platelet-induced activation of factor XII .
However , when these molecules were incubated with the homogenate in the presence of Hageman factor , both Factor XI and prekallikrein were cleaved , demonstrating that Hageman factor had been activated by the endothelial cell homogenate .
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 .
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 .
In the postprandial state FVII is activated without apparent activation of FXII in plasma .
Similar findings were observed for mice deficient in factor XI , a substrate of activated FXII .
Previous studies have shown an increased risk of coronary heart disease with increased levels of activated factor XII ( FXIIa ) .
These results (i) show that an anionic hydrophilic surface is not a necessary cofactor for FXIIa-mediated hydrolysis of PK , ( ii ) indicate that PK hydrolysis does not need to occur by an activation complex assembled directly on an anionic , activating surface , ( iii ) confirms that contact activation of FXII ( autoactivation ) is not specific to anionic hydrophilic surfaces , and ( iv ) demonstrates that protein-adsorption competition is an essential feature that must be included in any comprehensive mechanism of surface-induced blood coagulation .
The data obtained emphasize the role of factor XII activation by adrenaline for physiological regulation of blood coagulability .
Factor (F) XII , originally called Hageman factor , plays an important role in the kallikrein-kinin system by activating prekallikrein .
The intrinsic pathway is triggered by activation of FXII associated with surface-bound kallikrein , which subsequently activates factor XI .
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 .
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 .
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 .
It is inferred from these functional assays that an unknown number of protein fragments are produced by contact activation of FXII ( aka autoactivation ) rather than just ALPHAFXIIa and BETAFXIIa as popularly believed .
Kaolin activation of normal , FXI , FIX , FVIII , FVII and protein C-deficient , but not of FXII or prekallikrein ( PKK ) -deficient plasmas led to cleavage of chromogenic substrate for protein C .
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 .
(a) size ( it has a mol wt of approximately 175,000 ) ; (b) synthetic substrate specificity ( D-propyl/phenyl/arginyl-p-nitroanilide is a substrate for the activated forms of Hageman factor , but not the lung protease ) ; (c) antigenic specificity ( an anti-Hageman factor immunoadsorbent column did not remove significant amounts of the lung protease , while it removed most of the activity of activated Hageman factor fragments ) ; and (d) inhibition profile ( the lung proteases was not inhibited by corn trypsin inhibitor ) .
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 .
In both types of activation the FXII zymogen is converted to active enzymes .
(2) PES-SO3Na activated the least FXII no matter which anticoagulant the plasma contained .
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 .
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 .
Possible mechanisms of the contact activation and interaction of the Hageman factor , prekallikrein and high-molecular kininogen in this process are discussed .
Based on these properties ( i.e. 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 .
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 .
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 .
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 .
No activation of the adsorbed FXII was detected .
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 .
The bound PKRN-HK complex prevents the release of generated FXIIa and therefore further binding and activation of FXII from the bulk phase .
It is also noteworthy that bacterial cell wall components themselves , i.e. endotoxin ( or lipopolysaccharide ) of gram negative bacteria and teichoic/lipoteichoic acid of gram positive bacteria , are also able to activate the bradykinin generating cascade-involving activation of Hageman factor as mentioned above .
In this study , the contact system , in which the activation of factor XII and plasma kallikrein is included , is highlighted .
The guinea pig zymogen , in contrast , was cleaved mostly at Arg340-Ile341 ( 70% ) and less abundantly at Gly344-Leu345 ( 30% ) , generating about 85% of the whole potential activity as activated Hageman factor .
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 .
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 Crohns 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 .
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 .
These results provide clear evidence that surface-stimulated BK production , in mice , is dependent on the activation of FXII .
It is the absence of this feedback in Fletcher factor-deficient plasma that accounts for the diminished rate of activation of Hageman factor and therefore a diminished rate of activation of the coagulation and fibrinolytic pathways .
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 ) .
In blood plasma , polyphosphate binds to and alters the biological functions of factor XII , fibrin ( ogen ) , thrombin and factor VII activating protease .
Our data identify polyphosphates as the endogenous factor XII activator in_vivo linking platelet activation ( primary hemostasis ) and fibrin production ( secondary hemostasis ) .
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 ) .
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 .
The gold was modified with both polyethylene glycol ( PEG ) and corn trypsin inhibitor ( CTI ) , a potent and specific inhibitor of activated FXII ( FXIIa ) .
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 principal role is impeding FXII contact with activating surfaces , but this same effect can displace FXIIa from an activating surface into solution where the protease can potentiate subsequent steps of the plasma coagulation cascade .
Endothelial cells produce a substance that inhibits contact activation of coagulation by blocking the activation of Hageman factor .
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 .
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 .
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 .
Their ability to accelerate reciprocal activation of factor XII was investigated by spectrophotometry .
In the presence of HMW-kininogen the rate of activation of factor XII and consequently that of prekallikrein was markedly enhanced .
It is well known that a negatively charged surface activates the contact system , consisting of factor XII , prekallikrein , and high-molecular-weight kininogen .
Association between prothrombin activation fragment ( F12 ) , cerebral ischemia ( S-100beta ) and international normalized ratio ( INR ) in patients with ventricular assisted devices .
In the APTT assay , FXII is activated on a negatively charged surface and proceeds to activate FXI , which activates FIX upon the addition of Ca(2+) .
The prekallikrein activator was identified as Hageman-factor fragments by molecular weight ( 35,000 as estimated by gel chromatography ) , isoelectric point ( 42 to 44 ) , and inhibition by antibody to Hageman factor .
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 .
Structural changes accompanying enzymatic activation of human Hageman factor .
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 .
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 .
Our findings indicate that extracts and secretory products of adult Schistosoma mansoni contain a potent inhibitor of the activation of Hageman factor .
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 .
The other form of activated Hageman factor , beta HFa , leaves the surface , going into solution where it readily activates additional prekallikrein but not factor XI .
Once activated , however , dissociation of kallikrein from the surface allows it to attack adjacent Hageman factor molecules on the same or other particles ; this reaction appears to be more rapid than the rate of Hageman factor autoactivation .
C1INH is the primary inhibitor of the complement proteases C1r and C1s as well as the contact system proteases activated Hageman factor ( coagulation factor XIIa and XIIf ) and plasma kallikrein .
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 .
After conversion of plasminogen proactivator by Hageman factor fragments to the plasminogen activator , the active site of the plasminogen activator is not inhibited by C1INH and is thus readily distinguished from that of kallikrein or PTA .
All proteinases tested activated either clotting factor XII or prothrombin in_vitro , thus resulting in generation of thrombin .
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 .
A 13.6 kDa protein from corn seeds is known to be a highly selective inhibitor of human blood coagulation Factor XIIa ( or activated Hageman factor ) .
This supports the hypothesis that binding to endothelial cells protects the activated FXII against inactivation by its major endogenous inhibitor .
This increase is due , in part , to Hageman Factor activation followed by down-line cascade system activation .
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 .
Under our experimental conditions , the adsorption and activation of FXII on fibrinogen and fibrin seems to be an important mechanism for triggering coagulation .
Using patient blood samples and isolated proteins , we identified a novel class of Factor XII activators .
The results obtained provided an indirect evidence for the existence of a functional relationship between the kallikreine and plasmin systems of the blood at the level of the initial step of their activation , i.e. the Hageman factor .
Inactive kallikrein was activated by an activator containing the Hageman factor and kininogen .
While Ca ( II ) did not replace Zn ( II ) as an activator it significantly enhanced Zn ( II ) - and P(i) -dependent activation of FXII .
During cardiopulmonary bypass , thrombin is generated , which is thought to be initiated by activation of factor XII on the surface of the bypass equipment .
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 .
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 .
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 .
Amidolytic , procoagulant , and activation-suppressing proteins produced by contact activation of blood factor XII in buffer solution .
The plasma kallikrein-HMW kininogen-kinin-system , which besides forming kinin acts decisively in Hageman Factor activation , clotting and fibrinolysis ; 2 .
In_vitro studies of plasma treated with thrombin , plasmin , and contact activating agents indicated that abnormal CIE patterns and increased PKA antigen levels were indicative of activation of the Hageman factor dependent pathway and not the result of plasma clotting by thrombin .
Key initiators of the intrinsic pathway of blood coagulation , the contact activation complex , ( Kallikrein , Factor XII , and high molecular weight Kininogen ) have previously been identified on NPs surfaces .
The conversion of the plasminogen proactivator to plasminogen activator by activated Hageman factor or its fragments has been recognized as an essential step in the conversion of plasminogen to plasmin .
At timed intervals prothrombin activation fragment 1.2 ( F12 ) levels ( thrombin generation ) were measured using an ELISA technique .
While the mechanism of the effect of activated Hageman factor upon C1 activation remains obscure , it is apparent that some intermediate steps , possibly involving a kinin-forming system of plasma , may play a role .
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 .
Activation of bovine factor VII by hageman factor fragments .
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 .
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 .
Enhancements of vascular permeability and edema formation which result from the activation of kinin generating cascade such as Hageman factor by the proteases. ( II ) .
Finally , aggregated proteins have been shown to activate the bradykinin-forming pathway by catalyzing factor XII autoactivation .
The conversion of plasma prekallikrein to kallikrein by the activated FXII and in response to numerous different stimuli leads to the generation of bradykinin ( BK ) and activated HK ( HKa , an antiangiogenic peptide ) .
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 .
Mechanistically , factor XI may be activated by factor XII following contact activation or by thrombin in a feedback activation loop .
Competitive-protein adsorption in contact activation of blood factor XII .
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 .
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 .
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 .
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 .
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 .
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 .
Activation of the classical pathway of complement by Hageman factor fragment .
We have compared the cleavage of purified human Hageman factor ( HF ) by an activated form of human Hageman factor ( HFa ) ( autodigestion ) and by kallikrein .
The time course of HFa and HFf formation indicates that the rate of activation of Hageman factor by kallikrein is much faster than the rate of autoactivation ; the addition of high molecular weight kininogen increases the rate of HFa and HFf formation as well as the extent of HG digestion .
In the cultured HUVEC supernatants , the addition of MaCL increased activated factor VII and prothrombin-fragment 1 + 2 , did not modify UPA , and decreased activated factor XII and differentiating 2 chain UPA , in comparison with samples with control immunoglobulin M added .
In colorectal cancer patients high plasma fibrinogen , FVIII and FIX levels might represent further risk factors for venous thrombotic complications in the immediate post-surgery period , while decreased FVII and FXII concentrations may be an index of intravascular coagulation activation , still in a subclinical phase .
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 .
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 .
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 .
It was shown that the activated Hageman factor and its active fragment convert a greater amount of prekallikrein into kallikrein than is observed under the effects of trypsin and kallikrein .
Thrombin activates fXI , and several studies suggest that fXI promotes coagulation independent of fXII .
Recent studies have revealed that microbial and human cell proteinases activate Hageman factor and/or prekallikrein , or directly release kinin from kininogens .
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 .
Although the Hageman factor-dependent pathways appear to be initiated by contact activation of Hageman factor , the kallikrein generated activates more Hageman factor ; this feedback is necessary for the Hageman factor-dependent pathways to proceed at a normal rate .
Questions have been raised about the role of HMWK in the activation of Hageman factor by surfaces .
Mutation or deletion of SBE- ( -272/-269 ) substantially reduced TGF-beta1-mediated activation of the FXII promoter .
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 .
Thus , factor B of the properdin system is activatable by factor D only when bound to the activated third component of complement , and C3b fragment ; similarly C2 is activated and forms the C3 converting complex , C42 , only when bound to C4b prior to its cleavage by C1 ; C5 can be activated by either of the two convertases only when bound to surface-fixed C3b ; and the mutural activation of Hageman factor and pre-kallikrein on surfaces proceeds efficiently only when HMW-kininogen is present which complexes with pre-kallikrein and possibly with Hageman factor .
Isolation of bovine platelet cationic proteins which inhibit the surface-mediated activation of factor XII and prekallikrein .
Microscopic examination of the large vessels in these test groups showed endothelial damage which indicates a possible source for a plasminogen activator release , or lead to action of Hageman factor and activated plasma plasminogen proactivator .
It is possible that the Hageman factor is activated to modulate the inflammatory response differently in E than in NE .
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 .
We show that activated platelets release inorganic polyphosphate ( polyP ) , a polymer of 60-100 phosphate residues that directly bound to and activated the plasma protease factor XII .
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 .
Similar prekallikrein values were found in serum samples , activated or not , with an excess of Hageman factor and HMWK , which suggests that the decrease of prekallikrein in liver disease is not influenced by the simultaneous decrease of Hageman factor and HMWK .
Recent studies have provided new insight into the molecular structure and functional features of FXI and have demonstrated distinct structural and biological differences between activated factor XII ( FXIIa ) -mediated FXI activation and tissue factor/thrombin-mediated FXI activation .
Coagulation factor XIIa ( activated Hageman factor ) inhibitor from adult Schistosoma mansoni .
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 .
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 .
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 .
It has been found that negative surfaces and amyloids , such as ABETA fibrils , can activate FXII .
C1 inhibitor ( C1INH ) , the major plasma inhibitor of activated C1 , kallikrein , and activated Hageman factor , may be an important factor in limiting inflammatory injury mediated by the complement and contact systems .
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 .
Procoagulant activity of surface-immobilized coagulation factor XIIa ( activated Hageman factor ) is reported .
In contrast to their interactions with other proteinases , which are blocked by normal C1(-) -inhibitor , Type II C1(-) -inhibitors from plasmas of affected members of eight different kindred with this form of hereditary angioneurotic edema all inhibited the specific coagulant activity of activated Hageman factor to some degree .
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 .
APC-SR was inversely correlated ( p < 001 ) with factor VIII and fibrinogen in patients and with prothrombin activation fragment 1.2 ( F12 ) in controls .
Extensive investigations did not reveal any abnormality apart from an elevated activated partial thromboplastin time as a result of factor XII deficiency .
In addition , FXIa can activate factor FXII , which could contribute to thrombin generation through FXIIa-mediated FXI activation .
Accordingly , some polyp-containing pathogens may have evolved strategies to exploit polyP-initiated FXII activation for virulence , and selective inhibition of FXII may improve the host response to pathogens .
This occurred despite the absence of detectable activation of Hageman factor as evidenced by stability of plasma concentrations of prekallikrein in systems anticoagulated with heparin or citrate and despite our inability to detect thromboplastin-like properties in isolated leukocytes .
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 ) .
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 .
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 .
However , on the controls , most of the FXII was in activated form , whereas on the CBAS and Corline surfaces very little activation occurred .
Significant positive associations with BMI were seen for factor VIIc , activated factor XII , antithrombin activity , protein C activity and plasminogen activator inhibitor-1 activity .
In the in_vivo study the enhancement of vascular permeability in guinea pig skin and its sensitivity to inhibitors of activated Hageman factor , plasma kallikrein , or a kininase were examined .
Inositolphospholipid-accelerated activation of prekallikrein by activated factor XII and its inhibition by beta 2-glycoprotein I .
The data show that activated Hageman factor may cause release of kinin by proteolytic cleavage of high Mr kininogen .
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 ) .
Antithrombin III inhibition of activated Hageman factor is augmented by heparin which is also an activator of Hageman factor .
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 .
The 56K protease , which requires zinc ion for activity , was found to possess plasma kallikrein-like properties in_vitro as judged by (i) preferential amidolysis of carbobenzoxy-Phe-Arg-4-methylcoumaryl-7-amide and Pro-Phe-Arg-4-methylcoumaryl-7-amide , which are known substrates for plasma kallikrein ; ( ii ) release of kinin from high-molecular-weight kininogen ; and ( iii ) prompt activation of Hageman factor followed by generation of kallikrein from plasma prekallikrein .
These results imply that zinc ions induce a conformational change in factor XII that makes it a better substrate for its enzyme activators .
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 .
At physiological concentration ( 50 microgram/ml ) , alpha 2PI inhibited the clot-promoting and prekallikrein-activating activity of Hageman factor fragments , the amidolytic , kininogenase , and clot-promoting activities of plasma kallikrein , and the clot-promoting properties of activated plasma thromboplastin antecedent ( PTA , Factor XIa ) and thrombin .
In 1991 it was demonstrated that , besides factor XII , thrombin is capable of activating factor XI in_vitro .
Treatment of human lung fibroblasts with TGF-beta1 resulted in a time-dependent increase in FXII production , activation of p44/42 , p38 , JNK , and Akt , and phosphorylation and translocation into the nucleus of Smad3 .
These results suggest increased activation of both FVII and FXII in hyperlipidaemic subjects , which correlates with increased thrombin generation .
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 .
Here , we review our studies of the last 5 years that led to the identification of the endogenous factor XII activator .
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 .
We failed to detect ICs or IC formation by studying Hageman factor activation and platelet aggregation or by using a very sensitive radio-assay of ICs .
Cold-promoted activation of prorenin was less than or equal to 1% in plasma deficient in factor XII or prekallikrein .
We recently have identified platelet polyphosphate ( an inorganic polymer ) and mast cell heparin as in_vivo FXII activators with implications on the initiation of thrombosis and edema during hypersensitivity reactions .
In patients with hereditary angioedema , kallikrein and bradykinin formation can occur without invoking factor XII activation , although the kallikrein formed can rapidly activate factor XII if it is surface bound .
A far more rapid activation of the remaining unactivated factor XII occurs by enzymatic cleavage by kallikrein ( kallikrein-feedback ) and sequential cleavage yields two forms of activated factor XII ; namely , factor XIIa followed by factor XII fragment ( factor XIIf ) .
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 .
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 .
Increased plasma levels of activated factor FXII ( FXIIa ) are associated with increased risk of atherosclerosis and coronary heart disease .
These bacterial proteases have a number of biological activities , such as degradation of tissue constituents and host defense-oriented proteins , as well as activation of zymogens ( Hageman factor , prekallikrein and pro-matrix metalloproteinases ) through limited proteolysis .
Recent experimental evidence supports a vascular insult through the activation of Factor XII pathways as the initial event .
The role of kallikrein as an enzymatic activator of Hageman factor in fluid-phase was emphasized , and the description of this effect , brought about by a feedback mechanism was given .
Furthermore , the permeability activity of the protease , but not the amidolytic activity , was inhibited by soybean trypsin inhibitor , a well-known inhibitor of plasma kallikrein , as well as by corn trypsin inhibitor , the best inhibitor of activated Hageman factor .
Both forms of amyloid precursor proteins inhibited ellagic acid-induced activation of Hageman factor but did not inhibit activated Hageman factor .
A large number of negatively charged macromolecules , including DNA , glycosaminoglycans , and proteoglycans , were tested as possible activators of the contact ( Hageman factor ) system in_vitro .
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 .
Mice with reduced PKK had ∼ 3-fold higher plasma levels of fXII , and reduced levels of fXIIa-serpin complexes , consistent with fXII being a substrate for activated PKK in_vivo .
Both schistosome extracts and secretory products inhibited the activation of purified Hageman factor by more than 95% .
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 .
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 .
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 .
Of particular interest to these studies , heparin proteoglycan and glycosaminoglycan from rat peritoneal mast cells , and squid chondroitin sulfate E , which is representative of the glycosaminoglycan from cultured mouse bone marrow derived mast cells , induced the reciprocal activation between Hageman factor and prekallikrein .
We developed three methods based on chromogenic substrates to assay the distinct functions of FXII , namely its autoactivation on a negatively charged surface , activation by kallikrein cleavage and the prekallikrein cleavage activity of FXIIa .
Assay method of high molecular weight ( HMW ) kininogen was established by conversion of HMW-kininogen to bradykinin through activation of Hageman factor by glass powder and that of low molecular weight ( LMW ) kininogen was also by treatment of HMW-kininogen-depleted plasma in the same way as that for total kininogen .
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 .
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 : .
These results are consistent with the results of recent in_vitro experiments in which activation of the purified Hageman factor but not of prekallikrein by the 56K protease was elucidated ( Matsumoto et al. , J .
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 .
In addition , HRG inhibits autoactivation of factor XII and factor XIIa-mediated activation of factor XI .
The endogenous and exogenous activating system of blood clotting and possible reasons for lower bleedings with factor XII deficiency. 2 .
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 .
In the presence of Ni(2+) -bearing liposomes , K(m) and k ( cat ) values derived for autoactivation of FXII and prekallikrein , as well as for activation of FXII by kallikrein or prekallikrein by FXIIa , were similar to literature values obtained in the presence of dextran sulfate .
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 .
The correlation with PTT might point to an activation of Hageman factor , which may activate both intrinsic coagulation and ELP release .
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 .
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 .
Investigators have long searched for physiologic activators of FXII and its role in_vivo .
Recent investigations have shown that there is a physiologic pathway for assembly and activation of this system independent of factor XII .
Rat follicular thyroid PCCL3 cells cultivated in Hams F-12 supplemented with 5% calf serum and hormones were exposed to the AMPK pharmacological activator 5-aminoimidazole-4 carboxamide ribonucleoside ( AICAR ) or AMPK antagonist compound C for 24 hours either in the presence or absence of TSH .
Fucosylated chondroitin sulfate , but not sulfated fucan , activates factor XII .
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 .
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 .
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 .
Immunothrombosis is critically supported by neutrophil elastase and the activator molecules of blood coagulation tissue factor and factor XII .
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 .
The appearance of the latter seemed to correspond chronologically to the generation of activated Hageman factor .
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 generation of C1 esterase activity in siliconed plasma obtained from individuals with hereditary angioneurotic edema in remission tends to occur spontaneously , but can be hastened during its incubation with preparations of activated Hageman factor .
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 .
We found that platelets release polyphosphates , linear inorganic polymers of 60-100 phosphate residues that directly bound to and activated factor XII .
These directions include studies suggesting that activation of the intrinsic coagulation cascade through contact activation of factor XII , and the resultant thrombin generation is a pathologic event that leads to undesirable consequences .
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 .
Incubation of Kallikrein , high-molecular weight kininogen , and Hageman factor together , so that activation of all three proteins occurred , did not results in the generation of detectable chemotactic activity .
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 .
Family study showed that her sister with prolonged activated partial thromboplastin time at 83.8 s and FXII activity less than 0.5% was also compound heterozygous for the mutations .
In contrast , we did not find any evidence of contact activation , because markers of activation of prekallikrein and FXII remained undetectable .
Partial identification of the Zn2+-binding sites in factor XII and its activation derivatives .
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 ) .
Initiation of contact activation may involve proteolytic activation of surface-bound Hageman factor by a number of different proteases .
This aptamer functions as a potent anticoagulant by inhibiting the autoactivation of FXII , as well as inhibiting intrinsic pathway activation ( FXI activation ) .
We found that single-stranded aptamers did not have a negative influence on platelets , complement , or inflammation but were able to activate factor XII , kallikrein , and prothrombin in a concentration-dependent manner .
Endotoxin , released from the bacteria , crosses the alveolar wall where it activates pulmonary intravascular macrophages , endothelium , neutrophils , lymphocytes , platelets , complement , and Hageman factor leading to complex interactions of cells and mediators .
Substances biologically similar to plasma kallikrein ( KK ) , a Hageman factor activator , have been shown to be released by basophils in the course of an IgE-dependent reaction .
The system is largely impervious to the level of activated Factor XII , given that a trace ( non-zero ) level is present .
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 .
Conditions for obtaining optimal amounts of free kallikrein with respect to concentration of dextran sulfate , activation time , inhibitors ( C-1-inactivator ) , and requirement of factor XII have been determined .
The amino acid sequence of a corn inhibitor for trypsin and activated Hageman Factor ( Factor XIIa ) was determined by automated Edman degradation from the intact inhibitor and two fragments generated by specific cleavage of the inhibitor .
In order to enhance the activation of factor XII on a surface the HMW-kininogen molecule had to be intact .
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 .
The data indicate that during the coagulation of plasma in the presence of sulfatides , FXI is activated by a mechanism that is thrombin dependent and does not require FXII .
Recent studies suggest that therapeutic blockade of activation of FXII can be of benefit in certain clinical conditions .
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 .
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 .
The uptake and activation of FXII from blood plasma was studied in small-diameter polyethylene tubing , surface-modified by end-point immobilization of heparin .
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 .
Swelling in HAE and production of bradykinin are localized ( and may then disseminate ) ; activation along the endothelial cell surface involves cell membrane ligands of factor XII and high-molecular-weight kininogen , release of endothelial cell heat shock protein 90 , activation of the high-molecular-weight kininogen-prekallikrein complex , and endothelial cell activation at the B2 receptor .
Inhibition of thrombin and activated Hageman factor ( factor XIIa ) was observed with a molar excess of inhibitor .
By kaolin-cephalin , the activation of Hageman factor was weak and slow in deficient plasma during the ten min of incubation .
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 .
It inhibits the autoactivation of Factor XII , the ability of Factor XIIa to activate prekallikrein and Factor XI , the activation of high molecular weight kininogen ( HK ) by kallikrein , and the feedback activation of Factor XII by kallikrein .
We conclude that , during anaphylaxis , basophils may release a protease that is capable of cleaving and activating Hageman Factor , thus providing a mechanism for initiating the in_vivo activation of the Hageman Factor dependent systems .
Our observations in the infected monkeys have led us to conclude that (1) pneumococcal capsular polysaccharide ( PCP ) , immune complexes and complement may not have primary roles in the initiation of DIC ; (2) intact pneumococci may be catalysts for the development of DIC ; (3) the initial event in DIC may be activation of Hageman factor ; and (4) evidence of activation of Hageman factor-dependent systems is present regardless of severity of infection .
We then showed that the alkaline phase of acid activation occurred normally in plasminogen-free plasma but was almost completely absent in plasmas deficient in either Hageman factor or prekallikrein ; alkaline phase activation was restored to these latter plasmas when equal parts were mixed together .
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 .
This study describes a novel biologic surface for FXII activation and activity , which initiates inflammatory events independent of hemostasis .
They did not all form complexes with activated Hageman factor that were stable during sodium dodecyl sulfate-polyacrylamide gel electrophoresis .
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 .
Fibrin formation involves an activation of the coagulation cascade either through the intrinsic pathway , Hageman factor being activated by the altered glomerular basement membrane , either by the extrinsic pathway , infiltrating monocytes and glomerular cells exhibiting a procoagulant activity i.e. thromboplastin or tissue factor .
Amino acid sequence and secondary structural analysis of the corn inhibitor of trypsin and activated Hageman Factor .
Incubation of protoporphyrin with purified Factor XII resulted in activation as measured by amidolysis of a chromogenic substrate .
We analyzed the interaction between PAI-1 and the three serine proteases generated during contact activation of plasma , activated factor XII ( FXIIa ) , FXIa , and kallikrein , and evaluated their effects on fibrinolysis in-vitro .
Simultaneously with the shortening of the ELT an activation of factor XII and of kallikrein was observed .
Activation of the bradykinin-forming pathway can be initiated at the cell surface by gC1qR-induced autoactivation of Factor XII or direct activation of the prekallikrein-HK complex by endothelial cell-derived heat-shock protein 90 ( HSP 90 ) or prolylcarboxypeptidase with recruitment or Factor XII by the kallikrein produced .
The present study may explain that Hageman factor fragments , activated by C1s , promotes kinin generation via kalikrein activation .
Plasma prekallikrein : ~@~ quantitative determination by direct activation with Hageman factor fragment ( beta-XIIa ) .
The lung prekallikrein activator differs from the known physiologic activators of prekallikrein ( the activated forms of Hageman factor ) with respect to :
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 .
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 .
Factor VII is readily converted to factor VIIa by factor XIIa ( activated Hageman factor ) employing an enzyme to substrate weight ratio of 1 : 50 .
Extracts of bioptic samples obtained from ulcerous zones as well as the extracts of leukocytes were shown to activate prekallikrein and Hageman factor in human blood plasma .
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 .
Thus , the inhibitory properties of platelet factor 4 directed against the activation of Hageman factor were confirmed in a purified system .
Whilst the plasma levels of many clotting factors including fibrinogen , FVII , FVIII , FXII , FXIII b-subunit are elevated , the fibrinolytic system is relatively inhibited as a consequence of an increase in plasminogen activator inhibitor type-1 ( PAI-1 ) levels .
Effect of heparin on the inactivation rate of human activated factor XII by antithrombin III .
In contrast , activation of purified FXII in a plasma-free system with respect to supernatant activity indicated significant differences between the materials .
Here , we studied in detail the mechanism underlying the activation of factor XII by MoAb F1 using purified proteins .
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 .
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 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 .
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 ) .
The plasminogen proactivator has been completely separated from prekallikrein and pre-PTA , two other proenzyme substrates of activated Hageman factor or its fragments .
Highly purified bovine plasma prekallikrein was rapidly activated to kallikrein [EC 34218] by bovine activated Hageman factor , trypsin [EC 34214] and Pronase P ( proteinases from Streptomyces griseus ) and more gradually by papain [EC 34222] and ficin [EC 34223] .
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 .
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 .
Prothrombin activation was measured by prothrombin fragment 1.2 ( F12 ) formation .
Human plasma prekallikrein . ~@~ Studies of its activation by activated factor XII and of its inactivation by diisopropyl phosphofluoridate .
By complement activation and generation of biologically active C split products via the classical and the alternative pathway , by interaction with Fc and complement receptors resulting in exocytosis of lysosomal contents including degradative enzymes , cationic proteins , vasoactive amines and mediators effective on lymphocytes and macrophages ; by direct and indirect activation of the Hageman factor followed by stimulation of the kinin , coagulation and fibrinolysis system ; and by modulation of the immune response via the afferent and the efferent branch .
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 .
We have shown that this HAE has a defect in bradykinin overproduction whether the factor XII mutation is present or not , that patients C1 INH is capable of inhibiting factor XIIa and kallikrein ( and not just activated C1 ) but the functional level is approximately 40-60% of normal , and that ALPHA2 macroglobulin protein levels are normal .
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 .
This study demonstrates that prekallikrein and high-molecular-weight kininogen are physically associated in plasma as a noncovalently linked complex and may therefore be adsorbed together during surface activation of Hageman factor .
Functional analyses revealed that PK6 does not interfere with prekallikrein activation by activated Hageman factor ( beta-F XIIa ) , and has no effect on the kininogenase function of activated kallikrein .
Influence of operative trauma on factor XII and inhibitor of plasminogen activator .
Anthracis required secreted zinc metalloprotease InhA1 , which activated prothrombin and factor X directly ( not via factor XII or tissue factor pathways ) .
Diisopropyl fluorophosphate treatment of plasminogen did not inhibit its activation by Hageman factor .
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 .
The two-chain 82,000 dalton form of activated Hageman factor ( alpha-HF(a) ) also cleaved kaolin - bound single-chain Hageman factor in a dose-dependent manner , yielding fragments of 28,000 and , 50,000 dahons under reducing conditions .
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 ) .
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 .
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 .
Seven women were found to have reduced FXII activity ( 19 2-461% ) and prolonged activated partial thromboplastin time ( 33 3-513 s ) .
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 .
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 .
Control of human coagulation by recombinant serine proteases . ~@~ Blood clotting is activated by recombinant factor XII deleted of five regulatory domains .
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 .
Contact activation was demonstrated by the presence of plasma kallikrein ( KK ) activity and activated Hageman factor ( FXIIa ) and/or KK in complex with C1 inhibitor ( C1inh ) , detected by chromogenic peptide substrates or radioimmunoassays , using monoclonal antibodies directed to neodeterminants exposed on complexed C1inh , respectively .
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 .
Stimulation of glycoprotein VI signaling via LAT and PLCgamma2 to form procoagulant platelets ; and activation of factor XII to stimulate thrombin generation and potentiate the formation of platelet-fibrin thrombi .
At least part of this activation is potentiated by the contact activation phase of plasma coagulation , in particular activated factor XII .
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 .
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 .
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 .
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 .
Activated partial thromboplastin time , prothrombin fragment 1.2 ( F12 ) , thrombin antithrombin III complex and D-dimer were measured before , during and after the infusion .
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 .
Trabeculae as collagen bundles in the subarachnoid space were considered to have a possible role in activating the Hageman factor of the coagulation system in SAH .
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 .
Activation of a plasma fraction containing unactivated Hageman factor and prekallikrein followed by chromatography of this fraction on DEAE-cellulose revealed four peaks having bradykinin-generating activity .
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 .
Furthermore , anophensin interacts with both the N-terminus of FXII and domain D5 of HK , which are the binding domains for biological activating surfaces .
Results of this study strongly suggest that activator surface-area dependence observed in contact activation of plasma coagulation does not solely arise at the FXII activation step of the intrinsic pathway .
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 .
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 .
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 .
In addition to its role in coagulation , polyP-induced Factor XII activation mediates the release of the inflammatory mediator bradykinin by activating the kallikrein-kinin system .
Aeruginosa alkaline proteinase , showed a negligible Hageman factor activation .
Changes in the structure of Hageman factor accompanying activation have been examined in this study by circular dichroism spectroscopy .
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 .
HMW kininogen does not affect the binding of Hageman factor to surfaces , but it enhances the function of surface-bound Hageman factor as assessed by its ability to activate prekallikrein and Factor XI .
These large molecular weight basophil derived mediators may , through the activation of the Hageman factor dependent pathways , influence mechanisms which participate in both acute and chronic cell-mediated inflammatory processes .
Moreover , baboons , mice , and rabbits , pretreated with antibodies that selectively inhibit factor XII activation , procoagulant factor XIIa activity , or all enzymatic activities of factor XIIa show significantly reduced propensity for occlusive thrombus propagation in various models of acute thrombogenesis on vascular grafts , membrane oxygenators , and even on injured arteries .
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 .
Prothrombin time ( PT ) , activated partial thromboplastin time ( aPTT ) , thrombin time ( TT ) , fibrinogen ( Fbg ) , factor (F) II , FV , FVII , FVIII , FIX , FX , FXI , FXII , protein C ( PC ) , protein S ( PS ) , antithrombin III ( ATIII ) and ADAMTS13 levels were assessed at Days 0-5 , respectively .
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 .
Resistance to activated protein C , acquired Factor XII deficiency resulting in suppression of intrinsic fibrinolytic activity , activation of endothelial cells through the nuclear factor kappaB pathway leading to tissue factor upregulation , adhesion molecule and cytokine expression and activation of platelets .
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% ) .
Activated partial thromboplastin time ( APTT ) , prothrombin time ( PT ) , International Normalized Ratio ( INR ) , Thrombin time ( TT ) , coagulation factors FI , FII , FV , FVIII , FIX , FX , FXI , FXII , vWF Ag , inhibitors of coagulation ( protein C& S ) and d-dimer were measured .
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 .
Albicans proteinase was observed , and the reaction was inhibited by corn trypsin inhibitor , an inhibitor of activated Hageman factor , and soybean trypsin inhibitor , a well-known inhibitor of plasma kallikrein .
Using different coagulation assays , it was shown that platelet contribution to whole blood coagulation was unrelated to the generation of activated FXII in_vitro .
In contrast , significant changes in coagulation activation markers ( prothrombin fragments F12 , thrombin-antithrombin III complex , and fibrin monomers ) were found only in group 3 .
Reconstituted collagen is not capable of activating factor XII but causes intrinsic coagulation by activating platelets .
This factor seems to interfere , in_vitro process , at the level of glass activation , and after the activation of Hageman factor .
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 .
The ability of HMW kininogen to potentiate the Hageman factor fragments ( HFf ) activation of prekallikrein and Factor XI in plasma was studied .
Our goal was to determine whether these reactions are demonstrable in plasma and distinguish them from activation through factor XII .
The molar ratio of the protein cofactor to factor XII for optimal activation was found to be approximately 1 : 1 .
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 .
However , the activities of fibrinogen and FIX , FXI , and FXII , and plasminogen activator inhibitor-1 ( PAI-1 ) activities were increased in the obese co-twins ( P < 005 ) and strongly correlated with the measures of adiposity , inflammation , and insulin resistance ( r = 032-073 , P < 005 ) among the twin individuals .
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 .
Activations of contact factors were not parallely occurred with the marked consumption of FXII .
Thus , the plasma level of activated FXII ( XIIa ) might represent vascular lesions or be a marker of abnormal lipid metabolism .
By contrast , FXIIa activity is detected spontaneously following FXII activation by a hydrophilic surface and requires no adsorption displacement .
The antiheparin agent hexadimethrine bromide , in concentrations of 20 to 200 mug/ml. , inhibited the activation by active Hageman factor of the plasma enzyme which releases kinin from substrate .
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 Hams F-12 and one part Iscoves modified Dulbeccos medium supplemented with sodium bicarbonate , bovine crystalline insulin , human transferrin , 2-mercaptoethanol , and bovine serum albumin .
Differences between serum and plasma complement , which now is called as the cold activation of complement , was investigated in relation with the phenomenon reported as the cold promoted activation of factor VII , to which kallikrein and Hageman factor are known to participate .
This critical controlling protein has a major inhibitory effect on C1 , kallikrein , activated factor XII of the intrinsic coagulation system , and on plasmin .
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 ) .
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 increase is neither due to an excess of Hageman factor or of an activator , nor to the decrease of an inhibitor .
The enzyme ( with BAEE as a substrate ) was identified as serine proteinase of the trypsin-like type which activated Hageman factor ( the XII factor of clotting system ) and demonstrated the kininogenase activity .
There was no consistent activation of isolated Hageman factor by immunologic reactants as determined by conversion of prekallikrein to its enzymatic form or by shortening of the clotting time of factor XII-deficient plasma .
Inhibition was presumably related to neutralization of the negative charge of activators of Hageman factor .
We here describe the IgE-mediated secretion of large molecular weight mediators which have the potential for the activation of the Hageman factor dependent pathways , and the generation of biologically active peptides .
Among a variety of foreign surfaces , amylose sulfate and sulfatide were the most efficient in the activation reaction of Factor XII and prekallikrein .
The site of action of the kininogen appears to be after that of activated Hageman factor and kallikrein in the generation of clot-promoting activity through activation of plasma thromboplastin antecedent ( PTA ) .
Most biologic surfaces that activate FXII become expressed in disease states .
All the solutions studied did not affect the purified preparations of prekallikrein , but some of them activated partially purified preparations of Hageman factor .
The endothelial lining in segments of the human saphenous vein harvested before and shortly after systemic heparinization of patients was investigated with regard to the ability to inhibit activated FXII .
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 .
Thus , endothelial cell-dependent activation can be initiated by activation of factor XII or by activation of PK-HK .
Past PM exposure was never associated with activated partial thromboplastin time ( aPTT ) , prothrombin time ( PT ) , or factor (F) VII , FVIII , FXII or D-dimers .
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 .
Activation of prekallikrein appears to occur via the active form of Hageman factor .
The activation and function of surface-bound Hageman factor in human plasma are dependent upon both high molecular weight ( HMW ) kininogen and prekallikrein .
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 .
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 ) .
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 .
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 .
Intravenous injection of ellagic acid ( EA , 30 mg/Kg ) , an activator of the Hageman factor , induced congestion of lymph nodes and dilatation of the spleen in rats .
Cleaved high-M(r) kininogen , activated factor XII and plasmin-antiplasmin complexes were measured in ascitic fluid and plasma .
Duration of a vascular permeability reaction caused by an intradermal injection of activated Hageman factor was prolonged in all of these guinea pigs approximately twice as long as the control , indicating a presence of negative feedback regulation of the Hageman factor-dependent kinin generation cascade in dermal tissue via the circulating protease inhibitor .
These results suggest that the contact activation of endogenous Hageman factor could result in the generation of vasoactive opioid peptides derived from circulating large molecular weight precursors .
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 .
The target mentioned above may either be an inhibition of FXII activation or an inhibition of its proteolytic activity .
The active fragment of the Hageman factor was obtained by contact activation of the latter followed by repeated disc-electrophoresis .
Bradykinin ( BK ) is released directly from kininogens or through activation of either Hageman factor or subsequent plasma prekallikrein .
P(i) and Zn ( II ) ions promoted activation of FXII alone ( but not prekallikrein ) and the kinetics of this reaction suggested autoactivation .
This finding indicates that during exposure of CPA-positive plasma samples to low temperatures , Hageman factor fragments , which are inhibited only by C-1 inactivator , induce the activation of the kallikrein system and blood clotting factor VII .
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 .
The conversion of plasminogen to plasmin and the subsequent cleavage of Hageman factor by plasmin to form activators of prekallikrein represents one pathway in which coagulation , fibrinolysis , and inflammation are linked .
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 .
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 ) 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 .
The effect of beta 2-glycoprotein I on the dextran sulfate and sulfatide activation of the contact system ( Hageman factor system ) in the blood coagulation .
Schistosome extracts inhibited activation of Hageman factor both by ellagic acid and by bovine sulfatides .
Surface-energy dependent contact activation of blood factor XII .
Nonenzymatic cell-derived initiators , such as heat shock protein 90 , can activate the HK-PK complex to generate kallikrein , bradykinin , and cleaved HK , even in the absence of Factor XII .
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 ) microg FEU/L .
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 .
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 .
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 .
On both surfaces activation of bound FXII with ellagic acid resulted in consumption of the proenzyme and in inhibition of formed FXIIa .
Whereas most histamine is released during the first half hour , significantly elevated levels of activated Hageman factor and kallikrein complexes with C1 inactivator are seen in antigen-challenged sites between 4 and 6 hr .
It is established that the anaphylactic activation of Hageman factor as well as the aggregation of platelets are not mediated by immune complexes , therefore , other explanations must be found .
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 ) .
Ellagic acid , a known activator of factor XII , produced similar alterations as obtained in anaphylactic shcok .
Protease substrates containing penta-peptides which mimicked the sequence of the cleavage sites from P3 to P2 of guinea pig Hageman factor ( HF ) and PK were synthesized , and kinetic analyses of the hydrolysis by guinea pig activated HF ( HFa ) and kallikrein were carried out .
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 .
We conclude that activation of FXII increases thrombin generation , which promotes TAFIa-mediated attenuation of fibrinolysis .
(3) The rates of activation of prekallikrein by Factor XII and by Factor XIIa were approximately the same at higher concentration of prekallikrein .
TAME esterase activity was absent when Hageman factor - or prekallikrein-deficient plasmas were similarly assayed and prorenin was not activated .
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 .
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 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 .
Tropolone-treated rabbits did not require exogenous stimulation of alpha-adrenergic receptor sites by norepinephrine to localize thrombi in the glomerular capillaries when Hageman factor was activated by ellagic acid and fibrinolysis inhibited by epsilon-amino-caproic acid .
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 .
Binding of negatively charged macromolecules to factor XII induces a conformational change such that it becomes a substrate for trace amounts of activated factor present in plasma ( less than 001% ) .
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 ) .
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 .
We therefore investigated whether an anticoagulant antibody ( 14E11 ) that selectively inhibits prothrombotic FXI activation by activated FXII ( FXIIa ) modifies the course of bowel perforation-induced peritoneal sepsis in mice .
A mechanism of writhing reaction induced by kaolin , a known activator of factor XII , was studied .
(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 .
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 .
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 .
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 .
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 ability of the two forms of activated Hageman factor ( HFa ) produced during contact activation of plasma to activate prekallikrein and factor XI was studied .
Metabolic parameters and parameters of the hemostatic system , such as tissue factor ( TF ) , TF pathway inhibitor ( TFPI ) , plasminogen activator inhibitor-1 ( PAI-1 ) and prothrombinfragment 1.2 ( F12 ) , were determined .
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 .
Change of endothelial cell morphology and exposure of extracellular matrix , increase adhesiveness to leukocytes , decrease production of nitrous oxide , vasoconstriction with some agents , factor XII activation , increase in the release of kallikrein , bradykinin , histamine , serotonin , and leukotriene B4 , and variable effects of platelet activation and aggregation .
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 .
Only limited data exist on changes in activated Factor XII ( XIIa ) levels following mechanical revascularisation , such as percutaneous coronary intervention ( PCI ) .
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the four zymogens after activation by Hageman factor fragment and reduction gave an Mr = 53,000 H-chain and two L-chains , LI ( Mr = 40,000 ) and LII ( Mr = 37,000 ) .
The kallikrein substrate H-D-Pro-Phe-Arg-p-nitroanilide was used in a direct spectrophotometric assay for activated Hageman factor ( HF ) .
Number and cellular origin , expression of tissue factor ( TF ) and phosphatidylserine on MPs , and platelet and coagulation activation markers [beta-thromboglobulin ( beta-TG ) , prothrombin fragment f1.2 ( f12 ) ] were measured in venous blood and in blood from a vascular injury ( shed blood ) by flow cytometry and immunoassays , respectively .
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 .
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 .
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 .
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 .
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 .
The activity of VPF is not inhibited by coinjection of conditioned medium with soybean trypsin inhibitor ; or hexadimethrine ( both known antagonists of tissue plasminogen activator , Hageman factor , and serum kallikrein ) ; or aprotinin ( an antagonist of both plasmin and tissue kallikrein ) ; or phenylmethanesulfonyl fluoride ( a serine esterase ( elastase ) inhibitor ) ; or pepstatin-A ( an acid protease inhibitor which inactivates vascular permeability-inducing leukokinins ) .
Its activation requires the availability of phospholipid and of activated factor XII ( factor XIIa ) , or factor XIa .
Common variants of large effect in F12 , KNG1 , and HRG are associated with activated partial thromboplastin time .
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 ) .
No differences were found in tissue-type plasminogen activator antigen , plasmin-plasmin inhibitor complexes , fibrinogen , D-dimer and activated factor XII values .
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] .
In_vitro activation of the contact ( Hageman factor ) system of plasma by heparin and chondroitin sulfate E .
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 .
High affinity binding of factor XIIa to an electronegative surface controls the rates of factor XII and prekallikrein activation in_vitro .
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 ) .
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 .
Activated thromboplastin time ( APTT ) , factor VII , factor VIII , factor XII , fibrinogen , prothrombin , total antithrombin , normalized activated protein C ( n-APC-sr ) , protein C , protein S , and free protein S .
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 .
C1(-) -inhibitor ( C1(-) -INH ) proteins from normal persons and members of eight different kindred with dysfunctional C1(-) -INH proteins associated with hereditary angioneurotic edema ( HANE ) were compared with respect to their inhibitory activity against purified preparations of C1s- , plasma kallikrein , activated forms of Hageman factor , and plasmin .
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 ) .
Sympathetic activation with anticipatory stress best explained increased baseline activity in FVIII and FXII at week one .
No significant change in sedimentation behavior was noted when the Hageman factor in plasma deficient in plasma thromboplastin antecedent was activated .
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 .
The removal of antithrombin resulted in extensive activation of FXII , whereas the depletion of C1 esterase inhibitor had only a minor effect .
Immobilized Ni(2+) and Cu(2+) bind FXII , FXI and HK with high affinity and stimulate activation of the contact pathway , driving FXII-mediated coagulation .
No direct chemotactic response was detectable for kallikrein , activated Hageman factor , high-molecular weight kininogen , or intact C5 .
It appears that patients with polycythemia vera have chronic activation of the coagulation system , probably initiated by activation of factor XII .
Human lung mast cells and human peripheral basophils were purified and examined for their content of proteolytic enzymes similar to lung Hageman factor activator ( LHFA ) previously found to be released from chopped human lung by an IgE-mediated mechanism .
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 .
Thus , in the rat only those inflammatory reactions involving kinins , presumably generated by Hageman factor activators , are potentiated by ramipril and presumably by other ACE-inhibitors .
Kallikrein is a known endogenous activator of Hageman factor .
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 .
Lactic acidosis can activate C5 from the complement system and factor XII from the contact system directly , even in the absence of cellular components .
All three enzymes initiated prorenin activation ; 50% activation was achieved with Hageman factor fragments at 1 microgram/ml , plasma kallikrein at 2-4 microgram/ml , or plasmin at 5-10 microgram/ml .
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 .
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 .
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 .
It has been suggested that contact with subendothelial tissue provides an alternative biological surface for FXII activation .
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 .
It is concluded that the site of PbAc(2) sensitization to endotoxin is in the blood , and most probably at the level of Hageman factor activation .
The mechanism of complement activation remains unclear , since it is not influenced by EDTA , aprotinin , steroids , or by specific sera depleted of prekallikrein , Hageman factor , C2 , and gamma-globulins .
Thus cryoactivation of prorenin is accompanied by , and may depend upon , the activation of FXII and prekallikrein , supporting other evidence in favour of this hypothesis .
In_vitro tests showed an increase of fibrinolysis by activation of the endogenous pathway via factor XII and prekallikrein .
These findings are consistent with the hypothesis that , in the initial phase of contact activation , high-molecular-weight kininogen links both Factor XI and prekallikrein to the exposed surface where they are activated by surface-bound activated Hageman factor .
These findings are compatible with the concept that single-chain Hageman factor and alpha - HF(a) , are both capable of cleaving and activating kaolin-bound Hageman factor and that a close molecular association of kaolin-bound Hageman factor molecules is required for this reaction .
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 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 .
Both cuprophane ( CUP ) and PAN membranes were able to activate Hageman factor and convert prekallikrein to kallikrein as measured by an ELISA against kallikrein-C1-inactivator complexes .
Overall , the results are consistent with a model in which factor XII undergoes conformational changes upon binding to the activating surface .
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 .
The finding of similar FXIIa levels among patients in either acute or chronic phases of coronary atherosclerosis suggests that the initial arterial denudation and the acute-phase response associated to acute coronary syndromes are not major determinants for prolonged FXII activation .
Additionally , elevated levels of plasminogen activator inhibitor-1 , factor (F) VII , FXII , fibrinogen and tissue plasminogen activator occur with insulin resistance to create an atherothrombotic risk cluster .
Next , we determined the potential to form enzyme-inhibitory complexes after complete in_vitro activation of the plasma samples with a FXII trigger .
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 .
Measurements of activated FVII ( FVIIa ) , FVII zymogen , and activated FXII ( FXIIa ) concentrations made after the low-fat and high-oleate meals showed a significant increase in FVIIa only after the high-oleate meal .
A time course for the generation of activated FXII using purified FXII solution at physiologic concentrations on two similar negatively charged polymers was performed .
This may be one mechanism for Hageman factor activation in_vivo .
Therefore , a complete evaluation of all these properties of FXII and FXIIa has to be considered when formulating a strategy for blocking FXII activation .
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 .
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 ) .
Similarity in adsorption properties further undermines the idea that FXII and/or FXIIa are distinguished from other blood proteins by unusual adsorption properties resulting in chemically-specific interactions with activating anionic surfaces .
The pretreatment plasma contained primarily ( 94% ) dysfunctional C1INH that did not inactivate or complex with either purified C1s , activated Hageman factor , or kallikrein and small amounts ( 6% ) of functionally normal C1INH .
To identify this enzyme we first tested the ability of Hageman factor fragments , plasma kallikrein ( EC 34218 ) , and plasmin ( EC 34217 ) to activate prorenin in acid-treated plasma .
Surface contact activation is a complex phenomenon involving negatively charged surfaces , FXII , high molecular weight kininogen and plasma kallikrein .
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 .
The mechanisms by which human high molecular weight kininogen ( HMKrK ) contributes to the surface-dependent activation of the Hageman factor systems have been studied .
Factor XI complexed with antibody did not bind to high molecular weight kininogen or undergo activation and cleavage by two-chain Factor XII .
Bismuth subgallate , which is an insoluble analog of ellagic acid , lost its ability to activate Hageman factor on being exposed to BAC770 .
A recently described HAE with normal C1 INH ( based on inhibition of activated C1s ) presents similarly ; the defect is not yet clear , however one-third of patients have a mutant factor XII gene .
Yet stoichiometric activation of PK-HK to yield kallikrein in the absence of factor XII can be initiated by heat shock protein 90 ( HSP-90 ) which forms a zinc-dependent trimolecular complex by binding to HK .
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 chamber fluids were sampled over a 6-hr period for histamine and activated Hageman factor and plasma kallikrein which were complexed to C1 inhibitor .
The main conclusions are that Zn2+ is required to initiate contact activation , modulating factor XII for autoactivation .
It aggregated rat platelets and , as a consequence , activated Hageman factor in in_vitro , as well as in_vivo , conditions .
It is further suggested that activation of such kallikrein by the antigen-antibody reaction proceeds through Hageman factor .
These two different reaction processes are considered to be linked by the release of plasminogen activator and/or Hageman factor activating enzyme .
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 .
C1 inhibitor deficiency causes dysregulation of the plasma bradykinin-forming cascade with overproduction of bradykinin due to uninhibited effects of activated factor XII and plasma kallikrein .
As mAb F1 can also induce this conformational change , this antibody may provide a unique tool in studies of the activation of factor XII .
Contact activation system proteins ( e.g. , Factor XII , kallikrein ) have been implicated as direct or indirect activators of plasminogen .
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 .
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 .
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 .
No comparable activity was observed when equimolar concentrations of either the native Hageman factor ( HF ) or two-chain activated form of Hageman factor ( HFa ) were incubated with serum .
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 .
The initial conversion of prekallikrein to kallikrein by the surface-bound Hageman factor in the presence of HMW kininogen is followed by a rapid enzymatic activation of Hageman factor by kallikrein .
The activation of prekallikrein by Hageman factor under initial-rate conditions occurs after a lag and is prevented by an inhibitor of Hageman factor from corn .
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 .
Amidolysis caused by kaolin activated human normal plasma was independent of coagulation factors II , X , XI , and protein C , but dependent on prekallikrein and to some extent on factor XII .
In this article we thereby analyze the prevalence , as well as the pathogenesis , of thrombosis associated with apparently paradoxical triggers such as during factor replacement therapy in haemophiliacs or in patients with von Willebrand disease ; in patients with inherited clotting factor deficiencies especially involving factor XII , factor VII , fibrinogen ; or in those with a prolonged activated partial thromboplastin time for the presence of lupus anticoagulant .
The aim of this analysis was to assess the predictive value of activated factor XII type A ( XIIaA ) and B-type natriuretic peptide ( BNP ) in acute coronary syndrome patients stratified according to troponin release and to evaluate their complementary utility as predictors of all-cause mortality and recurrent troponin T ( TnT ) -positive events .
Tests of haemostasis documented a slightly prolonged activated partial thromboplastin time ( APTT ) ( 45 ) due to mild factor XII deficiency ( clotting activity 32% ) .
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 .
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 .
Because collagen also induces plasma clotting by activation of factor XII , we evaluated the effects of aegyptin on collagen-induced coagulation activation and how it interferes with thrombosis in three different in_vivo models .
These results suggest that substances classically known as """"activating surfaces"""" promote the activation of Hageman factor indirectly by altering its structure such that it is much more susceptible to proteolytic activation by other plasma or cellular proteases .
Lethal shock did not occur in alpha 2M-depleted animals even at an elastase dose of 0.2 mg/kg when Hageman factor was simultaneously depleted , indicating that elastase induces shock through activation of the Hageman factor-dependent system .
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 .
Since contact activation of blood does not play a demonstrable role in normal hemostasis , and there has been no evidence generated to date suggesting that activation of factor XII has a physiologic function , current research now supports the original concept , developed over 2 decades ago , that temporal pharmacologic inhibition of thrombin generation through the contact pathway may have therapeutic potential and could produce beneficial antithrombotic activities without hemostasis impairment.
Activation of the kinin forming system could be mediated via injury , trauma , coagulation pathways ( Hageman factor and thrombin ) and immune complexes .
These studies show that the functional defect of prekallikrein Zurich is due to an impaired cleavage by activated factor XII and probably the lack of enzymatic activity of the cleaved variant molecule .
Here we found that an inhibitor of activated FXII , corn trypsin inhibitor , and anti-FXII , anti-kallikrein and anti-FXI Abs inhibited HSV1-initiated clotting .
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 .
FXII-deficient mice are resistant to ferric chloride-induced arterial thrombosis , and this resistance can be reversed by infusion of human fXII. 9A2 partially blocks , and 15H8 completely blocks , the prothrombotic effect of fXII in this model. 15H8 prolonged the activated partial thromboplastin time of baboon and human plasmas. 15H8 reduced fibrin formation in collagen-coated vascular grafts inserted into arteriovenous shunts in baboons , and reduced fibrin and platelet accumulation downstream of the graft .
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 .
In a purified system , long polyP significantly enhanced the rate of FXII and prekallikrein activation and the activation of FXI by thrombin but not by FXIIa .
Markers of PLT activation ( CD62P and CD63 expression and soluble CD62P ) and coagulation activation ( activated FXII and prothrombin fragment 1 + 2 [F1 + 2] ) , RBC microvesicles , blood gases , and residual WBCs were measured .
Collagen activation of platelet-associated Factor XI has been proposed as a mechanism for initiating intrinsic clotting independent of Factor XII .
These bacteria , upon isolation , activated Hageman factor .
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 .
Although many initiating triggers have been discussed , the most potent might be a bacterial endotoxin which activates Hageman factor or some components of serum complement .
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 .
Therefore , tryptase neither activates nor destroys human Hageman Factor .
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 .
These data indicate that although the titer of Hageman factor strongly influences the cold activation of factor VII , other factors may affect these phenomena .
Negatively charged surfaces may activate Factor XII and the prekallikrein-kinin cascade , resulting in bradykinin ( BK ) production .
Five human monoclonal IgG with small differences in their sequences were tested for binding to protein C , activated protein C , plasmin , factor VIIa ( FVIIa ) , FIX , FIXa , and FXII .
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 .
Esterification of collagen , which neutralizes 80-90% of the free carboxyl groups , reduced coagulant activity by over 90% and it is suggested that the free carboxyl groups of glutamic and aspartic acids provide the negatively charged sites critical for Hageman factor activation .
The conversion of plasminogen proactivator to plasminogen activator by Hageman factor fragments results in the generation of chemotactic activity for human neutrophils .
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 .
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 .
Thus , bismuth subgallate , a particulate activator of Hageman factor , was no longer effective after it had been exposed to eosinophil cationic protein .
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 .
The phylogenetic and functional relationships between HGFA and FXII as well as urokinase and tissue-type plasminogen activator are discussed .
Another C1(-) -INH ( Za ) had almost seven times as much inhibitory activity as normal C1(-) -INH against activated Hageman factor , but had decreased activity against C1s - and no activity against plasmin .
The corn inhibitor of activated Hageman factor : purification and properties of two recombinant forms of the protein .
Cultured rabbit endothelial cells , therefore , possess the capacity to activate Hageman factor by proteolysis .
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 ) .
1 ) Serratia marcescens 56- , 60- , and 73-kDa proteinases , Pseudomonas aeruginosa alkaline proteinase and elastase , and Aspergillus melleus proteinase ( this group activated Hageman factor but not prekallikrein ) ; 2 ) Vibrio vulnificus proteinase , subtilisin from Bacillus subtilis , and thermolysin from Bacillus stearothermophilus ( this group activated both Hageman factor and prekallikrein ) ; 3 ) Streptomyces caespitosus proteinase and V8 proteinase from Staphylococcus aureus ( this group activated neither Hageman factor nor prekallikrein , but generated kinin from high molecular weight kininogen directly ) .
The activation of plasma prekallikrein by single-chain factor XII has been studied in the presence of high molecular weight kininogen and kaolin .
The pseudomonal elastase cleaved 22-24% of the human molecule at Arg353-Val354 , and the remainder at Gly357-Leu358 resulting in the generation of about 20% of potential activity as activated Hageman factor , compared with trypsin activation , while it hydrolyzed Arg340-Ile341 bond in guinea pig molecule and generated about 75% of activity as activated Hageman factor .
Here , we show that fibrillar type I collagen provoked a dose-dependent shortening of the clotting time of human plasma via activation of factor XII .
We screened for antibodies against activated factor XII ( FXIIa ) using phage display and demonstrated that recombinant fully human antibody 3F7 binds into the FXIIa enzymatic pocket. 3F7 interfered with FXIIa-mediated coagulation , abolished thrombus formation under flow , and blocked experimental thrombosis in mice and rabbits .
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 ) .
Ratnoff and his coworkers recognised that factor XII ( XII ) stimulates cell growth and activates mitogen-activated protein kinase .
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 .
Furthermore , soy bean trypsin inhibitor ( SBTI ) but not corn trypsin inhibitor ( CTI ) abrogated CD62P exposure , suggesting that thrombin was derived via FX but not FXII activation .
Furthermore , both fCSs significantly activated factor XII , which has been proved to be associated with adverse clinical events associated with heparin contaminated by oversulfated chondroitin sulfate .
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 .
The triggering effect of endotoxin could be reproduced by ellagic acid , a known activator of factor XII .
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 .
Our investigations on platelet and coagulation indicate that aspirin prevents disseminated intravascular coagulation through an interference with the blood coagulation and Hageman factor activation rather than by the inhibition of platelet aggregation and availability of platelet procoagulant activity .
We herein report that , like plasma kallikrein , preparations rich in this basophil protease also activate human Hageman Factor by proteolytic cleavage of the zymogen molecule into light and heavy chains .
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 .
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 .
The data permit supposing that optimal activation of the Hageman factor requires the polar ( but not ionic ) groups with hydrophilic properties on activating surfaces .
This study indicates that heparinized plasma does not support activation of the contact system mediated through activation of factor XII .
The Cl inhibitor , which inactivates Cls is the major plasma inhibitor of activated Hageman factor and kallikrein .
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 .
Mechanisms of activation of the classical pathway of complement by Hageman factor fragment .
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 .
Neurotropin also inhibited the binding of FXII and HK to the activating surface .
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 .
Theoretically , formation of kallikrein by this factor XII-independent route can activate surface-bound factor XII to generate factor XIIa resulting in a marked increase in the rate of bradykinin formation as stoichiometric reactions are replaced by Michaelis-Menton , enzyme-substrate , kinetics .
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 .
These experiments exhibited enzymatic activation of Hageman factor and prekallikrein using """"liberator"""" , obtained after incubation of the leukocyte fraction enriched with basophils and specific allergen .
Compensatory changes in plasma levels of factor XII procoagulant activity , activated protein C and of alpha 2-antiplasmin were not observed .
Reviewed here is the molecular mechanism of contact activation of the Hageman factor pathways and discussed in the interaction of Hageman factor with the negatively charged surface , prekallikrein , factor XI and high MW kininogen .
Preincubation of lipopolysaccharides ( LPS ) of Bacteroides fragilis , Bacteroides vulgatus , and Fusobacterium mortiferum with purified human Hageman factor ( HF ) followed by addition of purified human prekallikrein resulted in the activation of HF , as measured by the generation of kallikrein using the tripeptide substrate N-alpha-benzoyl-L-proline-L-phenylalanine-L-arginine-4-nitroanilide .
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 .
Therefore , the clot-promoting activity of activated Hageman factor might be relatively unimpaired if Hageman factor fragments are also present .
Surface and fluid phase activities of two forms of activated Hageman factor produced during contact activation of plasma .
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 .
This heparin-binding domain may block the activation of Hageman factor by negatively charged agents .
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 ) .
Guinea pig macroalbumin which is a major circulating inhibitor of activated Hageman factor was immunologically depleted from three animals .
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 .
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 .
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 .
This protease appears to be unrelated to any known activator of Hageman factor by molecular weight and inhibition profile and was shown to be distinct from an IgE-dependent prekallikrein activator , as well as the kininogenase activity defined as basophil kallikrein of anaphylaxis .
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 ) .
A serine protease in human plasma termed hyaluronan-binding protease HABP is structurally related to plasminogen-activators , coagulation FXII and hepathocyte growth factor activator .
Inhibition was not specific for ellagic acid-induced activation of Hageman factor , as inhibition was also observed with sulfatide-induced activation .
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 ) .
Modulation of the human monocyte binding site for monomeric immunoglobulin G by activated Hageman factor .
Interaction of trypsin , beta-factor XIIa , and plasma kallikrein with a trypsin inhibitor isolated from barley seeds : a comparison with the corn inhibitor of activated Hageman factor .
Finally , we show that our nanobody-based assays in_vitro distinguish various activation products of FXII that differ with the type of activator present :
A certain optimal mixture of purified Hageman factor , HMrK , prekallikrein , and kaolin gave the same rapid initial rate of activation of purified factor XI as an equivalent aliquot of factor XI-deficient plasma .
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 ) .
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 ) .
The activation rate of prekallikrein by pseudomonal elastase in Hageman factor deficient plasma was remarkably improved when the plasma was reconstituted with purified Hageman factor molecule .
To elucidate potential mechanisms of these anaphylactic reactions , whether dialysis membranes can activate the Hageman factor-dependent ( contact ) pathways as assessed by the in_vitro generation of activated Hageman factor ( Hfa ) , as well as the formation of kallikrein and subsequent bradykinin generation was examined .
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 :
In contrast , heparin and activated mast cells induced excessive edema in mice deficient in the major inhibitor of factor XII , C1 esterase inhibitor .
Catecholamines may interact with the ALPHA2-adrenergic receptors located on platelets and convert factor XII to XIIa or through the kallikrein-kinin system , they may activate factor XII .
For the in_vitro study , activation of purified Hageman factor ( HF ) and PK was examined by using cancer cell lines and virus-transformed cells that produced plasminogen activator ( PA ) at a high rate .
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 .
To further elucidate the role of the amino terminal binding site in the regulation of FXII activation , we have characterized a FXII recombinant protein ( rFXII-triangle up19 ) deleted of the amino acid residues 3-19 , which are encoded by the second exon of FXII gene .
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 .
Infection superimposed on a traumatized host increases the total host protease load even more by additional activation of Hageman Factor and cascade systems .
Thus , reciprocal activation is the predominant mode of factor XII activation in normal plasma .
CaINH was the only factor active upon the Hageman factor fragments functioning at the initial step of the fibrinolytic pathway , alpha2M was the only factor active against the plasminogen activator and the most active inhibitor of plasmin .
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 .
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 .
Of the common plasma prekallikrein activators , mesothelial cells expressed HSP90 , but not prolylcarboxypeptidase or Factor XII .
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 .
Amino acid sequence of the heavy chain of human alpha-factor XIIa ( activated Hageman factor ) .
In_vitro activation of the contact activation system ( Hageman factor system ) in plasma by acidic phospholipids and the inhibitory effect of beta 2-glycoprotein I on this activation .
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 .
Activation of bovine factor VII ( proconvertin ) by factor XIIa ( activated Hageman factor ) .
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 .
The OSCS associated adverse reactions were attributed to activation of the contact system via the plasma mediator , activated factor XII ( FXIIa ) , which triggers kallikrein ( KK ) activity .
Human coagulation factor XI has been purified , and upon activation with Hageman factor fragments , was found to convert the fibrinolytic proenzyme plasminogen to plasmin .
These results strongly suggested a pathological role of elastase in pseudomonal sepsis through activation of the Hageman factor dependent pathway .
[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 .
The result suggests that diminished levels of Hageman factor that may be seen associated with IgE-dependent reactions can be due to digestion and depletion rather than activation , and other criteria for activation of the contact system must be employed .
Trasylol was less effective in blocking this effect of activated Hageman factor .
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 .
Isolated CAC promoted the generation of activated Factor XI ( XIa ) in a mixture containing purified Factor XI , Factor XII , and kaolin .
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 .
The activation of the coagulation and fibrinolytic systems and platelet activation were evaluated at 6 different time points before , during , and after the operation , measuring prothrombin fragment 1.2 ( F12 ) , plasmin-antiplasmin complex , and platelet factor 4 , respectively .
Moreover , individuals with the F12 -4T allele also had less thrombin generation ( assessed by endogenous thrombin potential , thrombin peak and time to achieve the peak of thrombin ) using a test with low tissue factor concentration and explicit contact phase activation .
Activation and function of human Hageman factor . ~@~ The role of high molecular weight kininogen and prekallikrein .
Tryptase from human mast cells does not activate purified human Hageman factor .
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 .
It is concluded that the sharp control mechanism that gives rise to bolus-production of FIIa from the intrinsic pathway must occur between surface activation of FXII and the FII --> FIIa step , is not related to inhibition by FIIa , and does not involve deactivation of procoagulant surfaces .
PolyP secreted from platelets leads via activation of Factor XII to in_vivo thrombin and fibrin formation .
By contrast , the three components of the kinin-forming system ( Hageman factor , prekallikrein , high-molecular-weight kininogen ) were not activated by Candida sp .
It is suggested that systemic heparinzation of patients may both activate endothelial bound FXII and interfere in the inhibition of formed FXIIa by depriving the endothelium of required amounts of antithrombin .
The dissemination of contact activation of plasma was examined by measuring the cleavage of Hageman factor ( HF ) molecules on two separate sets of kaolin particles , one of which contained all of the components of the contact activation system , HF , prekallikrein ( PK ) and high molecular weight kininogen ( HMWK ) in whole normal plasma , and the second set of particles containing only HF and HMWK , being prepared with PK-deficient plasma .
New investigations indicate that there is a proteolytic pathway on cells for PK activation independent of FXII .
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 .
Activation of these two pathways was unexpectedly linked and dependent on fluid-phase activation 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 .
Acidic polysaccharide in the pollen that adsorbed to the diethylaminoethyl ( DEAE ) column was the causative agent of factor XII activation .
In addition , the combined results of this and previously reported data from this laboratory indicate that the reciprocal activation of Hageman factor by kallikrein in fluid phase is essential for normal rate of activation of the intrinsic-clotting , kinin-forming , and fibrinolytic systems .
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 .
These findings indicate that (1) catheters are prothrombotic because they trigger fXII activation , and (2) fondaparinux does not prevent catheter-induced clotting unless supplemented with low-dose heparin or bivalirudin .
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 .
The author describes the method of assessment of the C1-inhibitor , the principle being activation of plasma prekallikrein by Hageman factor fragment ( HFf ) to the active enzyme kallikrein which splits the specific chromogenic substrate NO-Pro-Phe-Arg-pNA .
We then found that , although plasma kallikrein could activate prorenin in plasma deficient in either Hageman factor or prekallikrein , Hageman factor fragments were unable to activate prorenin in prekallikrein-deficient plasma .
We evaluated each subjects 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 .
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 .
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 .
The altered sedimentation behavior of purified activated Hageman factor probably reflects its decreased solubility in aqueous media .
Their procoagulant properties were due to their effects on the activation of Hageman factor ( XII ) while the anticoagulant effect was mainly directed towards fibrinogen .
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 .
Kallikrein was greater than 10 times more active in its ability to activate Hageman factor than plasmin and Factor XI .
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 .
Effect of kallikrein-kinin system activation by factor XII f pretreatment on experimental hemorrhagic shock .
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 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 .
Our aim was to investigate whether activated FXII ( FXIIa ) is elevated in patients with coronary atherosclerosis , and whether disease status ( acute phase or stable state ) affects circulating levels of FXIIa .
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 .
The prekallikrein and high-molecular-weight kininogen levels were sufficient for activation of factor XII .
Endothelial cells express a matrix protein which binds activated factor XII in a zinc-independent manner .
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 .
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 .
There was no difference in FXII surface activation by silicon dioxide or in kallikrein-like activity with and without activation by dextran sulfate .
Determination of kallikreinogen ( KKN ) in human plasma by activation with Hageman factor fragment ( F XIIf ) .
Thus , an active site appears to be induced in prekallikrein by binding to HK and any of the aforementioned reactions can generate kallikrein prior to factor XII activation by autoactivation of the HK-PK complex .
We performed investigations to examine whether this mechanism was true for FXII activation on endothelial cells ( HUVEC ) .
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 .
Alternatively , soybean trypsin inhibitor abolished the proteolytic activity associated with PK and FXII activation on HUVEC .
Proteolytic cleavage and activation of isolated , single chain , zymogen Hageman factor was observed in the presence of kaolin alone .
Triglyceride-lowering treatment with etofibrate in 10 of these men for 6 weeks increased fasting and postprandial protein C and plasminogen and also slightly decreased the activation of fXII ; however , it did not reverse the postprandial increase of PAP or change the decrease of prothrombin activation fragment1+2 .
The sulfated galactan from A.muscoides , which showed mostly serpin-independent anticoagulant activity and reduced activation of FXII , drastically reduced arterial thrombus formation .
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 .
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 ) .
Plasmatic prekallikrein , C1-inhibitor , alpha 2-macroglobulin , activated partial thromboplastin time , prothrombin time , factor XII , factor XI , factor V and prealbumin were measured .
Through this mechanism they inhibit the autoactivation of factor XII and factor XI , the reciprocal activation of factor XII and prekallikrein , the activation of factor XI by thrombin and factor XIIa , the cleavage of high-molecular-weight kininogen in plasma , and plasma extravasation induced by polyphosphate .
Plasma thrombin markers thrombin-antithrombin complexes ( TAT ) and prothrombin factor 1+2 ( F12 ) plus platelet activation markers soluble CD40 ligand ( sCD40L ) , BETA-thromboglobulin and P-selectin were also measured.48 consecutive patients with severe AS and five with moderate AS , free of angiographically-proven coronary artery disease and clinically overt bleeding , were studied .
In order to analyze the clinical features and laboratory findings in patients with acquired hemophilia A , one case of acquired hemophilia A was studied , the medical history , clinical features , ultrasonography and laboratory examination including activated partial thromboplastin time ( APTT ) , prothrombin time ( PT ) , thrombin time ( TT ) and FVIII : C , FIX : C , FXI : C , FXII : C ratio , as well as medical treatment were analyzed .
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 .
These results suggest a structural alteration of FXII Locarno , affecting the plasma kallikrein cleavage site Arg353-Val354 and thus formation of activated FXII ( alpha-FXIIa ) .
These data provide the first evidence for FXI activation in low-grade endotoxemia and suggest that FXI is activated independently of FXII .
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 .
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 ) .
Activated partial thromboplastin time ( APTT ) , FXII procoagulant activity ( FXII : C ) , FXII antigen ( FXII : Ag ) and other coagulants were measured .
There were no differences in the test values of Factor XII , activated partial thromboplastin time ( APTT ) , or fibrin degradation products ( FDPs ) among whole blood samples exposed to P4HB or PVC and the blank control groups ( P > 05 ) .
These observations suggest that normal contact activation in plasma is associated with proteolytic activation of surfacebound Hageman factor .
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 .
Complement components are activated by immunologic and non-immunologic mechanisms through various plasma protein systems such as immunoglobulins , properdin , plasmin , thrombin and Hageman factor .
Thus cold-promoted activation of prorenin depends on the presence of factor XII and prekallikrein , whereas the other clotting factors are not essential .
A new protein inhibitor of trypsin and activated Hageman factor from pumpkin ( Cucurbita maxima ) seeds .
Western blotting analysis with specific antibodies against various parts of the contact factors revealed that limited activation of FXII is sufficient to promote plasma kallikrein activation , resulting in the conversion of high-molecular-weight kininogen and bradykinin generation .
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 .
Circulating procoagulant microparticles isolated from plasma directly activated factor XII in buffer and in diluted plasma .
These include hypoplasminogenemia , decreases in plasminogen activator , increases in plasminogen activator inhibitor , and Factor XII deficiency .
Radioimmunoassays ( RIAs ) for the detection of C-1-inhibitor ( C-1-Inh ) complexed to either kallikrein or activated Hageman factor ( factor XIIa ) are described .
(b) In fluid phase , activation with kallikrein and plasmin did not result in cleavage of large fragments of rabbit Hageman factor , although the activation required hydrolytic capacity of the enzymes .
These data suggest that (i) FXII binds to HUVEC specifically , saturably , and reversibly in a zinc-dependent manner , ( ii ) HK and FXII may compete with each other for the same cell-surface receptor/s , and ( iii ) cell-bound FXII is capable of undergoing activation to FXIIa .
Whether chloroform activation of plasminogen requires Hageman factor-cofactor was not determined , but glass-adsorbed plasma , containing Hageman factor and plasminogen , did not generate appreciable fibrinolytic or caseinolytic activity .
These findings support the concept that the prothrombotic activity of catheters reflects their capacity to activate fXII and identify CTI immobilization as a novel approach for rendering catheters and other blood-contacting medical devices less thrombogenic .
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 ) .
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 .
Initiation of the cascade upon binding to negatively charged surfaces ( or macromolecules ) is dependent on factor XII autoactivation , conversion of prekallikrein to kallikrein , and a feedback activation of factor XII by kallikrein .
In earlier studies , suspensions of mixed types of granulocytes , other nucleated peripheral blood cells , and platelets inhibited activation of Hageman factor by ellagic acid , glass , and sulfatides .
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 .
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 .
Still proof is lacking that FXII is activated by platelets in a more physiological environment .
The protease could activate proteolytically clotting factor zymogens , including FXII , FXI , FX , and prothrombin , to their functional enzymes in_vitro and plasma milieu .
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 .
Inactivation of plasminogen activator inhibitor type 1 by activated factor XII plays a role in the enhancement of fibrinolysis by contact factors in-vitro .
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 .
Whereas peak levels of histamine were obtained after 1 hr of challenge , both Hageman factor and kallikrein activation , as assessed by complex formation , tended to peak later from the 2nd to the 5th hr .
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 .
Activated platelets may thereby constitute an intravascular locus for contact activation , which may explain the recently reported importance of FXII in thrombus formation .
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 .
Effect of heparin on the activation of factor XII and the contact system in plasma .
This pathway for PK with subsequent FXII activation indicates physiologic activities .
The possibility of an involvement of the kallikrein-kinin system in increasing vascular permeability induced by intradermal injection of the guinea pig activated Hageman factor ( beta HFa ) was examined .
Prolongation of the activated partial thromboplastin time corresponded in every instance with factor XII activities of ≤30 percent .
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 .
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 .
Plasma prothrombin ( PT ) and activated partial thromboplastin time , activities of vWF : RCo , FVII , FVIII , FIX , FXI , FXII , FXIII , fibrinogen and D-dimer concentrations were measured in 54 subjects with and 44 without NAFLD diagnosed by proton magnetic resonance spectroscopy .
This may be associated with Hageman factor activation or release of platelet factor 3 .
Contact activation was determined by measuring FXII activity ( FXIIA ) by a chromogenic substrate assay .
The cleavage and formation of activated human Hageman factor by autodigestion and by kallikrein .
Fibrinolytic activity measured as euglobulin clot lysis time [ECLT] and amidase activities toward chromogenic peptide substrates H-D-Valyl-L-Leucyl-L-Lysine-p-nitroanilide 2 HCl [S-2251] , designed for plasmin determination , H-D-Valyl-L-Phenylalanyl-L-Lysine-p-nitroanilide 2 HCl [S-2390] , designed for the determination of t-PA in plasma via plasminogen activation and H-D-Prolyl-L-Phenyl-Alanyl-L-Arginine-p-nitro-anilide 2 HCl [S-2302] , designed for the determination of kallikrein and activated Hageman factor , increased when 15.7 mmol l-1 concentration of acetone was reached .
Reconstitution experiments showed that hamadarin inhibits activation of the plasma contact system by inhibition of the reciprocal activation of factor XII and kallikrein .
Surfaces which induce kinin formation by activating Hageman factor in plasma ( glass , kaolin , celite , barium carbonate and carboxymethylcellulose ) were inactivated by bathing in aqueous solutions of hexadimethrine .
However , in a very sensitive test for factor XII activation ( contact promoted shortening of the thrombotest ) a slight activation of this factor was observed .
The procedure to obtain a complete activation of FXII has still to be studied .
During CPB significant decreases in FXII levels and significant increases in FXIIa-like and kallikrein-like activities were found indicating activation of the FXII-plasma kallikrein pathway during CPB .
Thus , the plasma kallikrein/kinin system has two mechanisms for its activation : one that is dependent and another independent of factor XII .
We recently generated nanobodies against the catalytic domain of activated FXII ( FXIIa ) .
In addition , cortisone-treated animals did not require exogenous stimulation of alpha-adrenergic receptor sites by norepinephrine to localize thrombi in the glomerular capillaries when Hageman factor was activated ( by ellagic acid ) and fibrinolysis inhibited ( by epsilon-aminocaproic acid ) .
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 .
Asymptomatic identical twins were found to show the prolonged activated partial thromboplastin time , which was corrected by addition of normal , Hageman factor deficient or Fletcher trait plasma but not corrected by Fitzgerald or Williams plasma .
The APTT is based on the principle that in citrated plasma , the addition of a platelet substitute , factor XII activator , and CaCl2 allows for formation of a stable clot .
These highly sulfated chondroitin sulfates activate factor XII in in_vitro assays , based on kallikrein release .
We investigated whether selectively inhibiting FXII-mediated FXI activation , while leaving other FXI and FXII functions intact , could improve the outcome of experimental AIS in mice .
Reported that the normal activation of fibrinolysis by surface contact requires , in addition to Hageman factor and plasminogen , a HF cofactor which is present in the euglobulin fraction and other factors present in the supernatant .
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 .
When prekallikrein is activated endogenously in plasma by the addition of kaolin or Hageman factor fragment , approximately 84% of kallikrein is now bound to C-1 inactivator and 16% to alpha 2-macroglobulin .
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 .
Intrinsic coagulation starts upon blood matrix change , resulting in activation of factor XII ( F XII ) to F XIIa and/or of prekallikrein to kallikrein .
These fragments of 28,000 and 52,000 daltons are similar in size to those produced during activation of Hageman Factor by plasma kallikrein .
Therefore , these findings point to the existence of multiple mechanisms of activation of factor XII .
The contact system is a protease cascade that is initiated by factor XII activation on cardiovascular cells .
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 .
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 .
Perfusion of ellagic acid into nonsensitized lungs will also release kallikrein , presumably through activation of Hageman factor .
During surface-initiated blood coagulation in_vitro , activated factor XII ( fXIIa ) converts factor XI ( fXI ) to fXIa .
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 .
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 .
The above-mentioned substances were individually prepared on polystyrene meshwork squares , and then exposed to a purified FXII solution or non-calcium containing plasma ( citrated and dialyzed normal pooled plasma ) in polystyrene cuvettes coated with surface-immobilized heparin , to completely block contact activation and the coagulation mechanism that might be induced by the cuvette surfaces .
With purified reagents , a process including surface adsorption and activation of FXII occurred within 1 second .
Our data suggest that sulfatides stimulate kallikrein-dependent factor XII activation by two distinct mechanisms :
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 ) .
Plasma levels of activated FVII ( FVIIa ) but not activated FXII ( FXIIa ) are increased in the post-prandial state when there is a transient increase in triglyceride levels .
I ml of the """"liberator"""" containing 10(7) cells activated Hageman factor up to 12-20 mU per min ( evaluated by BAEE-esterase activity of the kallikrein developed ) as well as kallikrein activity was increased up to 80-130 mU within 1.5-2 hrs of incubation .
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 .
The major determinants of thrombin generation ( ETP and peak height ) at 1 pm TF were fibrinogen , FXII ( despite inhibition of contact activation ) , free TFPI and antithrombin ( AT ) , both in the absence and in the presence of TM .
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 ) .
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 .
Lasser has proposed a theory based on the biochemical catastrophies secondary to the damage of the vascular endothelium and the activation of the Hagemans factor XII .
The low molecular weight kininogen and a prekallikrein activator analogous to mammalian factor XII , but treatment with bovine plasma kallikrein generates ornitho-kinin [Thr6 , Leu8] -BK .
Activation of the intrinsic coagulation pathway was evaluated by measurements of factor XII , prekallikrein , and kallikrein inhibitors .
PK is activated by coagulation factor XIIa and then cleaves HK to generate bradykinin and factor XII to generate further XIIa .
Homologous type I and II repeats are known to occur in tissue plasminogen activator , factor XII and a bovine seminal plasma protein .
The multiple forms of activated Hageman factor and their potential biologic significance are also discussed .
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 .
In this study , we evaluate NOs effect on factor XII ( fibrinogen ) adsorption and activation , which causes the initiation of the intrinsic arm of the coagulation cascade .
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 .
Using components purified from human plasma , we have examined the effects of C1 inhibitor ( C1 INH ) , the primary inhibitor of activated Hageman Factor ( HFa ) and Hageman factor fragment ( HFf ) , on Hageman Factor ( HF ) autoactivation .
Estrogen induction and contact phase activation of human factor XII .
Complete correction of prolonged activated partial thromboplastin time on mixing test prompted us to perform factor assays , which revealed a markedly decreased FXII activity ( <05% ; below the detection limit ) .
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 .
They initiate and propagate DVT by interacting with platelets and by the exposure and activation of circulating tissue factor and FXII .
A ) Effects on whole blood coagulation , which is characterized by increased velocity of coagulation , increased firmness of the formed coagulum and prolonged initiation phase of the coagulation ; b ) Genetic regulation of blood cells , which is characterized by increased platelet activation , impaired fibrinolysis and impaired function of the contact activation pathway of coagulation , and c ) Reduced functional activities of single coagulation factors FXII : C , FX : C and FII : C .
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 .
The shortening of the activated partial thromboplastin time test suggested identity of the catalytic activities with that of activated FXII molecules .
Although most coagulation enzymes cannot be measured specifically and accurately , assays for activated factor XII and factor VII have recently become available .
The experiments described demonstrate that this may occur through the activation of Hageman factor by this agent .
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 .
Lysosomal enzymes of neutrophil leukocytes carried out both direct and indirect activation of prostaglandin synthesis via the kinin system , affecting the Hageman factor , which , except of kinins , activated blood coagulation , fibrinolysis and blood complement .
When PKA was assayed after kaolin activation of plasma at 0 degrees using the method developed by Laake & Vennerod ( 1973a & b ) for the determination of PKA ( activated factor XII ) in human plasma , no differences were registered between plasma from rats treated with dextran and plasma obtained from control rats .
Contact activation proteins were analyzed by flow cytometry and FXII , FXI , high-molecular weight kininogen , and prekallikrein were detected on activated platelets .
This suggests that potent , surface-mediated activation of factor XI in plasma is explicable in terms of Hageman factor , HMrK , and prekallikrein .
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 .
Earlier studies have shown that isolated platelets in buffer systems can promote activation of FXII or amplify contact activation , in the presence of a negatively charge substance or material .
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 .
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 .
In the 1960s , a platelet activity that promoted FXII activation was identified but its biochemical nature remained unknown .
Amidolytic properties of single-chain activated Hageman factor .
Collagen types III , IV , and V did not appear to activate Hageman factor under the conditions tested .
In the contact phase of activation of the kinin-forming , intrinsic clotting , and fibrinolytic systems , high-molecular-weight kininogen acts as a cofactor for the activation of Factor XI , prekallikrein , and Hageman factor .
This activation was mediated by factor XII binding to collagen .
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 .
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 .
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 .
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 .
To investigate contact activation reactions , a chromogenic assay was used to measure prekallkrein ( PK ) hydrolysis to kallikrein ( Kal ) by activated factor XII ( FXIIa ) at test hydrophilic ( clean glass ) and hydrophobic ( silanized glass ) surfaces in the presence of bovine serum albumin ( BSA ) .
This chemotactic activity can be distinguished from that generated by Hageman factor activation of prekallikrein and is demonstrable in plasma that is genetically deficient in prekallikrein ( Fletcher factor deficiency ) .
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 .
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 ) .
In a purified system , the activation of FXII and prekallikrein by long polyP promoted FIX activation and prothombin activation .
Corn trypsin inhibitor ( CTI ) has been considered the molecule of choice to inhibit activated factor XII ( FXIIa ) during the conduct of experimentation focusing on tissue factor-initiated coagulation .
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 .
Endotoxins from gram-negative bacteria induce the release of tissue factor ( TF ) , Tumor Necrosis Factor ( TNF ) and interleukin-1b ( IL-1b ) , and gram-positive organisms can release bacterial mucopolysaccharides that directly activate factor XII .
Plasma kinin formation after in_vitro activation of factor XII in the coagulation system was examined in 4 patients with hereditary angioneurotic edema .
Chemical modification of histidine and arginine residues does not inhibit the amidolytic activity of activated Hageman factor .
Intratracheal instillation of UFPs resulted in a procoagulant response in WT mice plasma at 20 h , whereas it was entirely suppressed in FXII(-/-) mice. Overall , the data suggest that PM promotes its early procoagulant actions mostly through the TF-driven extrinsic pathway of coagulation , whereas PM-driven long lasting thrombogenic effects are predominantly mediated via formation of activated FXII .
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 .
The delayed coagulation in plasma exposed to the unmodified polystyrene meshwork can be explained by a two-step process : first , adsorption of fibrinogen , and second , activation of FXII .
DIC in these shock patients , accompanied by a decrease in PK , probably was mediated via Factor XII activation .
The data characterize dextran sulfate as a potent in_vivo activator of factor XII with implications for bradykinin-mediated vascular permeability and blood pressure control .
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 .
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 .
VVP was shown to possess the ability to activate the human system through the same mechanism as that clarified in the guinea pig system , namely , VVP converted both human zymogens ( Hageman factor and plasma prekallikrein ) to active enzymes ( activated Hageman factor and plasma kallikrein ) , and the then generated kallikrein liberated bradykinin from high-molecular-weight kininogen .
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 .
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 .
In HAE-C1INH patients the thrombotic risk is not increased even though activation of the contact system is poorly regulated .
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 ) .
Amyloid-BETA ( 1-42 ) protofibrils formed in modified artificial cerebrospinal fluid bind and activate microglia .
These data suggest that the presence of platelets in the CLX storage container partially suppresses coagulation activation at significant cost to platelet viability .
Normal , TAFI-deficient and TAFI-deficient/FXIII-supplemented plasma was exposed to tissue-type plasminogen activator and activated with either celite or TF .
Furthermore , we corroborate previous work indicating that procoagulant surfaces remain activating after repeated use and are not poisoned or denatured in the process of activating plasma coagulation .
Intraarticular activation of the fibrinolytic system has been suspected to occur in patients with arthritis .
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 .
Radial double immunodiffusion experiments using antiserum to C1q , C1r , and C1s on HFf-treated serum demonstrated the dissociation of the C1 trimolecular complex , with concomitant reduction of C1r antigenicity that is indicative of C1 activation .
Inverse associations with BMI were seen for tissue plasminogen activator activity and activated protein C ratio .
The system is activated by an inorganic polymer , polyphosphate that is released from activated platelets .
We then studied the effect of other heparin-like anticoagulants on the thrombin-mediated factor XI activation .
We believe that one of the most efficient ways to prevent pathologic clot formation is simultaneous inhibition of activated factors ХII and ХI.
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 .
The activation procedure is compared to other known procedures .
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 .
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 ) .
Parahaemolyticus , a human pathogen causing primarily watery diarrhea , showed far less ability to activate and to cleave the human zymogens .
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 .
Anaphylactic release of a prekallikrein activator from human lung in_vitro .
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 ) .
A parallel increase in the intrinsic pathway of coagulation may be limited by elevated alpha-1-antitrypsin at the level of activated Factor XI .
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 was shown by an increase in the FVII activity ratio ( 119 +/- 029 vs. 131 +/- 034 ; p = 00000001 ) , FXIIa ( 081 +/- 050 ng/mL vs. 090 +/- 051 ng/mL ; p = 0006 ) , and F1+2 ( 119 +/- 020 nmol/L vs. 124 +/- 020 nmol/L ; p = 0000005 ) after irradiation with 30 Gy , whereas an increase of PAP ( 162 +/- 115 ng/mL vs. 202 +/- 120 ng/mL ; p = 00004 ) demonstrated activation of the fibrinolytic system .
Oxygen depletion may alter the results of radiation sterilization and carcinogen activation .
Both plasmin and kallikrein amplify the inflammatory response by activating components of the contact activation system .
Dissemination of contact activation in plasma by plasma kallikrein .
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 .
Activated protein C reversed the ECLT shortened by Ca(2+) -supplementation ( 863+/-174% ) , but did not affect the ECLT shortened by kaolin ( 314+/-21% ) .
Regardless of the triggers , PK can only be activated on HK bound to the artificial negatively charged or to cell membrane surfaces .
Heparin is unable to prevent contact activation by three different membranes .
Short-term hyperbaric exposure and decompression performed according to current safety standards activates platelets and the fibrinolytic system .
This major cleavage occurred simultaneously with activation .
Persistent activation of coagulation afterstopping infusions in our study suggests that a longer course of antithrombotic treatment may be needed to pacify the thrombus .
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 .
The assembly and activation of the kinin forming system components on human umbilical vein endothelial cells ( HUVEC ) have been studied in great detail .
Additional experiments utilized plasminogen activator inhibitor 1 deficient or alpha2-antiplasmin-deficient plasma .
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 .
On the control of the plasma contact activation system on human endothelium : comparisons with heparin surface .
Activation of the contact system in cerebrospinal fluid of patients with Alzheimer disease .
Thus , HANE attack is considered to be elicited in kindreds with the hereditary disposition by activation of plasma protease systems , particularly by that of kallikrein-kinin system .
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 .
Rabbit prekallikrein . ~@~ Purification , biochemical characterization , and mechanism of activation .
This mystery has led several investigators to search for an """"alternate"""" activation pathway for factor XI .
Activation was assessed by conversion of prekallikrein to kallikrein , as determined by amidolytic assay and by cleavage of 125I-Hageman factor into 52,000 - and 28,000-dalton fragments .
Initiation appears to depend on a trace of intrinsic activity present in HF that is at most 1/4000 that of activated HF ( HFa ) ; alternatively traces of circulating HFa could subserve the same function .
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 .
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 .
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 .
Activation of the plasma clotting , fibrinolytic , and kinin-kallikrein system in preterm infants with severe idiopathic respiratory distress syndrome .
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 .
Our results demonstrate that zinc treatment of RPE cells increases catalase expression and activates the transcription factor Sp1 .
Contact activation of human plasma prorenin in_vitro .
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 .
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 .
In our attempt to find a physiological agonist that activates PAR3 receptors , we screened several coagulation proteases using PAR4 null platelets .
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 activation of pro-UK by platelet-bound kallikrein provides an explanation for the observed platelet mediated promotion of pro-UK-induced clot lysis.
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 .
One potential APTT procofactor activator in this setting is FXIa .
After maximal activation of normal human plasma the esterolytic activity amounts to 16.82 +/- 2.03 mukat/l plasma ( n = 25 ) .
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 .
Activation of the coagulation system in the subarachnoid space after subarachnoid haemorrhage : serial measurement of fibrinopeptide A and bradykinin of cerebrospinal fluid and plasma in patients with subarachnoid haemorrhage .
Activation of intrinsic coagulation pathway in pre-eclampsia .
This deficiency which induces no bleeding tendency is characterized by a considerable lengthening of the activated Partial Thromboplastin Time and an abnormality of the fibrinolysis activation .
Like heparin , ODSH inhibits complement activation , binding to the leukocyte adhesion molecule P-selectin , and the leukocyte cationic granular proteins azurocidin , human leukocyte elastase , and cathepsin G .
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 .
The review summarises the mechanisms that contribute to PK activation and its emerging role in diabetes and metabolism.
Hageman-factor-dependent fibrinolysis : generation of fibrinolytic activity by the interaction of human activated factor XI and plasminogen .
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 .
In clotting whole blood FXIIa-AT and FXIa-AT complexes were specifically formed , demonstrating that AT is a potent inhibitor of FXIIa and FXIa generated by platelet activation .
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 kallikrein system in hyperbetalipoproteinemia .
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 .
This study examined the effect of filtration with three different filters ( MBF1 , MBF2 , and MBF3 ) on MB concentration , residual cells , coagulation factors , and activation measures of coagulation , fibrinolysis , and complement in MB-treated ( 1 microM/L ) plasma units .
Prasugrel , a P2Y12 adenosine diphosphate ( ADP ) receptor antagonist effectively inhibits ADP-mediated platelet activation and aggregation , and may be useful in reducing vaso-occlusive crises in sickle cell disease ( SCD ) .
Thrombin can activate factor XI in the presence of dextran sulfate or sulfatides .
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 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 .
Blood coagulation is a tightly regulated process of sequentially activated serine proteases culminating in fibrin formation , which is critical for limiting posttraumatic blood loss but also may contribute to acute thrombotic diseases , most notably myocardial infarction and stroke .
The lung prekallikrein activator was partially purified by sequential chromatography on sulfopropyl-Sephadex , DEAE-Sephacel , and Sepharose 6B .
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 .
Each molecule of surface-bound , activated HF was calculated to cleave at a minimum , 20 molecules of PK per minute .
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 .
We propose that independent mechanisms for bypass of Factors XII and XI are important in physiologic activation of coagulation .
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 .
Trimix instead of air , decreases the effect of short-term hyperbaric exposures on platelet and fibrinolysis activation .
Targeting polyP with phosphatases interfered with procoagulant activity of activated platelets and blocked platelet-induced thrombosis in mice .
Zinc-dependent contact system activation induces vascular leakage and hypotension in rodents .
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 ) .
These results are compatible with the concept that HF passively crosses the damaged glomerular filter where it may become activated in Bowmans space or in fluid draining damaged glomeruli in this model of nephrotoxic nephritis in the rabbit .
Activated partial thromboplastin time and minor coagulopathies .
Treatment of HF with 10 ( -2 ) M diisopropylfluorophosphate yielded preparations containing 0.2 to 0.9% activated HF as assessed in plastic cuvettes .
In particular , abnormalities of plasminogen , tissue plasminogen activator release and elevated tissue plasminogen activator inhibitor levels seem to be associated with thromboses .
However , the quantitative role of FXIIa as a plasminogen activator in contact activation-dependent fibrinolysis in plasma is still unclear .
It has also been reported that AS is associated with increased activation of blood coagulation .
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 .
The enhancing effect of TF was blocked by hirudin , which indicated thrombin involvement in FXI activation .
The platelet activation by cellulose was assessed by measuring the released serotonin .
Activation of coagulation after administration of tumor necrosis factor to normal subjects .
A comparison of two APTT reagents which use silica activators .
Deficiency of fibrinogen appears to enhance , minimally , activation of the coagulation sequences by test materials .
Activated partial thromboplastin time ( APTT ) is a commonly used coagulation assay that is easy to perform , is affordable , and is therefore performed in most coagulation laboratories , both clinical and research , worldwide .
The activation is inhibited by beta 2-glycoprotein I at physiological concentrations. 4 .
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 .
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 .
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 .
Alpha 2PI had minimal inhibitory effect on surface-bound activated PTA and activated Stuart factor ( Factor Xa ) .
Addition of C1INH after activation led to an increase in levels of FXIIa-C1INH and FXIa-C1INH ( p < 005 ) , which were still lower than in controls ( p < 005 ) , while the levels of kallikrein-C1INH did not change .
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 .
After prolonged treatment with tryptase , proenzymes could be fully activated with their specific activators .
The proteolytic activation pattern of 80,000-dalton rabbit HF was the same as that previously reported for human HF .
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 .
Based on these results , we conclude that plasma Cl(-) -Inh complex levels during sepsis may not properly reflect the extent of contact activation .
A combined deficiency of factor VIII and contact activation defect in a family of cats .
Plasma tissue plasminogen activator ( t-PA ) and released t-PA remained unaffected by r-HuEPO in both groups throughout the study .
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 .
These results suggest that the pathological activation of the kallikrein-kinin system might occur under certain clinical conditions in pseudomonal infections .
We studied the role of elastase-like protease ( ELP ) of human granulocytes in the activation and consumption of clotting factors and their specific inhibitors .
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 .
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 .
The possible involvement of contact system in AD is suggested by the finding that this system is massively activated in CSF of AD patients .
The role of endotoxin immunity , neutrophil degranulation and contact activation in the pathogenesis of post-operative organ dysfunction .
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 .
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 .
To investigate the close association between different antiphospholipid antibodies ( aPL ) caused by infection and their appearance together with a prolonged activated partial thromboplastin time ( aPTT ) .
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 .
The involvement of the high molecular weight rat kininogen in the activation of the rat contact system by kaolin-cephalin , kaolin , sulfatides and ellagic acid has been investigated , using a rat plasma congenitally devoid of this kininogen .
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 .
Furthermore , activation of prekallikrein by kaolin was observed in mouse plasma as amidase activity to produce fluorescence from the synthetic substrate .
The only plausible explanation consistent with current understanding of coagulation-cascade biochemistry is that procoagulant stimulus arising from the activation complex of the intrinsic pathway is dependent on activator surface area .
Activation of the classical complement pathway is initiated by immune complexes consisting of IgM antibody or IgG subclasses 1 , 2 , and 3 .
Contact activation of plasma : structure-activity relationships of human high molecular weight kininogen .
It appears that an acid-induced conformational change of the prorenin molecule is not required for its activation by plasma kallikrein .
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 .
Activation of porcine F .
Dextran sulfate activation of the propositas 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 .
It also inhibited , but to a lesser extent , activated factor X .
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 .
Activated partial thromboplastin time ( APTT ) , F XII procoagulant activity ( F XII : C ) , F XII antigen ( F XII : Ag ) and other coagulant parameters were assayed .
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 .
This phenomenon has been called cold-promoted activation of factor VII ( CPA ) .
HFf-dependent activation was prevented by prior treatment of HFf with the active site-directed inhibitor , H-D-proline-phenylalanine-arginine chloromethyl ketone or with a specific inhibitor of activated HF derived from corn .
Low doses of the platelet activating factor caused a slight decrease in progesterone production .
The addition of purified activated beta-XII led to a complete restoration of fibrinolysis in homozygotes .
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 .
Hypotension associated with prekallikrein activator ( Hageman-factor fragments ) in plasma protein fraction .
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 ) .
By contrast , kinin generation and fibrinolysis resulting from the formation of kallikrein can be initiated either at the site of contact activation , by alpha-HFa action , or throughout the plasma , by beta-HFa ; further dissemination of these activities is assured by the rapid dissociation of kallikrein itself from the surface .
Measuring cell permeability in real-time using electric cell-substrate impedance sensing ( ECIS ) , we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK .
Activation of factor XI by products of prothrombin activation .
Plasminogen activators provide effective treatment for patients with acute myocardial infarction .
The data indicate that forms of thrombin other than ALPHA-thrombin contribute directly to feedback activation of FXI in plasma and suggest that FXIa may provide a link between tissue factor-initiated coagulation and the proteases of the contact system .
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 .
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 .
To investigate the role of activated protein C resistance ( APCR , factor V Leiden ) in coronary artery thrombosis .
In_vivo demonstration in humans that large postprandial triglyceride-rich lipoproteins activate coagulation factor VII through the intrinsic coagulation pathway .
Moreover , our findings indicate the development of nanobodies against activated enzymes offers improved opportunities to investigate their contribution to health and disease.
Blood samples collected by cardiac puncture at this time were tested for the amounts of prekallikrein activator ( PKA ) and kallikrein after acetone - and then kaolin activation of the plasminogen-free plasma .
This may represent a control link between activation of the intrinsic coagulation-kinin pathway and the initiation of the classical complement cascade .
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 .
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 .
[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 ) .
These findings demonstrate activation of the kallikrein-kinin system as a part of pathological plasma proteolysis in multiple trauma patients .
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 .
Kaolin treatment of high-molecular weight ( HMW ) kininogen-deficient plasma yields an even more profound abnormality in the rate of formation of activated HF-C1 INH complexes reflecting the complex role of HMW kininogen in the initiation of contact activation .
Blood flow through the nonendothelialized false lumen is a potential trigger for the activation of the hemostatic system ; however , the physiopathology of the aortic dissection induced coagulopathy has never been precisely studied .
Cell-associated HK is proteolyzed during the course of prekallikrein activation , releasing kallikrein from the surface .
Tight-binding inhibition was observed for activated Stuart factor ( factor Xa ) and plasmin .
These results demonstrate that LPS of selected gram-negative anaerobes activate HF and thereby initiate the intrinsic pathway of coagulatio