Factor XI activation in a revised model of blood coagulation

@article{Gailani1991FactorXA,
  title={Factor XI activation in a revised model of blood coagulation},
  author={David Gailani and G J Broze},
  journal={Science},
  year={1991},
  volume={253},
  pages={909 - 912}
}
Coagulation factor XI is activated in vitro by factor XIIa in the presence of high molecular weight kininogen (HMWK) and a negatively charged surface. Factor XII deficiency is not associated with bleeding, which suggests that another mechanism for factor XI activation exists in vivo. A revised model of coagulation is proposed in which factor XI is activated by thrombin. In the absence of cofactors, thrombin is more effective (kcat/Km = 1.6 x 10(5)) than factor XIIa (1.7 x 10(4)) in activating… 
Activation of factor XI in plasma is dependent on factor XII.
TLDR
It is concluded that in plasma surroundings factor XI is not activated byThrombin, and that proposals of thrombin initiation of the intrinsic coagulation cascade are not supportable.
Activated factor V is a cofactor for the activation of factor XI by thrombin in plasma
TLDR
A role for (activated) factor V as a cofactor in the activation of factor XI by thrombin is proposed, which offers insights into the coagulation system in both health and disease.
Role of blood coagulation factor XI in downregulation of fibrinolysis
TLDR
The role of factor XI in hemostasis can be seen as a combination of procoagulant and antifibrinolytic actions and may lead to new strategies for the treatment of thrombotic disorders.
Newer concepts of blood coagulation
TLDR
An in vitro model of blood coagulation reactions that mimics as closely as possible the in vivo condition is described and it is indicated 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 enhancedThrombin generation on the platelet surface.
The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy.
Factor XI contributes to thrombin generation in the absence of factor XII.
TLDR
Using plasma in which fXII is either inhibited or absent, it is shown that fXI contributes to plasma thrombin generation when coagulation is initiated with low concentrations of tissue factor, factor Xa, or alpha-thrombin.
Polyphosphate is a cofactor for the activation of factor XI by thrombin.
TLDR
It is proposed that polyphosphate is a natural cofactor for factor XI activation in plasma that may help explain the role of factor XI in hemostasis and thrombosis.
Thrombin activates factor XI on activated platelets in the absence of factor XII.
TLDR
Thrombin activates enough factor XI to enhance subsequent thrombin generation in a model system that does not contain factor XIIa or nonphysiological cofactors, suggesting that platelet surfaces might provide the site for throm bin activation of functionally significant amounts of factor XI in vivo.
Roles of platelets and factor XI in the initiation of blood coagulation by thrombin.
  • P. Walsh
  • Biology
    Thrombosis and haemostasis
  • 2001
TLDR
To account for the variable hemostatic defect in patients with factor XI (FXI) deficiency, with normal hemostasis in contact factor deficiencies, a coagulation paradigm is presented whereby trace quantities of thrombin activates FXI bound to the platelet surface in the presence of prothrombin or high Mr kininogen.
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References

SHOWING 1-10 OF 28 REFERENCES
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.
TLDR
The results suggest that the activation offactor XI by thrombin and possibly the autoactivation of factor XI proceed in plasma to lead fibrin clot formation and may have a role on an appropriate negatively charged surface in normal hemostasis.
Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation.
  • B. Osterud, S. Rapaport
  • Medicine, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1977
TLDR
Contact of blood with tissue factor represents a second mechanism, bypassing activated Factor XI, for the activation of Factor IX during hemostasis, and may help to explain the discrepancy between the mild bleeding of hereditary Factor XI deficiency and the severe bleeding of genetic Factor IX deficiency.
Mechanisms for the involvement of high molecular weight kininogen in surface-dependent reactions of Hageman factor.
  • J. Griffin, C. Cochrane
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1976
TLDR
The ability of various mixtures of purified human Hageman factor, HMrK, prekallikrein, and kaolin to activate coagulation factor XI was determined with factor XIa (activated factor XI) clotting assays, suggesting that potent, surface-mediated activation of factor XI in plasma is explicable in terms of Hageman factors, H MrK, and prekalikre in.
Activation of human factor IX (Christmas factor).
TLDR
The mechanism of activation of human Factor IX and its inhibition by antithrombin III is essentially identical to that previously shown for bovine Factor IX.
AN ENZYME CASCADE IN THE BLOOD CLOTTING MECHANISM, AND ITS FUNCTION AS A BIOCHEMICAL AMPLIFIER
TLDR
It has been shown that contact activates Factor XII (Hageman factor) perhaps by unfolding its molecule, which leads successively to the activation of Factors XI (PTA) and IX (Christmas factor), and X (Stuart–Prower factor), the evidence suggesting that all these reactions are enzymatic.
Amidolytic assay of human factor XI in plasma: comparison with a coagulant assay and a new rapid radioimmunoassay.
TLDR
A simple, accurate amidolytic assay and a radioimmunoassay have been devised for measuring factor XI in plasma that correlate well with the coagulant activity of factor XI, as determined in the laboratory.
Interactions among Hageman factor, plasma prekallikrein, high molecular weight kininogen, and plasma thromboplastin antecedent.
  • O. Ratnoff, H. Saito
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1979
TLDR
High molecular weight kininogen was needed for expression of Hageman factor's clot-promoting properties and plasma prekallikrein played a minor role in the interaction of ellagic acid-treated Hagemanfactor and plasma thromboplastin antecedent.
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.
TLDR
Observations suggest that normal contact activation in plasma is associated with proteolytic activation of surfacebound Hageman factor.
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