Pathophysiology of Haemostasis and Thrombosis
Feedback Mechanisms in Blood Coagulation and Their Inhibition by Heparins
Simulation Model for Thrombin Generation in PlasmaWillems G.M.a · Lindhout T.b · Hermens W.Th.a · Hemker H.C.baCardiovascular Research Institute Maastricht and bDepartment of Biochemistry, University of Limburg, Maastricht, The Netherlands
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Article / Publication Details
Published online: April 24, 2009
Issue release date: 1991
Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0
ISSN: 1424-8832 (Print)
eISSN: 1424-8840 (Online)
For additional information: https://www.karger.com/PHT
Abstract
A simulation model for the production of thrombin in plasma is presented. Values of the reaction rate constants as determined in purified systems are used and the model is tested by comparison of simulations of factor Xa, factor Va and thrombin generation curves with experimental data obtained in thromboplastin-activated plasma. Simulations of the effect of hirudin indicate that factor V is predominantly activated by thrombin and not by factor Xa. The model predicts a threshold value for the factor Xa production which, if exceeded, results in explosive and complete activation of prothrombinase. The dependence of this threshold value on different negative feedback reactions, e.g. the inactivation of thrombin and factor Xa by antithrombin III (+ heparin), is investigated. The threshold value, for control plasma in the range of 1–10 pM total factor Xa production, can be raised two orders of magnitude by accelerated inactivation of factor Xa and prothrombinase but is hardly affected by a tenfold increase in the rate of thrombin inactivation or by increased production of activated protein C. This latter effect, however, results in a more gradual input-response relation between factor Xa input and the extent of prothrombinase activation.
© 1991 S. Karger AG, Basel
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Article / Publication Details
Published online: April 24, 2009
Issue release date: 1991
Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0
ISSN: 1424-8832 (Print)
eISSN: 1424-8840 (Online)
For additional information: https://www.karger.com/PHT
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