Willems1991 - Simulating thrombin generation
Mathematical model of blood coagulation to simulate factor IIa, Va and Xa concentration profiles. Publication also illustrates the effect of hirudin on factor IIa, Va and Xa generation.
- Simulation model for thrombin generation in plasma.
- Willems GM, Lindhout T, Hermens WT, Hemker HC
- Haemostasis , 1/ 1991 , Volume 21 , Issue 4 , pages: 197-207
- Cardiovascular Research Institute Maastricht, The Netherlands.
- 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.
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|Willems1991.cps||Model COPASI file. Attempt to reproduce figure 1. Initial concentrations given in table one for prothrombin (1000nM), factor V (30nM), protein C (100nM) and fibrinogen (10,000 nM). To improve the simulation results the initial concentration of APC was set to 500 nM (anything less than 350nM resulted in factor IIa and Xa plateauing) and APC to 5nM (so that Va returned to zero). Another set of initial condtions was also simulated: Fibrinogen - 1,000nM, ATIII - 100nM, II - 20nM, V - 10nM, APC-10nM, protein C - 10nM.||99.32 KB||Preview | Download|