Importance of Initial Concentration of Factor VIII in a Mechanistic Model of In Vitro Coagulation
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This computational study generates a hypothesis for the coagulation protein whose initial concentration greatly influences the course of coagulation. Many clinical malignancies of blood coagulation arise due to abnormal initial concentrations of coagulation factors. Sensitivity analysis of mechanistic models of blood coagulation is a convenient method to assess the effect of such abnormalities. Accordingly, the study presents sensitivity analysis, with respect to initial concentrations, of a recently developed mechanistic model of blood coagulation. Both the model and parameters to which model sensitivity is being analyzed provide newer insights into blood coagulation: the model incorporates distinct equations for plasma-phase and platelet membrane-bound species, and sensitivity to initial concentrations is a new dimension in sensitivity analysis. The results show that model predictions are most uncertain with respect to changes in initial concentration of factor VIII, and this hypothesis is supported by results from other models developed independently.
KeywordsCoagulation Factor VIII Initial concentration Mechanistic model Sensitivity analysis
Mathematics Subject Classification49Q12 92C40 93B35
We thank the Department of Science and Technology (DST) for financial support through Grant Number INT/RUS/RFBR/P-180.
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