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.

中文翻译：

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凝血因子 VIII 初始浓度在体外凝血机制模型中的重要性

这项计算研究为凝血蛋白生成了一个假设，其初始浓度极大地影响了凝血过程。许多血液凝固的临床恶性肿瘤是由于凝血因子的初始浓度异常引起的。凝血机制模型的敏感性分析是评估此类异常影响的便捷方法。因此，该研究对最近开发的凝血机制模型进行了关于初始浓度的敏感性分析。正在分析模型敏感性的模型和参数都提供了对血液凝固的新见解：该模型结合了血浆相和血小板膜结合物质的不同方程，并且对初始浓度的敏感性是敏感性分析的一个新维度。