Susree M, Anand M
Department of Chemical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Telangana, 502285, India.
Acta Biotheor. 2018 Sep;66(3):201-212. doi: 10.1007/s10441-018-9329-8. Epub 2018 May 14.
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.
这项计算研究针对一种凝血蛋白提出了一个假设，该蛋白的初始浓度对凝血过程有很大影响。许多临床凝血恶性肿瘤是由于凝血因子初始浓度异常所致。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，该研究针对最近开发的凝血机制模型，给出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为凝血提供了更新的见解：该模型纳入了针对血浆相和血小板膜结合物质的不同方程，对初始浓度的敏感性是敏感性分析中的一个新维度。结果表明，模型预测对于因子VIII初始浓度的变化最为不确定，并且这一假设得到了独立开发的其他模型结果的支持。
