Kinetics of the coagulation cascade including the contact activation system: sensitivity analysis and model reduction
Kinetics of the coagulation cascade including the contact activation system: sensitivity analysis and model reduction
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DOI：
10.1007/s10237-019-01134-4
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发表时间：
2019-08-01
影响因子：
3.5
通讯作者：
Nicoud, Franck
中科院分区：
文献类型：
--
作者：
Rojano, Rodrigo Mendez;Mendez, Simon;Nicoud, Franck
血栓形成是接触式血液医疗器械研制中的主要问题之一。本文重点对血栓形成的一个方面--凝血级联进行建模，凝血级联由设备表面的接触激活启动并形成凝血酶。现有的模型通过一系列反应来表示凝固级联，通常在静止的等离子体中求解。然而，动力学模型中涉及的大参数不确定性会影响该方法的预测能力。此外，动力学模型的大量反应阻碍了它们在医疗设备中遇到的复杂流动结构的模拟中的使用。在当前的工作中，这两个问题都得到了解决，以提高动力学模型的适用性和保真度。通过两种不同的技术进行敏感性分析，以确定现有的凝聚级联详细动力学模型中最敏感的参数。结果被用于选择一种新的仅依赖于8个化学反应器的凝聚级联简化模型的形式。然后，一旦通过贝叶斯推理对其参数进行了校准，该模型对不同的初始条件显示出良好的预测能力。
Thrombus formation is one of the main issues in the development of blood-contacting medical devices. This article focuses on the modeling of one aspect of thrombosis, the coagulation cascade, which is initiated by the contact activation at the device surface and forms thrombin. Models exist representing the coagulation cascade by a series of reactions, usually solved in quiescent plasma. However, large parameter uncertainty involved in the kinetic models can affect the predictive capabilities of this approach. In addition, the large number of reactions of the kinetic models prevents their use in the simulation of complex flow configurations encountered in medical devices. In the current work, both issues are addressed to improve the applicability and fidelity of kinetic models. A sensitivity analysis is performed by two different techniques to identify the most sensitive parameters of an existing detailed kinetic model of the coagulation cascade. The results are used to select the form of a novel reduced model of the coagulation cascade which relies on eight chemical reactors only. Then, once its parameters have been calibrated thanks to the Bayesian inference, this model shows good predictive capabilities for different initial conditions.