Cheng Limei, Wei Guo-Wei, Leil Tarek
Clinical Pharmacology and Pharmacometrics Bristol-Myers Squibb, Princeton, NJ 08540, USA.
Department of Mathematics Michigan State University East Lansing, MI 48824 USA.
Commun Inf Syst. 2019;19(3):219-240. doi: 10.4310/cis.2019.v19.n3.a1. Epub 2019 Dec 6.
Hemostasis and thrombosis are often thought as two sides of the same clotting mechanism whereas hemostasis is a natural protective mechanism to prevent bleeding and thrombosis is a blood clot abnormally formulated inside a blood vessel, blocking the normal blood flow. The evidence to date suggests that at least arterial thrombosis results from the same critical pathways of hemostasis. Analysis of these complex processes and pathways using quantitative systems pharmacological model-based approach can facilitate the delineation of the causal pathways that lead to the emergence of thrombosis. In this paper, we provide an overview of the main molecular and physiological mechanisms associated with hemostasis and thrombosis, and review the models and quantitative system pharmacological modeling approaches that are relevant in characterizing the interplay among the multiple factors and pathways of thrombosis. An emphasis is given to computational models for drug development. Future trends are discussed.
止血和血栓形成通常被认为是同一凝血机制的两个方面，然而止血是一种防止出血的自然保护机制，而血栓形成是血管内异常形成的血凝块，阻碍正常血流。迄今为止的证据表明，至少动脉血栓形成源于相同的关键止血途径。使用基于定量系统药理学模型的方法分析这些复杂的过程和途径，有助于描绘导致血栓形成的因果途径。在本文中，我们概述了与止血和血栓形成相关的主要分子和生理机制，并回顾了在表征血栓形成的多种因素和途径之间相互作用方面相关的模型和定量系统药理学建模方法。重点介绍了用于药物开发的计算模型。还讨论了未来的趋势。
