Communications in Information and Systems

Volume 19 (2019)

Number 3

Review of quantitative systems pharmacological modeling in thrombosis

Pages: 219 – 240

DOI: https://dx.doi.org/10.4310/CIS.2019.v19.n3.a1

Authors

Limei Cheng (Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, U.S.A.)

Guo-Wei Wei (Department of Mathematics, Michigan State University, East Lansing, Mi., U.S.A.)

Tarek Leil (Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, U.S.A.)

Abstract

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.

Received 1 September 2019

Published 6 December 2019