Pathogenesis of thrombosis: Cellular and pharmacogenetic contributions

Abstract

Our understanding of thrombosis formation has evolved significantly ever since physician Rudolf Virchow proposed his "triad" theory in 1856. Modern science has elucidated the mechanisms of stasis, hypercoagulability, and endothelial dysfunction. Today, we have a firm understanding of the key molecular factors involved in the coagulation cascade and fibrinolytic system, as well as the underlying genetic influences. This knowledge of cellular and genetic contributors has been translated into diverse pharmaceutical interventions. Here, we examine the molecular and cellular mechanisms of thrombosis and its associated pathologies. We also review the current state of pharmacologic interventions, including pro- and anti-thrombotics, direct oral anticoagulants, and anti-platelet therapies. The pharmacogenetic factors that guide clinical decision making and prognosis are described in detail. Finally, we explore new approaches to thrombosis drug discovery, repurposing, and diagnostics. We argue that network biology tools will enable a systems pharmacology revolution in the next generation of interventions, facilitating precision medicine applications and ultimately leading to improved patient outcomes.