Mathematical modeling to investigate dual pathway inhibition by anticoagulant and antiplatelet drugs

Abstract

The purpose of blood coagulation is to halt blood flow from a damaged vessel for the vessel to heal and repair. Blood coagulation occurs as overlapping enzymatic events, which are strongly regulated by platelet surfaces. Coagulation begins when the wall of the blood vessel is injured and ends when aggregated platelets seal the injury. Dual pathway inhibition, in which both antiplatelet and anticoagulant drugs are used in combination, promises therapies for reducing risks of harmful clot development that may lead to coronary and cerebrovascular ischemia. Although information exists concerning the effectiveness and success of dual pathway inhibition therapies, the mechanism remains ambiguous due to a lack of ability to observe detailed biochemical interactions during the dynamic clotting process. Mathematical modeling allows for efficient simulations of the clotting process and provides access to the dynamic concentrations of all proteins, cells, and interactions within the system under the influence of flow. This project builds on a mechanistic mathematical model of flow-mediated coagulation and platelet deposition. A combination of the antiplatelet aspirin and the anticoagulant rivaroxaban is considered in the model, and the clotting process is simulated for various concentrations of drugs and injury types.