Approaches in anticoagulation: rationales for target positioning

Abstract

Heparin and warfarin are the most widely used anticoagulants for the prophylaxis and treatment of thrombus-based diseases. These anticoagulants, however, have well-known clinical limitations, such as a slow onset of action and a narrow therapeutic window. An ideal small-molecule non-peptide inhibitor should have an immediate onset of action, oral bioavailability and an improved therapeutic action and side-effect profile, compared to established therapies. In this review, the current concepts and hypotheses of the numerous anticoagulant approaches are analyzed and evaluated, with emphasis on animal models, genetic disorders and compound profiling. Selected factors of the coagulation cascade and modulators of endogenous fibrinolysis are examined to determine if they represent promising drug targets in antithrombotic therapy.