Illustrated Review: History of Anticoagulant Pharmacology

Anticoagulants are the drugs of choice for the management of various thromboembolic disorders affecting both arteries and veins. This review delineates the pharmacologic characteristics of currently available anticoagulants. The potential roles of novel investigational anticoagulants are also briefly discussed. Although heparins and warfarin are conventional anticoagulants with a number of limitations, a thorough understanding of their pharmacologic properties can help prevent undesirable outcomes. Due to strong clinical evidence and more favorable pharmacologic characteristics, direct oral anticoagulants are currently utilized in place of heparins and warfarin to treat a range of thromboembolic conditions, including prevention of cardioembolic stroke and systemic embolism secondary to atrial fibrillation and the management of venous thromboembolism. However, novel potent anticoagulants with low bleeding risk are needed. Emerging targets for the development of anticoagulants are clotting factor XI (FXI) and clotting factor XII (FXII). Currently, many FXI inhibitors are undergoing phase II or III clinical studies, whereas FXII inhibitors are mainly in the preclinical stage. Targeting FXI and FXII appears to promote low bleeding propensity. Overall, the fundamental pharmacologic background of anticoagulants promotes better understanding of their current clinical applications. Progress in the development of FXI and FXII inhibitors may lead to innovative, effective anticoagulants with favorable safety profiles.