Research Day

History of Anticoagulants

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INTRODUCTION: Arterial and venous thromboembolisms are major causes of morbidity and mortality across the world. They are the leading cause of death and disability in high-income countries and are increasing in middle- and low-income countries. Pharmacological approaches have become pivotal in both prevention and treatment of thromboembolisms. As our understanding of hypercoagulability increased throughout the 20th century, anticoagulants have become a frontline therapy in preventing and reducing adverse outcomes for thromboembolic patients. The progressive discovery of these anticoagulants and their contribution to our evolving understanding of coagulation illustrate the importance of basic science and translational research. RATIONALE: This review provides a historical perspective of anticoagulants with a focus on their initial discovery, mechanism of action, and clinical uses in a way that allows one to appreciate the evolution of pharmacological intervention on coagulation. MATERIALS & METHODS/REVIEW OF LITERATURE: Using PubMed, we searched for primary sources and review articles for the following compounds, their development and discovery: heparin, rivaroxaban, dabigatran, warfarin, hirudin and bivalirudin, streptokinase and urokinase, and platelet inhibitors. In total, 144 sources were used. RESULTS: The first anticoagulant, heparin, was discovered in 1916 by Jay McLean.. In the late 1940s and into the 1950s, a compound that inhibited the synthesis of vitamin K-dependent clotting factors X, IX, VII, and II was developed and named Warfarin. In the 1950s, hirudin, an anticoagulant compound produced by leeches, was isolated and used to develop bivalirudin, a potent thrombin inhibitor. Fast forwarding several decades, research in the 1980s identified specific compounds in the coagulation cascade, including Factor Xa, the activated form of Factor X. Since the discovery of Factor Xa, several new anticoagulants targeting it have been developed, including dabigatran, rivaroxaban, and the newest compound, apixaban. CONCLUSION: The century-long development of anticoagulants has made an incredible impact on medicine. The elucidation of the mechanisms of coagulation since the initial discovery of heparin demonstrates how one scientific discovery can catalyze others, which not only included generations of anticoagulants, but parallel advancements in antiplatelet and fibrinolytic therapies.

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