Abstract

The process of blood coagulation is not a simple transformation of fibrinogen to fibrin by the action of thrombin. Rather, this remarkably complex process is a result of numerous transformations mediated by enzymes, activators, inhibitors, platelets, endothelial cells, and leukocytes. Newer studies have also shown that some hemostatic responses are regulated through autonomic control mechanisms. Congenital abnormalities, acquired risk factors, medical procedures, and surgical interventions produce stimuli for hemostatic activation. These conditions necessitate the use of anticoagulant and antithrombotic agents to maintain blood fluidity. Heparin, an anticoagulant that possesses a complex mode of action, has been the only drug available to control thrombosis for many years. Low molecular weight heparin represents a refined and more optimized heparin where the pharmacokinetics and safety have been improved. Vitamin K antagonists are the only drugs available for long-term anticoagulation. Understanding of the hemostatic activation processes, as well as appreciation for the importance of hemostasis in health, has occurred only recently and discoveries still continue. This has led to the development of newer pharmacologic approaches to inhibit and control thrombosis. Synthetic heparin-derived drugs (fondaparinux), thrombin inhibitors, and antiplatelet drugs, have recently become available. The near future should bring factor Xa inhibitors, other coagulation protease inhibitors, additional antiplatelet drugs, non-heparin drugs, and oral formulations. Because of the high morbidity–mortality associated with cardiovascular disease (thrombosis), it will be important to continue the development toward optimized antithrombotic drugs targeted to specific mechanisms with improved pharmacologic properties.