Thrombin

Abstract Thrombin (factor IIa) is a serine protease that converts fibrinogen into fibrin in blood coagulation. The precursor of thrombin, prothrombin (inactive zymogen), is one of the several coagulation proteins containing γ‐carboxyglutamic acid. Prothrombin is synthesised in the liver and secreted into blood circulation, and is activated by vascular injury by limited proteolysis following upstream activation of the coagulation cascade. Thrombin activity is regulated by serum inhibitors and by its own action. With its procoagulant and anticoagulant functions, it plays a central role in thrombosis and haemostasis. It is an agonist for a number of cellular responses during inflammation and wound repair. Many diseases including stroke and myocardial infarction involve thrombosis; therefore, thrombin is a preferred target of antithrombotic drugs. Drugs available to block thrombin action include heparins, hirudins (lepirudin and bivalirudin), vitamin K antagonists and a new generation of direct thrombin inhibitors such as dabigatran and argatroban. Key Concepts: Thrombin is a serine protease that converts fibrinogen into fibrin and plays a crucial role in haemostasis and thrombosis. During coagulation, factor Xa/Va complex formed on phospholipid or platelet membrane converts prothrombin to thrombin in the presence of Ca 2+ . Thrombin also activates platelets and factors V, VIII and XI to enhance haemostasis. In addition to haemostasis, thrombin plays a major role in inflammation and wound healing, and it is a potent mitogenic factor. Thrombin has anticoagulant effects by activating the protein C pathway and by releasing plasminogen activators from endothelial cells, which promote fibrinolytic cascade. Consequences of thrombosis include vascular diseases such as stroke, myocardial infarction and deep‐vein thrombosis and pulmonary embolism. Both direct and indirect inhibitors are used clinically to treat thrombotic disorders.