Thrombine

Thrombin is a central serine protease of the blood coagulation system. It is the active enzyme derived from its zymogen precursor, prothrombin (factor II), a vitamin K–dependent glycoprotein produced by the liver. Prothrombin circulates in the bloodstream until it is activated in response to vascular injury.

Activation and function occur in the common pathway of coagulation. The prothrombinase complex—composed of factor Xa, factor Va, calcium ions, and a phospholipid surface—converts prothrombin to thrombin (IIa). Thrombin then converts fibrinogen into fibrin, initiates fibrin polymerization, and activates factor XIII to crosslink the fibrin network, stabilizing clots. It also amplifies the coagulation cascade by activating factors V, VIII, and XI and stimulates platelets through protease-activated receptors on their surface, promoting further clot formation.

Regulation of thrombin activity is essential to prevent excessive clotting. Thrombin is inhibited by antithrombin III, with heparin markedly accelerating this inhibition. Endothelial cells present thrombomodulin, which binds thrombin and redirects its activity toward activating protein C; activated protein C, with protein S, downregulates factors Va and VIIIa, providing an anticoagulant feedback mechanism.

Clinical relevance includes disorders arising from imbalanced thrombin generation, such as bleeding or thrombosis. Therapeutically, direct thrombin inhibitors (for example, dabigatran) reduce thrombin activity, and vitamin K antagonists decrease synthesis of thrombin by lowering levels of vitamin K–dependent clotting factors. Topical thrombin preparations are used to aid hemostasis during surgery.