ABSTRACT
Most of the currently available anticoagulants used for the prevention and treatment of venous and arterial thromboembolism require antithrombin for their anticoagulant effect and (with the exception of fondaparinux) produce their anticoagulant effect by inhibiting multiple coagulation factors. Heparin, LMWH, and warfarin all produce at least a component of their anticoagulant effect by inhibiting thrombin. The conversion of the zymogen precursor prothrombin to thrombin is the final common pathway of blood coagulation. Thrombin is a versatile enzyme. It not only converts fibrinogen to fibrin, but also activates FXIII, rendering fibrin resistant to fibrinolysis. With the assistance of thrombomodulin, thrombin cleaves protein C and thrombin-activatable fibrinolysis inhibitor (TAFI) as well. Thrombin upregulates its own production by activating FVIII and FV, cofactors for tenase and prothrombinase, as well as FXI and FVII. It also acts as a platelet agonist. In this way, thrombin is able to provide positive feedback and amplify hemostasis. Thrombin’s ubiquitous role in maintaining hemostasis makes it a prime target for newer, more specific anticoagulant drugs.
