Thrombin activatable fibrinolysis inhibitor (TAFI)--how does thrombin regulate fibrinolysis?

Abstract

The thrombin-catalysed conversion of plasma fibrinogen into fibrin and the development of an insoluble fibrin clot are the final steps of the coagulation cascade during haemostasis. A delicate balance between coagulation and fibrinolysis determines the stability of the fibrin clot. Thrombin plays a central role in this process, it not only forms the clot but it is also involved in stabilizing the clot by activating thrombin activatable fibrinolysis inhibitor (TAFI). Activated TAFI protects the fibrin clot against lysis. Here we will discuss the mechanisms for regulation of fibrinolysis by thrombin. The role of the coagulation system for the generation of thrombin and for the activation of TAFI implies that defects in thrombin generation will directly affect the protection of clots against lysis. Thus, defects in activation of TAFI might contribute to the severity of bleeding disorders. Vice versa an increased activation of TAFI due to an increased rate of thrombin generation might lead to thrombotic disorders. Specific inhibitors of activated TAFI or inhibitors that interfere with the generation of thrombin might provide novel therapeutic strategies for thrombolytic therapy. Besides having a role in the regulation of fibrinolysis, TAFI may also have an important function in the regulation of inflammation, wound healing and blood pressure.