Platelet aggregation: involvement of thrombin and fibrin(ogen)

Platelets play a key role in hemostasis and thrombosis. The formation of a platelet plug is accompanied by the generation of thrombin, which results in the generation of fibrin required for stabilization of the platelet plug. Platelet plug formation and coagulation are closely linked processes. Thrombin is a potent platelet activator, which proceeds through proteolysis of the protease activated receptors (PARs). Furthermore, thrombin binds glycoprotein Ib(alpha), which amplifies platelet activation by accelerating PAR-1 activation, and possibly also by direct signaling events through glycoprotein Ib(alpha). Moreover, thrombin's specificity towards other substrates changes after binding glycoprotein Ib(alpha). Fibrinogen and fibrin, the end product of the coagulation cascade, are also involved in platelet aggregation. Both fibrinogen and fibrin bind the integrin alpha(IIb)beta(3), and another fibrin receptor involved in platelet aggregation has been postulated. This review will discuss the role of thrombin and fibrin(ogen) in platelet functioning, and will highlight pathways at the crossroad of coagulation and platelet functioning, which are potential targets for antithrombotic therapy.