Platelet protagonist/antagonist: understanding the distinguishing characteristics of anticoagulants.

Clinical coagulation laboratory tests do not accurately reflect hemostasis and thrombosis in vivo. Thrombin generation in vivo occurs in 3 overlapping phases: initiation, priming, and propagation. During initiation, injury to the vessel wall exposes the cells to tissue factors, which lead to the production of small amounts of thrombin. During priming, the thrombin that is generated initially binds to platelets and activates them through protease-activated receptors. During the propagation phase, factor X is activated by the factor IXa/VIIIa complex that is assembled on the activated platelet surface. Subsequent formation of factor Xa/Va complexes on the platelet surface leads to a burst of thrombin and fibrin formation. Pharmacologic concentrations of a direct thrombin inhibitor, bivalirudin, inhibit thrombin-induced activation of platelets to a greater extent than pharmacologic concentrations of unfractionated heparin.