The coagulation cascade is now recognized to be a series of proteolytic events mainly localized to the surface of activated platelets. Once platelets become activated by exposure to activated endothelium, they release mediators such as P-selectin and von Willebrand factor that promote microvesicle formation and platelet adherence. The microvesicles fuse with the activated platelet membrane, providing tissue factor and its ligand, factor VIIa. Clotting factors bind to adjacent receptors on the membrane, enabling the cascading proteolytic cleavages of zymogens to active enzymes, culminating in thrombin generation. Fibrin formation thus occurs in the sheltered environment of the platelet membrane, where it is localized to the site of injury and protected from circulating inhibitors.