Schematic representation of the mechanisms of platelet adhesion and aggregation in flowing blood. In a cylindrical vessel, the velocity profile of particles contained in circulating blood is parabolic; the shear rate decreases from the wall to the center of the lumen inversely to the flow velocity. In a flow field with high shear rate, only GP Ibα interaction with immobilized vWF multimers can initiate the tethering of circulating platelets to the vessel wall and to already adherent platelets. This GP Ibα–dependent interaction supports initially transient bonds, depicted by the ongoing detachment of the 2 top platelets from vWF multimers bound to already activated platelets. The process is amplified by the activation of α_IIbβ₃, which may occur during the transient tethering or through the action of other receptors that bind collagen or other components of exposed vascular or extravascular surfaces (see also Figure 1). The final result is stable attachment of recruited platelets and irreversible membrane binding of soluble adhesive ligand (fibrinogen and vWF), thus providing the substrate for additional recruitment of nonactivated platelets and leading to thrombus growth. Note that nonactivated α_IIbβ₃ cannot bind soluble ligands. The bridging effect of fibrinogen, which is required to stabilize platelet aggregation and resist the effects of high shear stress, only occurs after initial tethering of platelets through the interaction of vWF and GP Ibα. At shear rates less than 500–1,000 s^–1, the adhesive functions of vWF are no longer indispensable, either for initial attachment to a thrombogenic surface or for aggregation. Thus, even in the absence of vWF, collagen receptors (among others) can permit stable adhesive interactions to form rapidly, and fibrin or fibrinogen can bind to platelets to permit aggregation.