Model of platelet–vessel wall interaction. (A) The initial contact (tethering) of platelets to the extracellular matrix (ECM) is mediated predominantly by GPIbα-VWF interactions. The GPIbα-VWF interaction is essential at high shear rates (> 500 s−1). GPIbα may also interact with P-selectin exposed on activated endothelial cells and thereby contribute to platelet recruitment to the intact vessel wall. (B) At sites of vascular injury, GPVI-collagen interactions initiate cellular activation followed by shifting of integrins to high-affinity state and the release of secondarily acting agonists, most importantly ADP, ATP, and TxA2. GPIb-mediated signaling may amplify GPVI-induced activation pathways. In parallel, exposed tissue factor (TF) locally triggers the formation of thrombin (extrinsic pathway), which in addition to GPVI mediates cellular activation. On the growing thrombus, activation of FXII and FXI also leads to thrombin formation. (C) Activated GPIIb/IIIa (integrin αIIbβ3) together with β1 integrins (not shown) mediates firm adhesion by binding to VWF, fibronectin, and other ligands. Released ADP, ATP, and TxA2 amplify integrin activation on adherent platelets and mediate thrombus growth by activating additional platelets and fibrinogen binding to GPIIb/IIIa. (D) Adherent platelets may recruit leukocytes to the thrombus through GPIbα-MAC1 interactions. This scheme does not exclude the involvement of other receptor-ligand interactions.
