Experimental models of thrombosis. Platelets, red blood cells, monocytes, and granulocytes circulate in blood whereas endothelial cells line the vessel wall. Plasma proteins, including vWF, fibrinogen and other coagulation proteins, and microparticles are also present in the circulation. (A) Upon laser-induced injury of the vessel wall, vWF mediates the interaction of platelets with the endothelium. Tissue factor in the vessel wall leads to thrombin generation. Thrombin activates mouse platelets via the PAR4 receptor (inset). Activated platelets undergo calcium mobilization and the release of ADP and thromboxane A₂ (TxA₂) to accelerate platelet recruitment and activation and the formation of a platelet thrombus. These platelets express P-selectin, and leukocyte microparticles expressing PSGL-1 and tissue factor accumulate in the thrombus through the interaction of P-selectin with PSGL-1 (inset). The concentration of tissue factor initiates coagulation, the generation of more thrombin, and the propagation of a fibrin clot. (B) Upon vessel wall oxidative injury with ferric chloride, the endothelium is denuded and the subendothelial matrix exposed. Platelets interact with the matrix via GPIb-V-IX and α_IIbβ₃ on the platelet membrane and collagen and vWF in the matrix. Glycoprotein VI (GPVI) binding to collagen is required for platelet activation, and activated platelets undergo calcium mobilization and the release of ADP and thromboxane A₂ (inset) to accelerate platelet recruitment and activation and the formation of a thrombus. These platelets express P-selectin, and microparticles expressing PSGL-1 and tissue factor accumulate in the thrombus through the interaction of P-selectin with PSGL-1 (inset). The concentration of tissue factor leads to coagulation, the generation of more thrombin, and the propagation of a fibrin clot.