Scheme of dual role of collagen in thrombus formation. Collagen binds and facilitates FXII activation, which results in sequential activation of FXI and FIX, and subsequent coagulation. Collagen-adhered platelets become activated via their GPVI receptors. Platelet signaling via LAT and PLCγ2 results in potent Ca²⁺ rises and surface exposure of PS. This procoagulant surface mediates the formation of coagulation factor complexes that causes generation of FXa and thrombin. The formed thrombin in turn feeds back to increase PS exposure. Jointly, these pathways lead to massive formation of platelet-fibrin clots, even under conditions where tissue factor is limitedly available.