When the fibrous cap is breached or eroded, subendothelial collagen, von Willebrand factor, and lipid core material become exposed to flowing blood. Platelets bind via glycoprotein receptors to collagen and von Willebrand factor, become activated, change shape, and release ADP and thromboxane A2, which recruit more platelets. Activated platelets express glycoprotein IIb/IIIa, which binds fibrinogen and links platelets into aggregates. This platelet plug is the first layer of the thrombus.
In parallel, exposed tissue factor from the plaque and from injured cells initiates the coagulation cascade. Factor VIIa bound to tissue factor activates factor X, which with factor Va converts prothrombin to thrombin. Thrombin cleaves fibrinogen into fibrin monomers that polymerize into a mesh, and it also activates factor XIII to cross-link the mesh and further activates platelets. The result is a platelet-fibrin thrombus, often called a white thrombus in its platelet-rich head and a red thrombus where fibrin and trapped red cells dominate. Growth of this mass narrows the lumen progressively; a fully occlusive thrombus stops antegrade flow, while a mural or partially occlusive thrombus leaves a residual channel.