Pathology and Mechanisms Underlying Thrombus Formation in Stroke

The mechanisms underlying atherothrombus and cardiac thrombus formation are complex and multifactorial. Ischemic stroke is characterized by large thrombus formation and vascular occlusion. The degree of plaque disruption and plaque thrombogenicity determine the size of the atherothrombus. Tissue factor-driven thrombin generation contributes to fibrin formation and platelet aggregation. As opposed to collagen, the von Willebrand factor (VWF) and fibrin may provide the scaffolds required for initial platelet adhesion on ruptured plaques. VWF also contributes to occlusive thrombus formation, following plaque disruption. Acute changes in shear stress and oscillatory shear stress can induce superficial erosive injury of plaques and thrombus formation. Atrial fibrillation causes atrial intimal thickening and thrombogenic factor expression, promotes stasis of blood in the left atrium and the left atrial appendage, and can contribute to thrombogenesis and elevated plasma VWF and fibrinogen levels. Coagulation Factor XI is a target for next-generation anticoagulants because it plays an important role in thrombus growth but not in hemostasis.