Thrombus histopathology in distal versus proximal vessel occlusion: insights and future directions for stroke reperfusion.

Acute ischemic stroke is a leading cause of disability and death worldwide. This commentary highlights the role of thrombus composition in influencing treatment outcomes and therapeutic strategies. Rapid reperfusion through intravenous thrombolysis and mechanical thrombectomy is critical to salvage brain tissue. Distal medium vessel occlusions, accounting for approximately 30% of strokes, often result in persistent disability despite optimal therapy, emphasizing the need to understand factors affecting reperfusion success. Stroke thrombi exhibit marked heterogeneity, comprising red blood cells, fibrin, platelets, neutrophils, and von Willebrand factor. Distal occlusions tend to contain more platelet- and fibrin-rich thrombi and fewer red blood cells compared with proximal occlusions. Platelet- and fibrin-dense thrombi are more resistant to thrombolysis and are associated with longer, more complex thrombectomy procedures, while red blood cell-rich thrombi respond better. Anticoagulation may influence thrombus composition, and novel strategies, including fibrin-specific thrombolytics and combination approaches targeting multiple thrombus components, hold promise for improving reperfusion and functional outcomes.