Title: Association of Anisocytosis with Platelet-Rich Thrombi and Stroke Recurrence in Patients Undergoing Thrombectomy

BACKGROUND: Anisocytosis, indicated by an elevated red blood cell distribution width (RDW), has been associated with poor cardiovascular outcomes. However, its relevance to thrombus composition and long-term outcomes in stroke patients undergoing thrombectomy remains unclear. We investigated whether anisocytosis is associated with histologic thrombus characteristics and long-term prognosis in this population. METHODS: This retrospective multicenter cohort study included 401 patients with acute ischemic stroke who underwent intra-arterial thrombectomy between September 2014 and December 2020. Thrombus composition was assessed using immunohistochemistry to quantify the proportions of fibrin, red blood cells, platelets, and thrombin. Patients were followed for major adverse cardiovascular events, including all-cause mortality, ischemic heart disease, and recurrent ischemic stroke. RESULTS: Among the 401 patients (mean age, 73.1 years; 50.1% male), anisocytosis (RDW>15.7%) was present in 67 (16.7%). Thrombi from patients with anisocytosis had higher platelet content (12.2% vs. 9.1%; P = 0.008) and lower erythrocyte content (30.0% vs. 37.3%; P = 0.007) than those without anisocytosis. During a median follow-up of 38.5 months, anisocytosis was independently associated with increased risk of recurrent ischemic stroke (hazard ratio, 2.61; 95% confidence interval, 1.12-6.10; P = 0.027), but not with overall major adverse cardiovascular events, mortality, or ischemic heart disease. CONCLUSION: Anisocytosis was associated with platelet-rich thrombi and an increased risk of stroke recurrence after thrombectomy. These findings suggest a possible role of red blood cells in platelet-mediated thrombosis and indicate that RDW may have potential prognostic value for identifying patients at higher risk for recurrent events.