Stroke etiology, thrombus composition, and patient outcomes: A histopathological and clinical perspective

Growing evidence suggests that thrombus composition may influences embolic stroke severity, treatment response, and patient outcomes. While previous studies have characterized histopathological differences between cardioembolic stroke (CES) and atheroembolic stroke (AES), less is known about embolic strokes of undetermined source (ESUS). This study examines the relationship between embolic stroke etiology, thrombus composition, and clinical outcomes to improve classification and guide therapeutic strategies.

This retrospective study included 323 patients with acute embolic ischemic stroke treated with mechanical thrombectomy. Stroke etiology was classified as CES (n = 151), AES (n = 71), or ESUS (n = 81). Histopathological examination was performed on 127 retrieved thrombi, assessing fibrin architecture, platelet distribution, neutrophil content, and red blood cell integrity. Clinical parameters, including National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), length of hospital stay, and in-hospital mortality, were analyzed. Statistical models examined associations between thrombus characteristics, stroke etiology, and functional recovery.

CES thrombi exhibited higher platelet and neutrophil content, with a dense, centrally concentrated platelet distribution consistent with fibrin-rich, compact thrombi. In contrast, AES thrombi showed a more diffuse, net-like distribution of platelets, aligning with high-shear conditions in stenotic arteries. ESUS thrombi closely resembled AES but contained a heterogeneous fibrin profile, including the highest proportion of compact fibrin, suggesting alternative thrombus maturation mechanisms. Patients with AES exhibited the poorest functional recovery (lowest NIHSS and mRS improvement), despite successful recanalization. ESUS had the highest in-hospital mortality. Stroke mechanism was significantly associated with both thrombus composition and patient outcomes in this study.

Thrombus histopathology varies significantly by stroke etiology, with platelet distribution emerging as a strong classifier. ESUS thrombi exhibit hybrid features, emphasizing the need for improved classification. Clinical outcomes differed across etiologies, with AES patients experiencing the slowest recovery and ESUS patients exhibiting the highest in-hospital mortality. Integrating thrombus characteristics into risk stratification models, secondary prevention strategies, and artificial intelligence-driven classification may enhance acute stroke management.