Red blood cell (RBC) content, fibrin/platelet (F/P) composition, and clot length are critical determinants of mechanical thrombectomy (MT) outcomes in acute ischemic stroke. However, clinical evidence remains fragmented due to methodological heterogeneity. We systematically evaluated the association between these histologic features, structural heterogeneity, and angiographic/procedural outcomes.

Following PRISMA guidelines (PROSPERO: CRD20251110596), we searched PubMed and MEDLINE for studies published between January 2013 and July 2024. Inclusion criteria comprised adult studies analyzing histology-derived clot composition or length in relation to MT outcomes. Primary outcomes were successful reperfusion (TICI ≥2b) and first-pass effect (FPE). Quantitative pooling was performed for non-overlapping datasets with low-to-moderate risk of bias using random-effects models.

Forty-eight studies (∼7000 patients) were included. Qualitative synthesis revealed that RBC-rich clots are consistently associated with higher rates of successful reperfusion, FPE, fewer passes, and shorter procedure times. Quantitatively, cases achieving successful reperfusion had significantly higher mean RBC content (MD: 11.70%; 95% CI: 4.92%–18.48%). Conversely, F/P-rich and longer clots were linked to lower reperfusion rates and increased distal embolization. F/P-rich clots achieving TICI ≥2b had significantly lower mean content than those failing (MD: −9.02%; 95% CI: −16.72% to −1.33%). Additionally, structural heterogeneity was identified as an independent predictor of reduced FPE.

Clot composition, heterogeneity, and length are significantly associated with mechanical thrombectomy outcomes, although causal relationships cannot be established given the predominantly observational nature of the included studies. Translating these biological insights into clinical practice requires standardized histological definitions and the development of real-time intraprocedural characterization to facilitate adaptive, clot-informed treatment strategies.