Is Clot Composition Associated With Cause of Stroke? A Systematic Review and Meta‐Analysis

Background Prior studies have suggested an association between clot histological composition and cause of stroke. However, the results have been conflicting. Our objective is to provide an updated systematic review and meta‐analysis of the association between clot histological composition and cause of stroke for patients who underwent mechanical thrombectomy. Methods We searched Cochrane Library, Embase, and MEDLINE databases for English language articles reporting clot histology in adult patients who underwent mechanical thrombectomy for acute ischemic stroke between January 2000 and March 2024. Studies included reported on the association between causes of clots and the quantity of red blood cells and fibrin and/or platelets. Random effects meta‐analysis was used. Results A total of 448 records were identified. Of these, 25 studies were included in the qualitative synthesis, and 17 contained data in a format suitable for quantitative review. A total of 1656 patients had continuous data on clot composition and its association with cause of stroke. The pooled mean percentage difference between the cardioembolic group and the large artery atherosclerosis /noncardioembolic group was −10.3% (95% CI −16.3% to −4.4%) for red blood cells and +9.9% (95% CI +4.5% to +15.4%) for fibrin and/or platelets. Only 7 studies reported on overall white blood cells quantity. Of these, the pooled percentage difference of white blood cells between the cardioembolic group and the large artery atherosclerosis/non‐cardioembolic group was +1.1% (95% CI +0.3% to +1.9%). Conclusion Our results suggest that cardioembolic clots have higher fibrin and/or platelets and lower red blood cells compared with large artery atherosclerosis/noncardioembolic clots. However, these differences are unlikely to be of clinical utility in differentiating cause of stroke. Future studies would benefit from more rigorous analysis of clot constituents beyond cellular composition.