Diabetes-Associated Fibrin Enrichment in Cerebral Thrombi and Its Procedural Implications for Mechanical Thrombectomy

Background/Objectives: Diabetes is associated with altered fibrin biology, but its relationship with fibrin content in cerebral thrombi and the procedural relevance of this relationship during mechanical thrombectomy remain unclear. We investigated the association between diabetes and fibrin content in thrombectomy-retrieved cerebral thrombi and whether diabetes-associated differences in fibrin content mediated procedural outcomes of mechanical thrombectomy. Methods: We retrospectively analyzed patients with acute ischemic stroke who underwent mechanical thrombectomy and had retrieved thrombi available for histological analysis. Red blood cell, platelet, and fibrin contents were quantified immunohistochemically. The association between diabetes and fibrin content was evaluated using multivariable linear regression, with complementary sensitivity analyses based on intravenous tissue-type plasminogen activator administration and atrial fibrillation status. Mediation analyses were performed to estimate the indirect effects of diabetes on procedural outcomes through diabetes-associated changes in fibrin content. Results: Among 312 patients, 98 (31.4%) had diabetes. Patients with diabetes had greater fibrin content than those without diabetes (median, 37.0% [interquartile range, 26.4-52.9] vs. 30.9% [17.7-45.0]; p = 0.004), whereas red blood cell and platelet contents did not differ significantly between the groups. Diabetes remained associated with greater fibrin content in the primary adjusted analysis (β = +6.68 percentage points; 95% confidence interval [CI], 2.19-11.18; p = 0.004), and the association persisted after additional conditioning on initial glucose and in sensitivity analyses. Among patients with diabetes, neither HbA1c nor initial glucose was associated with fibrin content. Mediation analyses did not identify a detectable indirect effect of diabetes through fibrin content on successful reperfusion, complete reperfusion, first-pass effect, number of passes, or the requirement for ≥3 passes. Conclusions: Diabetes was independently associated with greater fibrin content in cerebral thrombi retrieved during mechanical thrombectomy, supporting the presence of a diabetes-associated fibrin-enriched thrombus phenotype. However, no detectable indirect effect of diabetes-associated differences in fibrin content on the examined procedural outcomes of mechanical thrombectomy was identified. These findings suggest that although diabetes is associated with a distinct quantitative change in cerebral thrombus composition, a corresponding procedural consequence was not detectable in the present study.