Quantitative histopathological analysis of thrombi retrieved by mechanical thrombectomy and their association with stroke aetiology.

Abstract

Background and purpose: Approximately 25% of acute large vessel occlusive (LVO) ischaemic strokes are of unknown thrombotic origin, and there is a need to establish the aetiology to guide subsequent preventative measures. The aim of this study was to quantify thrombus composition in patients with LVO and explore associations between thrombus composition and stroke aetiology.

Methods: Thrombi were extracted from 132 patients with acute ischaemic stroke. Erythrocytes, leucocytes and F+P (fibrin+platelet) proportions were assessed in tissue sections stained with H&E, while CD3⁺ T cells and neutrophil extracellular traps (NETs) were quantified in immunohistochemistry-stained sections. Thrombus components, clinical parameters and interventional variables were compared between different stroke subtypes defined by Trial of ORG 10172 in Acute Stroke Treatment criteria.

Results: F+P composition was significantly higher (p<0.001) and erythrocyte proportions were significantly lower (p<0.001) in cardioembolic thrombi than in large artery atherosclerosis thrombi. The composition of thrombi from undetermined aetiology strokes resembled that from cardioembolic strokes. CD3⁺ T cell and NET proportions were not significantly different between stroke subtypes. CD3⁺ density per unit area was associated with the occlusive site, being significantly higher in the anterior circulation than the posterior circulation (p=0.004). Cardioembolic strokes were more common in the anterior circulation than large artery atherosclerosis strokes (p=0.002). Recanalisation time was significantly longer for large artery atherosclerosis emboli than for cardioembolic emboli (p=0.032).

Conclusion: There is significant heterogeneity in thrombus composition among different stroke subtypes. The quantitative assessment of thrombus composition may be a useful biomarker of stroke aetiology, and strokes of undetermined aetiology may be more likely to have a cardioembolic origin.