Clot Composition Analysis as a Diagnostic Tool to Gain Insight into Ischemic Stroke Etiology: A Systematic Review

Mechanical thrombectomy renders the occluding clot available for analysis. Insights into thrombus composition could help establish the stroke cause. We aimed to investigate the value of clot composition analysis as a complementary diagnostic tool in determining the etiology of large vessel occlusion (LVO) ischemic strokes (International Prospective Register of Systematic Reviews [PROSPERO] registration # CRD42020199436). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we ran searches on Medline (using the PubMed interface) and Web of Science for studies reporting analyses of thrombi retrieved from LVO stroke patients subjected to mechanical thrombectomy (January 1, 2006 to September 21, 2020). The PubMed search was updated weekly up to February 22, 2021. Reference lists of included studies and relevant reviews were hand-searched. From 1,714 identified studies, 134 eligible studies (97 cohort studies, 31 case reports, and six case series) were included in the qualitative synthesis. Physical, histopathological, biological, and microbiological analyses provided information about the gross appearance, mechanical properties, structure, and composition of the thrombi. There were non-unanimous associations of thrombus size, structure, and composition (mainly proportions of fibrin and blood formed elements) with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) etiology and underlying pathologies, and similarities between cryptogenic thrombi and those of known TOAST etiology. Individual thrombus analysis contributed to the diagnosis, mainly in atypical cases. Although cohort studies report an abundance of quantitative rates of main thrombus components, a definite clot signature for accurate diagnosis of stroke etiology is still lacking. Nevertheless, the qualitative examination of the embolus remains an invaluable tool for diagnosing individual cases, particularly regarding atypical stroke causes.