Association Between Thrombus Composition and Etiology in Patients With Acute Ischemic Stroke Treated by Thrombectomy

BACKGROUND: In ischemic stroke due to large vessel occlusion, cerebral blood flow is impaired by thromboemboli, which can originate from various sources in the body. A better understanding of thromboembolus composition can improve our understanding of the underlying pathophysiology and potentially guide improvement of prevention strategies. The aim of this study therefore was to perform a large-sample multi-parameter quantitative histological analysis of retrieved thromboemboli from stroke patients. METHODS: Thromboemboli (n=501) were collected from thrombectomy-treated ischemic stroke patients at AZ Groeninge Hospital (Kortrijk, Belgium) and CHU Lille (Lille, France). Stroke etiology was determined by the treating stroke specialist using the TOAST classification system (Trial of ORG 10172 in Acute Stroke Treatment). Extensive histological analysis, blinded to stroke etiology, was performed for key thrombus constituents including red blood cells (RBCs), platelets, fibrin, von Willebrand Factor, leukocytes, citrullinated histone H3 (as a marker for neutrophil extracellular traps), and extracellular (ex)DNA. Quantitative histology results were linked to etiology. RESULTS: Compared with large-artery atherosclerotic thromboemboli, cardioembolic thromboemboli contained significantly fewer RBCs and significantly more platelets, fibrin, leukocytes, and exDNA. Interestingly, cryptogenic thromboemboli contained relatively low amounts of RBCs and high amounts of platelets, similar to cardioembolic thromboemboli. A multivariable logistic regression model indicated that it is difficult to predict stroke etiology based on the individual thrombus composition. CONCLUSIONS: Based on a large sample cohort of stroke thromboemboli, we found that cardiac thromboemboli contained fewer RBCs and more platelets than atherosclerotic thromboemboli and that cryptogenic thromboemboli have a similar composition to cardiac thromboemboli in terms of RBCs and platelets.