Thrombi from stroke due to cardioembolic etiology have higher CD11b-positive cells compared to large artery atherosclerosis

Identifying the underlying etiology of ischemic stroke is crucial for implementing effective stroke prevention measures. In the era of thrombectomy, ischemic stroke thrombus composition has gained considerable interest in the recent years. However, only a limited studies have analyzed the inflammatory milieu of the thrombus in association with stroke etiology. Atrial Fibrillation (AF), a common etiology of large strokes, is difficult to detect, but is known to be an inflammatory disease with a dominance of CD11b cell types (characterizes bone marrow derived myeloid cells such as monocytes, neutrophils, macrophages, and natural killer cells) in the atria. We hypothesized that thrombi from ischemic stroke patients with AF will have increased CD11b cell types as compared to other stroke etiologies. 51 ischemic stroke thrombi were stained for CD11b. The relationship between stroke etiology (TOAST - Trial of ORG 10172 in Acute Stroke Treatment) and number of CD11b positive cells was assessed. Cardioembolic thrombi contained significantly higher number of CD11b positive cells (248.2 ± 137.4, n = 27) as compared to strokes from large artery atherosclerosis (138.3 ± 92.1, n = 11, p = 0.01). Similarly, thrombi from patients with cryptogenic stroke had significantly higher number of CD11b positive cells, when compared to thrombi from patients with strokes from large artery atherosclerosis ((212.1 ± 104.8 vs. 138.3 ± 92.1, p = 0.04). Our study suggests that increased expression of CD11b in ischemic stroke thrombi characterizes strokes from cardioembolic etiology. It elucidates atrial substrate inflammation driven by CD11b positive leukocytes, which leads to thrombogenesis and ischemic stroke. The shared histology of cardioembolic and cryptogenic strokes suggests that many of the cryptogenic strokes may be due to occult AF.