Histopathologic Composition of Cerebral Thrombi of Acute Stroke Patients Is Correlated with Stroke Subtype and Thrombus Attenuation

Abstract

IntroductionWe related composition of cerebral thrombi to stroke subtype and attenuation on non-contrast CT (NCCT) to gain more insight in etiopathogenesis and to validate thrombus attenuation as a new imaging biomarker for acute stroke.MethodsWe histopathologically investigated 22 thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fresh, lytic or organized. Second, percentages of red blood cells (RBCs), platelets and fibrin and number of red, white (respectively RBCs or platelets outnumbering other components with ≥15%) or mixed thrombi were compared between large artery atherosclerosis (LAA), cardioembolism, dissection and unknown subtype. Third, correlation between attenuation and RBCs, platelets and fibrin was calculated using Pearson's correlation coefficients (r).ResultsThrombi were fresh in 73% (n = 16), lytic in 18% (n = 4) and organized in 9% (n = 2). The stroke cause was LAA in eight (36%), cardioembolism in six (27%), dissection in three (14%), and unknown in five (23%) patients. LAA thrombi showed the highest percentage RBCs (median 50 (range 35–90)), followed by dissection (35 (20–40), p = 0.05), cardioembolism (35 (5–45), p = 0.013) and unknown subtype (25 (2–40), p = 0.006). No differences in platelets (p = 0.16) and fibrin (p = 0.52) between subtypes were found. LAA thrombi were classified as red or mixed (both n = 4), cardioembolisms as mixed (n = 5) or white (n = 1) and dissection as mixed (n = 3). There was a moderate positive correlation between attenuation and RBCs (r = 0.401, p = 0.049), and weak negative correlations with platelets (r = −0.368, p = 0.09) and fibrin (r = −0.073, p = 0.75).ConclusionsThe majority of cerebral thrombi is fresh. There are no differences in age of thrombi between subtypes. LAA thrombi have highest percentages RBCs, cardioembolism and unknown subtype lowest. No relationship exists between subtype and platelets or fibrin percentages. We found a correlation between the RBC-component and thrombus attenuation, which improves validation of thrombus attenuation on NCCT as an imaging biomarker for stroke management.

Negative Susceptibility Vessel Sign and Underlying Intracranial Atherosclerotic Stenosis in Acute Middle Cerebral Artery Occlusion

“…13 Recently, several investigators reported the results of histologic studies analyzing the composition of the clots retrieved by mechanical thrombectomy in patients with acute ischemic stroke. 6,[14][15][16] These studies demonstrated that the presence of an SVS on GRE imaging was notably associated with a higher red blood cell content in the clots, whereas an absence of SVS was associated with fibrin-rich clots. Fibrin-dominant clots are usually formed because of injury to the endothelium overlying the complicated atheromatous plaque.…”

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

“…Our study also advances the understanding of the pathophysiology of the SVS on GRE imaging. The few previous studies performing histopathologic analysis on human intracranial clots retrieved by mechanical thrombectomy in acute stroke have looked only at analysis of blood cell composition using hematoxylin and eosin2, 3, 4 or immunohistochemical staining 5, 6, 7. This is the first report of molecular analysis including mRNA expression of inflammatory mediators in retrieved clots.…”

“…Mechanical thrombectomy is notable because it allows for histologic evaluation of clots retrieved from human intracranial arteries, potentially broadening our insight into stroke etiology as well as our understanding of clot appearance on imaging studies. Several recent studies involving the histologic analysis of intracranial clots retrieved by mechanical thrombectomy in acute stroke patients have focused on blood cell composition in clots using either hematoxylin and eosin or immunohistochemical staining 2, 3, 4, 5, 6, 7…”

Histologic Analysis of Retrieved Clots in Acute Ischemic Stroke: Correlation with Stroke Etiology and Gradient-Echo MRI

“…Recent studies suggested that histologic examination of retrieved clots can offer new insights into the pathogenesis of acute stroke due to intracranial large-vessel occlusion. [6][7][8][9] However, it is currently unclear whether clot-composition analysis is helpful to predict a stroke mechanism in acute large-vessel occlusion. Only a few studies have been conducted on this topic, and prior studies have yielded only vague and contradictory results.…”

“…Only a few studies have been conducted on this topic, and prior studies have yielded only vague and contradictory results. [8][9][10] In addition, histopathologic analysis of retrieved clots allows understanding of the pathologic basis of early vessel signs on imaging studies in patients with acute ischemic stroke. Several studies have shown that the hyperattenuated vessel sign on CT and the susceptibility vessel sign on gradient-echo (GRE) MR imaging were more often associated with erythrocyte-rich thrombi (red thrombi) than fibrin-rich thrombi (white thrombi).…”