Immunohistochemical Analysis of Cerebral Thrombi Retrieved by Mechanical Thrombectomy from Patients with Acute Ischemic Stroke

Abstract

Mechanical thrombectomy is a novel treatment option for patients with acute ischemic stroke (AIS). Only a few studies have previously suggested strategies to categorize retrieved clots according to their histologic composition. However, these reports did not analyze potential biomarkers that are of importance in stroke-related inflammation. We therefore histopathologically investigated 37 intracerebral thrombi mechanically retrieved from patients with AIS, and focused on the composition of immune cells and platelets. We also conducted correlation analyses of distinctive morphologic patterns (erythrocytic, serpentine, layered, red, white, mixed appearance) with clinical parameters. Most T cells and monocytes were detected in erythrocytic and red clots, in which the distribution of these cells was random. In contrast, von Willebrand factor (vWF)-positive areas co-localized with regions of fibrin and collagen. While clots with huge amounts of vWF seem to be associated with a high National Institute of Health Stroke Scale score at admission, histologic findings could not predict the clinical outcome at discharge. In summary, we provide the first histologic description of mechanically retrieved intracerebral thrombi regarding biomarkers relevant for inflammation in ischemic stroke.

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…”

Dissecting stroke for anti-VWF therapeutics

“…Recent studies indeed suggest that thrombus tissues dissected from patients with ischemic stroke vary structurally and in their VWF content. 2 Second, the authors demonstrate that VWF-rich thrombi aspirated from sites of vascular occlusions are also extensively stained for fibrin.…”

“…This study was inspired by the detection of substantial, but variable, amounts of VWF in thrombus tissues retrieved from patients with ischemic stroke or those with myocardial infarction. [1][2][3] The authors show that in a mouse model, occlusive VWF-rich thrombi in MCA induced by localized injury were rapidly resolved by the infusion of the recombinant human ADAMTS13. The VWF-rich thrombi were resistant to thrombolysis by tissue plasminogen activator (t-PA), which catalyzes the conversion of plasminogen to plasmin to facilitate fibrinolysis.…”

“…As of January 2016, an estimated 686 197 CBUs have been stored, and nearly 40 000 transplants using UCB have been performed worldwide. 2,3 Unfortunately, CBUs do not uniformly engraft. 4 Reports in children and adults suggest that UCB transplantation is typically associated with a marked delay in hematopoietic recovery, with about 10% to 20% of patients never engrafting at all.…”