Correlation of von Willebrand factor and platelets with acute ischemic stroke etiology and revascularization outcome: an immunohistochemical study

Abstract

BackgroundPlatelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology and the impact these components may have on the clinical/procedural parameters.MethodsCD42b/vWF immunostaining was performed on 288 emboli collected as part of the multicenter STRIP Registry. CD42b/VWF expression and distribution were evaluated. Student’s t-test and χ2 test were performed as appropriate.ResultsThe mean CD42b and VWF content in clots was 44.3% and 21.9%, respectively. There was a positive correlation between platelets and vWF (r=0.64, p<0.001**). We found a significantly higher vWF level in the other determined etiology (p=0.016*) and cryptogenic (p=0.049*) groups compared with cardioembolic etiology. No significant difference in CD42b content was found across the etiology subtypes. CD42b/vWF patterns were significantly associated with stroke etiology (p=0.006*). The peripheral pattern was predominant in atherosclerotic clots (36.4%) while the clustering (patchy) pattern was significantly associated with cardioembolic and cryptogenic origin (66.7% and 49.8%, respectively). The clots corresponding to other determined etiology showed mainly a diffuse pattern (28.1%). Two types of platelets were distinguished within the CD42b-positive clusters in all emboli: vWF-positive platelets were observed at the center, surrounded by vWF-negative platelets. Thrombolysis correlated with a high platelet content (p=0.03*). vWF-poor and peripheral CD42b/vWF pattern correlated with first pass effect (p=0.03* and p=0.04*, respectively).ConclusionsThe vWF level and CD42b/vWF distribution pattern in emboli were correlated with AIS etiology and revascularization outcome. Platelet content was associated with response to thrombolysis.

Distinct platelet F-actin patterns and traction forces on von Willebrand factor versus fibrinogen

“…It is possible that toward cessation of bleeding, it is advantageous for the earliest bound platelets to be hypercontractile and that F-actin fibers formed through the center of the platelet enable maximal forces. Additionally, these F-actin structural and functional differences could be important in clots of different protein content and protein organization, such as the fibrin(ogen)-rich outer shell observed in acute ischemic stroke thrombi (43) and the distribution of VWF within a thrombi that is associated with stroke etiology and revascularization outcome (44).…”

Shell Versus Core Architecture and Biology of Thrombi in Acute Ischemic Stroke: A Systematic Review

“…The development and integration of endovascular treatment for acute ischemic stroke (AIS) have provided the opportunity to study clots retrieved via mechanical thrombectomy (MT), allowing previously unanswered questions about clot composition and stroke etiology to be explored. [1][2][3][4][5][6] Moreover, there has been a growing interest in understanding the factors responsible for the effectiveness of pharmacological and endovascular treatment. 7,8 In general, thrombi have different compositions based on the thrombotic disorder: arterial thrombi obtained from patients with myocardial infarction contain mainly fibrin and other components such as platelets, red blood cells (RBCs), leukocytes, and cholesterol crystals while venous thrombi are composed of RBCs and fibrin with sparse platelets and leukocytes.…”

“…The development and integration of endovascular treatment for acute ischemic stroke (AIS) have provided the opportunity to study clots retrieved via mechanical thrombectomy (MT), allowing previously unanswered questions about clot composition and stroke etiology to be explored. 1–6 Moreover, there has been a growing interest in understanding the factors responsible for the effectiveness of pharmacological and endovascular treatment. 7,8…”