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

Background Platelets 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. Methods CD42b/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. Results The 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). Conclusions The 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.

[1]  J. B. Salom,et al.  Clot Composition Analysis as a Diagnostic Tool to Gain Insight into Ischemic Stroke Etiology: A Systematic Review , 2021, Journal of stroke.

[2]  A. Demchuk,et al.  Association between clot composition and stroke origin in mechanical thrombectomy patients: analysis of the Stroke Thromboembolism Registry of Imaging and Pathology , 2021, Journal of NeuroInterventional Surgery.

[3]  D. Kallmes,et al.  High-resolution scanning electron microscopy for the analysis of three-dimensional ultrastructure of clots in acute ischemic stroke , 2020, Journal of NeuroInterventional Surgery.

[4]  D. Kallmes,et al.  Per-pass analysis of acute ischemic stroke clots: impact of stroke etiology on extracted clot area and histological composition , 2020, Journal of NeuroInterventional Surgery.

[5]  M. Ollenschleger,et al.  Clot composition of embolic strokes of undetermined source: a feasibility study , 2020, BMC Neurology.

[6]  Xiuli Zeng,et al.  Differences in Pathological Composition Among Large Artery Occlusion Cerebral Thrombi, Valvular Heart Disease Atrial Thrombi and Carotid Endarterectomy Plaques , 2020, Frontiers in Neurology.

[7]  M. Forsting,et al.  Is Histologic Thrombus Composition in Acute Stroke Linked to Stroke Etiology or to Interventional Parameters? , 2020, American Journal of Neuroradiology.

[8]  Si Eun Kim,et al.  Development of a predictive scale for cardioembolic stroke using extracted thrombi and angiographic findings , 2020, Journal of Clinical Neuroscience.

[9]  Dennis H. Murphree,et al.  Orbit image analysis machine learning software can be used for the histological quantification of acute ischemic stroke blood clots , 2019, PloS one.

[10]  D. Kallmes,et al.  Platelet-rich emboli are associated with von Willebrand factor levels and have poorer revascularization outcomes , 2019, Journal of NeuroInterventional Surgery.

[11]  J. Olivot,et al.  Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis , 2019, Neurology.

[12]  Manuel Stritt,et al.  Orbit Image Analysis: An open-source whole slide image analysis tool , 2019, bioRxiv.

[13]  M. Bacigaluppi,et al.  Insights from thrombi retrieved in stroke due to large vessel occlusion , 2019, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  L. Desender,et al.  Structural analysis of ischemic stroke thrombi: histological indications for therapy resistance , 2019, Haematologica.

[15]  J. Weisel,et al.  The Role of von Willebrand Factor, ADAMTS13, and Cerebral Artery Thrombus Composition in Patient Outcome Following Mechanical Thrombectomy for Acute Ischemic Stroke , 2018, Medical science monitor : international medical journal of experimental and clinical research.

[16]  W. Heindel,et al.  Ischemic Stroke: What Does the Histological Composition Tell Us About the Origin of the Thrombus? , 2017, Stroke.

[17]  M. Krizmaric,et al.  Clinical role of von Willebrand factor in acute ischemic stroke , 2017, Wiener klinische Wochenschrift.

[18]  C. Zimmer,et al.  Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke , 2016, Stroke.

[19]  C. Zimmer,et al.  The Impact of Histological Clot Composition in Embolic Stroke , 2016, Clinical Neuroradiology.

[20]  L. Desender,et al.  ADAMTS13-mediated thrombolysis of t-PA-resistant occlusions in ischemic stroke in mice. , 2016, Blood.

[21]  W. Hacke,et al.  Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome: a systematic review , 2016, Journal of NeuroInterventional Surgery.

[22]  V. Costes,et al.  High CD3+ Cells in Intracranial Thrombi Represent a Biomarker of Atherothrombotic Stroke , 2016, PloS one.

[23]  J. Heo,et al.  Histologic features of acute thrombi retrieved from stroke patients during mechanical reperfusion therapy , 2016, International journal of stroke : official journal of the International Stroke Society.

[24]  S. D. De Meyer,et al.  The VWF-GPIb axis in ischaemic stroke: lessons from animal models , 2016, Thrombosis and Haemostasis.

[25]  C. Kleinschnitz,et al.  Immunohistochemical Analysis of Cerebral Thrombi Retrieved by Mechanical Thrombectomy from Patients with Acute Ischemic Stroke , 2016, International journal of molecular sciences.

[26]  Man-Seok Park,et al.  Histologic Analysis of Retrieved Clots in Acute Ischemic Stroke: Correlation with Stroke Etiology and Gradient-Echo MRI , 2015, American Journal of Neuroradiology.

[27]  W. Mali,et al.  Histopathologic Composition of Cerebral Thrombi of Acute Stroke Patients Is Correlated with Stroke Subtype and Thrombus Attenuation , 2014, PloS one.

[28]  K. Nakashima,et al.  [The Rotterdam study]. , 2011, Nihon rinsho. Japanese journal of clinical medicine.

[29]  C. Blomstrand,et al.  Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke , 2011, Journal of thrombosis and haemostasis : JTH.

[30]  A. Hofman,et al.  High von Willebrand Factor Levels Increase the Risk of Stroke: The Rotterdam Study , 2010, Stroke.

[31]  David Lee Gordon,et al.  Classification of Subtype of Acute Ischemic Stroke: Definitions for Use in a Multicenter Clinical Trial , 1993, Stroke.