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Original research
Correlation of von Willebrand factor and platelets with acute ischemic stroke etiology and revascularization outcome: an immunohistochemical study
  1. Oana Madalina Mereuta1,
  2. Mehdi Abbasi1,
  3. Jorge L Arturo Larco1,2,
  4. Daying Dai1,
  5. Yang Liu1,
  6. Santhosh Arul1,
  7. Ramanathan Kadirvel1,
  8. Ricardo A Hanel3,
  9. Albert J Yoo4,
  10. Mohammed A Almekhlafi5,
  11. Kennith F Layton6,
  12. Josser E Delgado Almandoz7,
  13. Peter Kvamme8,
  14. Vitor Mendes Pereira9,
  15. Babak S Jahromi10,
  16. Raul G Nogueira11,12,
  17. Matthew J Gounis13,
  18. Biraj Patel14,
  19. Amin Aghaebrahim3,
  20. Eric Sauvageau3,
  21. Parita Bhuva4,
  22. Jazba Soomro4,
  23. Andrew M Demchuk5,
  24. Ike C Thacker6,
  25. Yasha Kayan7,
  26. Alexander Copelan7,
  27. Pouya Nazari10,
  28. Donald Robert Cantrell10,
  29. Diogo C Haussen11,12,
  30. Alhamza R Al-Bayati11,12,
  31. Mahmoud Mohammaden11,12,
  32. Leonardo Pisani11,12,
  33. Gabriel Martins Rodrigues11,12,
  34. Ajit S Puri13,
  35. John Entwistle14,
  36. Alexander Meves15,
  37. Luis Savastano2,
  38. Harry J Cloft1,
  39. Shahid M Nimjee16,
  40. Robert D McBane II17,
  41. David F Kallmes1,
  42. Waleed Brinjikji1,2
  1. 1Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota, USA
  3. 3Department of Neurosurgery, Baptist Medical Center, Jacksonville, Florida, USA
  4. 4Department of Neurointervention, Texas Stroke Institute, Dallas-Fort Worth, Texas, USA
  5. 5Departments of Clinical Neurosciences, Radiology and Community Health Sciences, Hotchkiss Brain Institute and Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  6. 6Department of Radiology, Baylor University Medical Center, Dallas, Texas, USA
  7. 7Department of NeuroInterventional Radiology, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA
  8. 8Department of Radiology, University of Tennessee Medical Center, Knoxville, Tennessee, USA
  9. 9Departments of Medical Imaging and Surgery, Toronto Western Hospital, Toronto, Ontario, Canada
  10. 10Departments of Radiology and Neurosurgery, Northwestern University, Chicago, Illinois, USA
  11. 11Department of Neurology, Emory University, Atlanta, Georgia, USA
  12. 12Grady Memorial Hospital, Atlanta, Georgia, USA
  13. 13Department of Radiology, University of Massachusetts Medical School, New England Center for Stroke Research, Worcester, Massachusetts, USA
  14. 14Departments of Radiology and Neurosurgery, Carilion Clinic, Roanoke, Virginia, USA
  15. 15Department of Dermatology, Mayo Clinic, Rochester, Minnesota, USA
  16. 16Department of Neurological Surgery, Ohio State University, Columbus, Ohio, USA
  17. 17Gonda Vascular Center, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr Oana Madalina Mereuta, Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA; mereuta.oana{at}mayo.edu

Abstract

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.

  • Stroke
  • Thrombectomy
  • Embolic
  • Platelets

Data availability statement

Data are available upon reasonable request. Data are available from the corresponding author upon reasonable request.

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Data availability statement

Data are available upon reasonable request. Data are available from the corresponding author upon reasonable request.

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Footnotes

  • Twitter @AlmekhlafiMa, @VitorMendesPer1, @PouyaNazari5, @diogohaussen, @pisanileonardo, @AjitSPuri1

  • Contributors OMM and WB were involved in all stages of the study from concept design to drafting the manuscript. WB is also acting as guarantor for this manuscript. MA, JLAL, DD, YL, SA and RK were responsible for collecting and recording the clinical and procedural information from patients and were involved in the histological analysis of clots. This study is the result of a multicenter registry requiring the collaboration of multiple neurointerventionalists, research fellows and histopathologists and all authors meet the ICJME criteria for authorship. All authors reviewed, edited and approved the final manuscript prior to submission.

  • Funding This work was supported by the National Institutes of Health (R01 NS105853).

  • Competing interests RK reports NIH funding (R01 NS076491, R43 NS110114 and R44 NS107111), is a research consultant for Cerenovus, Insera Therapeutics, Marblehead Medical, Microvention, MIVI Neuroscience, Neurogami Medical and Triticum, and has stock in Neurosigma (money paid to institution). AJY receives research support from Medtronic, Cerenovus, Penumbra and Stryker, and is a consultant for Penumbra, Cerenovus, Zoll Circulation and Vesalio. He is on the Scientific Advisory Board of XCath and Nico-lab, and has equity interest in Insera Therapeutics. JEDA declares competing interests in the form of employment (modest compensation) from Medtronic and Penumbra. AMD received honoraria from Medtronic for Continuing Medical Education events. RGN declares competing interests in the form of Stryker (DAWN Trial (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With TREVO) Principal Investigator, no compensation; TREVO Registry Steering Committee, no compensation; TREVO-2 Trial Principal Investigator, modest compensation; consultant, modest compensation), Medtronic (SWIFT Trial (Solitaire With the Intention for Thrombectomy) Steering Committee, modest compensation; SWIFT-Prime Trial Steering Committee, no compensation; STAR Trial (Solitaire FR Thrombectomy for Acute Revascularisation) Angiographic Core Lab, significant compensation), Penumbra (no compensation), Cerenovus/Neuravi (ENDOLOW Trial Principal Investigator, EXCELLENT Registry Principal Investigator, ARISE-2 Trial (Analysis of Revascularization in Ischemic Stroke With EmboTrap) Steering Committee, no compensation; Physician Advisory Board, modest compensation), Phenox (Physician Advisory Board, modest compensation), Anaconda (Physician Advisory Board, modest compensation), Genentech (Physician Advisory Board, modest compensation), Biogen (Physician Advisory Board, modest compensation), Prolong Pharmaceuticals (Physician Advisory Board, modest compensation), IschemaView (Speaker, modest compensation), Brainomix (Research Software Use, no compensation), Sensome (Research Device Use, no compensation), Viz-AI (Physician Advisory Board, stock options), Philips (Research Software Use, no compensation; Speaker, modest compensation), and Corindus Vascular Robotics (Physician Advisory Board, stock options). DFK is President of Marblehead Medical and has a patent pending in balloon catheter technologies, and receives research support from Cerenovus, Insera Therapeutics, Medtronic, MicroVention, MIVI Neuroscience, NeuroSave, Neurogami Medical, Sequent Medical and Insera, and has stock in Neurosigma (money paid to institution). He is on the Scientific Advisory Board of Triticum and previously served on a SAB for Boston Scientific. WB is CMO of Marblehead Medical and has a patent pending in balloon catheter technologies, and he is a consultant for Cerenovus and Microvention. He reports NIH funding (R01 NS105853). MJG is a member of the JNIS Editorial Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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