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Original research
Per-pass analysis of acute ischemic stroke clots: impact of stroke etiology on extracted clot area and histological composition
  1. Seán Fitzgerald1,
  2. Rosanna Rossi1,2,
  3. Oana Madalina Mereuta1,2,
  4. Duaa Jabrah1,
  5. Adaobi Okolo1,
  6. Andrew Douglas1,2,
  7. Sara Molina Gil1,2,
  8. Abhay Pandit2,
  9. Ray McCarthy3,
  10. Michael Gilvarry3,
  11. Dennis Dunker4,5,
  12. Annika Nordanstig6,7,
  13. Erik Ceder4,5,
  14. Petra Redfors6,7,
  15. Katarina Jood6,7,
  16. Niclas Dehlfors4,5,
  17. Georgios Magoufis8,
  18. Georgios Tsivgoulis9,
  19. Waleed Brinjikji10,
  20. David F Kallmes10,
  21. Alan O'Hare11,
  22. Sarah Power11,
  23. Paul Brennan11,
  24. Jack Alderson11,
  25. András Nagy12,
  26. Ágnes Vadász12,
  27. Klearchos Psychogios8,9,
  28. Istvan Szikora12,
  29. Turgut Tatlisumak6,7,
  30. Alexandros Rentzos4,5,
  31. John Thornton11,
  32. Karen M Doyle1,2
  1. 1Department of Physiology, National University of Ireland Galway, Galway, Ireland
  2. 2CÚRAM - SFI Centre for Research in Medical Devices, National University of Ireland Galway, Galway, Ireland
  3. 3Cerenovus, Galway Neuro Technology Centre, Johnson and Johnson Medical Devices, Galway, Ireland
  4. 4Department of Interventional and Diagnostic Neuroradiology, Sahlgrenska University Hospital, Göteborg, Sweden
  5. 5Department of Radiology, University of Gothenburg Institute of Clinical Sciences, Göteborg, Sweden
  6. 6Department of Neurology, Sahlgrenska University Hospital, Göteborg, Sweden
  7. 7Department of Clinical Neuroscience, University of Gothenburg Institute of Neuroscience and Physiology, Göteborg, Sweden
  8. 8Department of Interventional Neuroradiology, Metropolitan Hospital Athens, Piraeus, Greece
  9. 9Second Department of Neurology, “Attikon” Hospital, School of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
  10. 10Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
  11. 11Interventional Neuroradiology Service, Department of Radiology, Beaumont Hospital, Dublin, Ireland
  12. 12Department of Neurointerventions, National Institute of Clinical Neurosciences, Budapest, Hungary
  1. Correspondence to Dr Karen M Doyle, Department of Physiology, National University of Ireland Galway, Galway, Ireland; karen.doyle{at}nuigalway.ie

Abstract

Background Initial studies investigating correlations between stroke etiology and clot composition are conflicting and do not account for clot size as determined by area. Radiological studies have shown that cardioembolic strokes are associated with shorter clot lengths and lower clot burden than non-cardioembolic clots.

Objective To report the relationship between stroke etiology, extracted clot area, and histological composition at each procedural pass.

Methods As part of the multi-institutional RESTORE Registry, the Martius Scarlett Blue stained histological composition and extracted clot area of 612 per-pass clots retrieved from 441 patients during mechanical thrombectomy procedures were quantified. Correlations with clinical and procedural details were investigated.

Results Clot composition varied significantly with procedural passes; clots retrieved in earlier passes had higher red blood cell content (H4=11.644, p=0.020) and larger extracted clot area (H4=10.730, p=0.030). Later passes were associated with significantly higher fibrin (H4=12.935, p=0.012) and platelets/other (H4=15.977, p=0.003) content and smaller extracted clot area. Large artery atherosclerotic (LAA) clots were significantly larger in the extracted clot area and more red blood cell-rich than other etiologies in passes 1–3. Cardioembolic and cryptogenic clots had similar histological composition and extracted clot area across all procedural passes.

Conclusion LAA clots are larger and associated with a large red blood cell-rich extracted clot area, suggesting soft thrombus material. Cardioembolic clots are smaller in the extracted clot area, consistent in composition and area across passes, and have higher fibrin and platelets/other content than LAA clots, making them stiffer clots. The per-pass histological composition and extracted clot area of cryptogenic clots are similar to those of cardioembolic clots, suggesting similar formation mechanisms.

  • thrombectomy
  • atherosclerosis
  • intervention
  • stroke
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Footnotes

  • Twitter @FitzSeanT

  • Contributors SF, IS, TT, AR, JT, and KD, were involved in all stages of the manuscript from concept design to drafting the manuscript. All other authors participated in various aspects of the project and reviewed and edited the manuscript prior to submission. AP, RM, MG, WB, DFK, and GT were involved in the study design and data interpretation. RR, OMM, DJ, AO, AD, and SMG performed the experiments and analysis described, including measurement of the extracted clot area, histological staining, and quantification of the cases and statistical analysis. DD, ANo, EC, PR, KJ, ND, GM, AO, SP, PB, JA, ANa, AV, and KP, collected clot samples and extracted corresponding clinical data for each patient at each of their respective participating hospitals.

  • Funding This work was supported by the European Regional Development Fund and Science Foundation Ireland grant number (13/RC/2073) and by the National Institutes of Health grant number (R01 NS105853).

  • Competing interests The authors declare competing interests (funding, employment or personal financial interests) in relation to the work described herein. KD received research funding support from Science Foundation Ireland that is co-funded by Cerenovus.

  • Patient consent for publication Not required.

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

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

  • 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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