Clinical Neuroradiology

, Volume 26, Issue 2, pp 189–197 | Cite as

The Impact of Histological Clot Composition in Embolic Stroke

  • T. Boeckh-Behrens
  • M. Schubert
  • A. Förschler
  • S. Prothmann
  • K. Kreiser
  • C. Zimmer
  • J. Riegger
  • J. Bauer
  • F. Neff
  • V. Kehl
  • J. Pelisek
  • L. Schirmer
  • M. Mehr
  • H. Poppert
Original Article

Abstract

Purpose

Thrombus composition has been suggested to have a decisive impact on the outcome of patients treated by mechanical thrombectomy because of embolic stroke. The recent development of stent retrievers allows collection and, hence, histopathological analysis of fresh thrombus material. Against this background, the aim of this prospective study was to assess the impact of thrombus composition on mechanical recanalization, clinical outcome and stroke etiology.

Methods

Thirty-four patients suffering from acute ischemic stroke due to occlusion of the distal internal carotid artery/carotid-T, anterior cerebral artery, or middle cerebral arteries were mechanically recanalized, and thrombus material was obtained. Histological thrombus composition was compared with imaging, clinical, and neurointerventional data.

Results

The main findings were that a higher percentage of white blood cells (WBCs) in the thrombus was associated with (i) cardioembolic etiology, (ii) extended mechanical recanalization time, and (iii) less favorable recanalization (Thrombolysis in Cerebral Infarction score) and clinical outcome (National Institute of Health Stroke Scale).

Conclusion

Our results suggest that thrombi with a high WBC fraction are related to more organized thrombi of cardioembolic origin associated with less favorable recanalization and clinical outcome in acute ischemic anterior circulation stroke. WBC-mediated immunological and coagulatory processes may play a key role in thrombus formation and pathogenesis of stroke warranting further investigation.

Keywords

Histopathology Mechanical recanalization Stroke Thrombus 

Supplementary material

62_2014_347_MOESM1_ESM.pdf (460 kb)
(PDF 460 kb)

References

  1. 1.
    Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke. 2007;38:967–73.CrossRefPubMedGoogle Scholar
  2. 2.
    Alexandrov AV. Current and future recanalization strategies for acute ischemic stroke. J Intern Med. 2010;267:209–19.CrossRefPubMedGoogle Scholar
  3. 3.
    Brekenfeld C, Gralla J, Zubler C, Schroth G. Mechanical thrombectomy for acute ischemic stroke. Rofo. 2012;184:503–12.CrossRefPubMedGoogle Scholar
  4. 4.
    Roth C, Papanagiotou P, Behnke S, Walter S, Haass A, Becker C, Fassbender K, Politi M, Körner H, Romann MS, Reith W. Stent-assisted mechanical recanalization for treatment of acute intracerebral artery occlusions. Stroke. 2010;41:2559–67.CrossRefPubMedGoogle Scholar
  5. 5.
    Marder VJ, Chute DJ, Starkman S, Abolian AM, Kidwell C, Liebeskind D, Ovbiagele B, Vinuela F, Duckwiler G, Jahan R, Vespa PM, Selco S, Rajajee V, Kim D, Sanossian N, Saver JL. Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke. Stroke. 2006;37:2086–93.CrossRefPubMedGoogle Scholar
  6. 6.
    Liebeskind DS, Sanossian N, Yong WH, Starkman S, Tsang MP, Moya AL, Zheng DD, Abolian AM, Kim D, Ali LK, Shah SH, Towfighi A, Ovbiagele B, Kidwell CS, Tateshima S, Jahan R, Duckwiler GR, Viñuela F, Salamon N, Villablanca JP, Vinters HV, Marder VJ, Saver JL. CT and MRI early vessel signs reflect clot composition in acute stroke. Stroke. 2011;42:1237–43.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Jang IK, Gold HK, Ziskind AA, Fallon JT, Holt RE, Leinbach RC, May JW, Collen D. Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. A possible explanation for resistance to coronary thrombolysis. Circulation. 1989;79:920–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Kirchhof K, Sikinger M, Welzel T, Zoubaa S, Sartor K. Does the result of thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in rabbits depend on the erythrocyte- and fibrin-content of a thrombus? Rofo. 2004;176:98–105.CrossRefPubMedGoogle Scholar
  9. 9.
    Molina CA. Imaging the clot: does clot appearance predict the efficacy of thrombolysis? Stroke. 2005;36:2333–4.CrossRefPubMedGoogle Scholar
  10. 10.
    Riedel CH, Zimmermann P, Jensen-Kondering U, Stingele R, Deuschl G, Jansen O. The importance of size: successful recanalization by intravenous thrombolysis in acute anterior stroke depends on thrombus length. Stroke. 2011;42:1775–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Almekhlafi MA, Hu WY, Hill MD, Auer RN. Calcification and endothelialization of thrombi in acute stroke. Ann Neurol. 2008;64:344–348.CrossRefPubMedGoogle Scholar
  12. 12.
    Adams HP, Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE, 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Ischemic Stroke Treatment. Stroke. 1993;24:35–41.CrossRefPubMedGoogle Scholar
  13. 13.
    Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, Dillon W, Warach S, Broderick J, Tilley B, Sacks D, Technology Assessment Committee of the American Society of Interventional and Therapeutic Neuroradiology, Technology Assessment Committee of the Society of Interventional Radiology. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke. 2003;34:e109–37.CrossRefPubMedGoogle Scholar
  14. 14.
    French JE. The structure of natural and experimental thrombi. Ann R Coll Surg Engl. 1965;36:191–200.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Welch WH. The structure of white thrombi. Trans Path Soc Philadelphia. 1887;13:281.Google Scholar
  16. 16.
    Yuki I, Kan I, Vinters HV, Kim RH, Golshan A, Vinuela FA, Sayre JW, Murayama Y, Vinuela F. The impact of thromboemboli histology on the performance of a mechanical thrombectomy device. AJNR Am J Neuroradiol. 2012;33:643–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Nardi K, Milia P, Eusebi P, Paciaroni M, Caso V, Agnelli G. Admission leukocytosis in acute cerebral ischemia: influence on early outcome. J Stroke Cerebrovasc Dis. 2012;21:819–24.CrossRefPubMedGoogle Scholar
  18. 18.
    Akopov SE, Simonian NA, Grigorian GS. Dynamics of polymorphonuclear leukocyte accumulation in acute cerebral infarction and their correlation with brain tissue damage. Stroke. 1996;27:1739–43.CrossRefPubMedGoogle Scholar
  19. 19.
    Gelderblom M, Leypoldt F, Steinbach K, Behrens D, Choe CU, Siler DA, Arumugam TV, Orthey E, Gerloff C, Tolosa E, Magnus T. Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke. 2009;40:1849–57.CrossRefPubMedGoogle Scholar
  20. 20.
    Akopov SE, Grigorian GS, Ovanessian GA. Deactivation of NO polymorphonuclear leukocytes in patients with ischemic cerebral infarction. Stroke. 1996;27:2337–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Connolly ES, Jr., Winfree CJ, Springer TA, Naka Y, Liao H, Yan SD, Stern DM, Solomon RA, Gutierrez-Ramos JC, Pinsky DJ. Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke. J Clin Invest. 1996;97:209–16.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kleinschnitz C, De Meyer SF, Schwarz T, Austinat M, Vanhoorelbeke K, Nieswandt B, Deckmyn H, Stoll G. Deficiency of von Willebrand factor protects mice from ischemic stroke. Blood. 2009;113:3600–3.CrossRefPubMedGoogle Scholar
  23. 23.
    Soriano SS, Coxon A, Wang AF, Frosch MP, Lipton SA, Hickey PR, Mayadas TN. Mice deficient in Mac-1 (CD11b/CD18) are less susceptible to cerebralischemia/reperfusion injury. Stroke. 1999;30:134–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Stoll G, Kleinschnitz C, Nieswandt B. Combating innate inflammation: a new paradigm for acute treatment of stroke? Ann N Y Acad Sci. 2010;1207:149–54.CrossRefPubMedGoogle Scholar
  25. 25.
    Akopov S, Sercombe R, Seylaz J. Cerebrovascular reactivity: role of endothelium/platelet/leukocyte interactions. Cerebrovasc Brain Metab Rev. 1996;27:11–94.Google Scholar
  26. 26.
    Granger DN, Kubes P. The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion. J Leukoc Biol. 1994;55:662–75.PubMedGoogle Scholar
  27. 27.
    Kochanek PM, Hallenbeck JM. Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke. 1992;23:1367–79.CrossRefPubMedGoogle Scholar
  28. 28.
    Mullane K. Neutrophil and endothelial changes in reperfusion injury. Trends Cardiovasc Med. 1991;1:282–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Hallenbeck JM, Dutka AJ. Background review and current concepts of reperfusion injury. Arch Neurol. 1990;47:1245–54.CrossRefPubMedGoogle Scholar
  30. 30.
    Massberg S, Grahl L, von Bruehl ML, Manukyan D, Pfeiler S, Goosmann C, Brinkmann V, Lorenz M, Bidzhekov K, Khandagale AB, Konrad I, Kennerknecht E, Reges K, Holdenrieder S, Braun S, Reinhardt C, Spannagl M, Preissner KT, Engelmann B. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. 2010;16:887–96.CrossRefPubMedGoogle Scholar
  31. 31.
    Gavins FN. Modeling inflammation and microvascular dysfunction. Ann N Y Acad Sci. 2011;1245:34–5.CrossRefPubMedGoogle Scholar
  32. 32.
    Simons N, Mitchell P, Dowling R, Gonzales M, Yan B. Thrombus composition in acute ischemic stroke: a histopathological study of thrombus extracted by endovascular retrieval. J Neuroradiol. 2014 Feb. 20. pii: S0150-9861(14)00128-X. Epub ahead of print.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • T. Boeckh-Behrens
    • 1
  • M. Schubert
    • 1
  • A. Förschler
    • 1
  • S. Prothmann
    • 1
  • K. Kreiser
    • 1
  • C. Zimmer
    • 1
  • J. Riegger
    • 2
  • J. Bauer
    • 1
  • F. Neff
    • 3
  • V. Kehl
    • 4
  • J. Pelisek
    • 5
  • L. Schirmer
    • 6
  • M. Mehr
    • 6
  • H. Poppert
    • 6
  1. 1.Department of NeuroradiologyUniversity Hospital Rechts der Isar, Technical University MunichMunichGermany
  2. 2.Department of Experimental CardiologyGerman Heart Centre MunichMunichGermany
  3. 3.Department of PathologyGerman Research Centre for Environmental HealthMunichGermany
  4. 4.Institute of Medical Statistics and EpidemiologyUniversity Hospital Rechts der Isar, Technical University MunichMunichGermany
  5. 5.Clinic of Vascular and Endovascular SurgeryUniversity Hospital Rechts der Isar, Technical University MunichMunichGermany
  6. 6.Department of NeurologyUniversity Hospital Rechts der Isar, Technical University MunichMunichGermany

Personalised recommendations