Skip to main content
SpringerLink
Log in

Total burden of intraplaque hemorrhage in coronary arteries relates to the use of coumarin-type anticoagulants but not platelet aggregation inhibitors

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Intraplaque hemorrhage (IPH) is a crucial factor in progression and destabilization of an atherosclerotic plaque. Anti-thromboembolic drugs are widely used as prophylactic treatment against arterial and venous thrombotic diseases, but a major complication is bleeding. We investigated the association between exposure to anti-thromboembolic therapy and IPH in postmortem coronary arteries. Coronary arteries with postmortem angiographically confirmed extensive atherosclerosis were obtained at autopsy from patients who had received oral anticoagulants (n = 10), platelet aggregation inhibitors (n = 10), or no anti-thrombotic drugs (n = 10) before death. Coronary arteries were cut at 3-mm interval, and all plaque-containing segments were immunohistochemically screened for IPH and microvessels. These data were related to overall plaque composition and the use of anti-thromboembolic therapies. IPH was found in 483 out of 904 (53 %) coronary segments with advanced atherosclerotic plaques and more frequently in patients on oral anticoagulants (174/284, 61 %) than in patients on anti-platelets (198/376, 53 %) or without therapy (111/244, 46 %) (P = 0.02 and P = 0.001, respectively). Also, intraplaque microvascular leakage was more frequently observed in patients on anticoagulants than in non-treated patients (P = 0.03). Finally, the IPH appeared to be larger in plaques of patients on anticoagulant treatment (P < 0.001). Density of intraplaque microvessels was highest in plaques of patients on platelet inhibitors (P < 0.05), but this was not associated with increased hemorrhagic burden. Prophylactic therapy with oral coumarin-type anticoagulants appears to be associated with a higher hemorrhagic burden in atherosclerotic coronary arteries, which may lead to increase in plaque volume over time, in this selected subgroup of patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Davies MJ, Thomas AC (1985) Plaque fissuring–the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 53:363–373

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. van der Wal AC, Becker AE (1999) Atherosclerotic plaque rupture—pathologic basis of plaque stability and instability. Cardiovasc Res 41:334–344

    Article  PubMed  Google Scholar 

  3. Wartman W (1938) Occlusion of the coronary arteries by hemorrhage into their walls. Am Heart J 15:459–470

    Article  Google Scholar 

  4. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM (2000) Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 20:1262–1275

    Article  CAS  PubMed  Google Scholar 

  5. Kolodgie FD, Gold HK, Burke AP, Fowler DR, Kruth HS, Weber DK, Farb A, Guerrero LJ, Hayase M, Kutys R, Narula J, Finn AV, Virmani R (2003) Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med 349:2316–2325

    Article  CAS  PubMed  Google Scholar 

  6. Takaya N, Yuan C, Chu B, Saam T, Polissar NL, Jarvik GP, Isaac C, McDonough J, Natiello C, Small R, Ferguson MS, Hatsukami TS (2005) Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study. Circulation 111:2768–2775

    Article  PubMed  Google Scholar 

  7. Davies MJ (2000) The pathophysiology of acute coronary syndromes. Heart 83:361–366

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Kockx MM, Cromheeke KM, Knaapen MW, Bosmans JM, De Meyer GR, Herman AG, Bult H (2003) Phagocytosis and macrophage activation associated with hemorrhagic microvessels in human atherosclerosis. Arterioscler Thromb Vasc Biol 23:440–446

    Article  CAS  PubMed  Google Scholar 

  9. Lin HL, Xu XS, Lu HX, Zhang L, Li CJ, Tang MX, Sun HW, Liu Y, Zhang Y (2007) Pathological mechanisms and dose dependency of erythrocyte-induced vulnerability of atherosclerotic plaques. J Mol Cell Cardiol 43:272–280

    Article  CAS  PubMed  Google Scholar 

  10. Furie B, Furie BC (2008) Mechanisms of thrombus formation. N Engl J Med 359:938–949

    Article  CAS  PubMed  Google Scholar 

  11. Mackman N (2008) Triggers, targets and treatments for thrombosis. Nature 451:914–918

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Bousser MG, Eschwege E, Haguenau M, Lefaucconnier JM, Thibult N, Touboul D, Touboul PJ (1983) “AICLA” controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Stroke 14:5–14

    Article  CAS  PubMed  Google Scholar 

  13. Baigent C, Collins R, Appleby P, Parish S, Sleight P, Peto R (1998) ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither. The ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. BMJ 316:1337–1343

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Hirsh J (1991) Oral anticoagulant drugs. N Engl J Med 324:1865–1875

    Article  CAS  PubMed  Google Scholar 

  15. Nobuyoshi M, Tanaka M, Nosaka H, Kimura T, Yokoi H, Hamasaki N, Kim K, Shindo T, Kimura K (1991) Progression of coronary atherosclerosis: is coronary spasm related to progression? J Am Coll Cardiol 18:904–910

    Article  CAS  PubMed  Google Scholar 

  16. Landefeld CS, Beyth RJ (1993) Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. Am J Med 95:315–328

    Article  CAS  PubMed  Google Scholar 

  17. Serebruany VL, Malinin AI, Eisert RM, Sane DC (2004) Risk of bleeding complications with antiplatelet agents: meta-analysis of 338,191 patients enrolled in 50 randomized controlled trials. Am J Hematol 75:40–47

    Article  CAS  PubMed  Google Scholar 

  18. Wolff T, Miller T, Ko S (2009) Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 150:405–410

    Article  PubMed  Google Scholar 

  19. Derksen WJ, Peeters W, Tersteeg C, de Vries JP, de Kleijn DP, Moll FL, van der Wal AC, Pasterkamp G, Vink A (2011) Age and coumarin-type anticoagulation are associated with the occurrence of intraplaque hemorrhage, while statins are associated less with intraplaque hemorrhage: a large histopathological study in carotid and femoral plaques. Atherosclerosis 214:139–143

    Article  CAS  PubMed  Google Scholar 

  20. DeVito CL, Little WA (1988) Fractal sets associated with functions: the spectral lines of hydrogen. Phys Rev A 38:6362–6364

    Article  PubMed  Google Scholar 

  21. Arbustini E, Morbini P, D’Armini AM, Repetto A, Minzioni G, Piovella F, Vigano M, Tavazzi L (2002) Plaque composition in plexogenic and thromboembolic pulmonary hypertension: the critical role of thrombotic material in pultaceous core formation. Heart 88:177–182

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Meijer-Jorna LB, Mekkes JR, van der Wal AC (2002) Platelet involvement in cutaneous small vessel vasculitis. J Cutan Pathol 29:176–180

    Article  PubMed  Google Scholar 

  23. Virmani R, Kolodgie FD, Burke AP, Finn AV, Gold HK, Tulenko TN, Wrenn SP, Narula J (2005) Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol 25:2054–2061

    Article  CAS  PubMed  Google Scholar 

  24. Ammar AD, Wilson RL, Travers H, Lin JJ, Farha SJ, Chang FC (1984) Intraplaque hemorrhage: its significance in cerebrovascular disease. Am J Surg 148:840–843

    Article  CAS  PubMed  Google Scholar 

  25. Jorgensen L, Chandler AB, Borchgrevink CF (1971) Acute lesions of coronary arteries in anticoagulant-treated and in untreated patients. Atherosclerosis 13:21–44

    Article  CAS  PubMed  Google Scholar 

  26. Fisher M, Sacoolidge JC, Taylor CR (1987) Patterns of fibrin deposits in carotid artery plaques. Angiology 38:393–399

    Article  CAS  PubMed  Google Scholar 

  27. Ernst RL, Ammar AD, Lin JJ, Travers H (1986) The effect of antiplatelet therapy on the incidence of carotid plaque hemorrhage. Stroke 17:540–541

    Article  CAS  PubMed  Google Scholar 

  28. AbuRahma AF, Boland JP, Robinson P, Decanio R (1990) Antiplatelet therapy and carotid plaque hemorrhage and its clinical implications. J Cardiovasc Surg (Torino) 31:66–70

    CAS  Google Scholar 

  29. Glagov S, Zarins C, Giddens DP, Ku DN (1988) Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Arch Pathol Lab Med 112:1018–1031

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study is supported by the Netherlands Heart Foundation.

Authors’ contribution

XL, RJW, and ACW are responsible for the conception and design of the study. XL, AV, JK, OB, HJP, JGPT, and ACW are responsible for the acquisition of data or analysis and interpretation of data. XL, AV, HNJP, RW, and ACW are responsible for drafting the article or revising it critically for important intellectual content. XL and ACW are responsible for the final approval of the version published. ACW and XL are responsible for the overall content.

Conflict of interest

No competing interest.

Author information

Authors and Affiliations

  1. Department of Pathology, Academic Medical Center, University of Amsterdam, Room M2-129, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Xiaofei Li, Jesper Kers, Onno J. de Boer, Hanneke J. P. Ploegmakers & Allard C. van der Wal

  2. Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Jan G. P. Tijssen & Robbert J. de Winter

  3. Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Aryan Vink

  4. Departments of Pathology, VU University Medical Center, VU university of Amsterdam, Amsterdam, The Netherlands

    Hans W. M. Niessen

Authors
  1. Xiaofei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aryan Vink
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans W. M. Niessen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jesper Kers
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Onno J. de Boer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hanneke J. P. Ploegmakers
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jan G. P. Tijssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Robbert J. de Winter
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Allard C. van der Wal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Allard C. van der Wal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Vink, A., Niessen, H.W.M. et al. Total burden of intraplaque hemorrhage in coronary arteries relates to the use of coumarin-type anticoagulants but not platelet aggregation inhibitors. Virchows Arch 465, 723–729 (2014). https://doi.org/10.1007/s00428-014-1654-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-014-1654-y

Keywords

Search

Navigation