Virchows Archiv

, Volume 465, Issue 6, pp 723–729 | Cite as

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

  • Xiaofei Li
  • Aryan Vink
  • Hans W. M. Niessen
  • Jesper Kers
  • Onno J. de Boer
  • Hanneke J. P. Ploegmakers
  • Jan G. P. Tijssen
  • Robbert J. de Winter
  • Allard C. van der WalEmail author
Original Article


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.


Coronary artery Atherosclerotic plaque Hemorrhage Anticoagulant Platelet aggregation inhibitors 



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.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Xiaofei Li
    • 1
  • Aryan Vink
    • 3
  • Hans W. M. Niessen
    • 4
  • Jesper Kers
    • 1
  • Onno J. de Boer
    • 1
  • Hanneke J. P. Ploegmakers
    • 1
  • Jan G. P. Tijssen
    • 2
  • Robbert J. de Winter
    • 2
  • Allard C. van der Wal
    • 1
    Email author
  1. 1.Department of Pathology, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Department of Cardiology, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  3. 3.Department of Pathology, University Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands
  4. 4.Departments of Pathology, VU University Medical CenterVU university of AmsterdamAmsterdamThe Netherlands

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