title: Total burden of intraplaque hemorrhage in coronary arteries relates to the use of coumarin-type anticoagulants but not platelet aggregation inhibitors.
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.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Room M2-129, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.forename: Jesper
authors.initials: J
authors.lastname: Kers
authors.forename: Onno J
authors.initials: OJ
authors.lastname: de Boer
authors.forename: Hanneke J P
authors.initials: HJ
authors.lastname: Ploegmakers
authors.forename: Jan G P
authors.initials: JG
authors.lastname: Tijssen
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: de Winter
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects*; D001344:Autopsy; D003324:Coronary Artery Disease / Q000473:pathology*; D003328:Coronary Thrombosis / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology*; D003374:Coumarins / Q000009:adverse effects*; D005260:Female; D006470:Hemorrhage; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D003374:Coumarins; D010975:Platelet Aggregation Inhibitors; C030123:coumarin