Reverse effect of aspirin: Is the prothrombotic effect after aspirin discontinuation mediated by cyclooxygenase 2 inhibition?

被引:14
作者
Doutremepuich, Christian [1 ]
Aguejouf, Omar [1 ]
Eizayaga, Francisco X. [2 ]
Desplat, Vanessa [1 ]
机构
[1] Univ Victor Segalen Bordeaux 2, UFR Sci Pharmaceut, Hematol Lab, FR-33076 Bordeaux, France
[2] Univ Maimonides, Fac Med, CEBBAD, Buenos Aires, DF, Argentina
关键词
selective COX inhibitors; thrombosis; ultra-low-dose aspirin;
D O I
10.1159/000112638
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: While aspirin is the drug most often used to prevent cardiovascular complications, its discontinuation induces an increased risk of acute coronary syndrome and ischemic stroke in some patients. Objectives: We hypothesized that infinitesimal concentrations of aspirin could persist in plasma after its discontinuation, thereby inducing a prothrombotic effect that could be due to a modification in the mechanism of action of aspirin via the cyclooxygenase 1 (COX-1) and COX-2 pathways. Methods and Results: We studied the effects of ultra-low-dose aspirin (ULDA) as well as those of sc-560 and ns-398, specific COX-1 and COX-2 inhibitors, on induced hemorrhagic time and in a model of laser-induced thrombosis in rats. In the laser-induced thrombosis model, ULDA treatment increased the number of emboli and the duration of embolization, thereby confirming its prothrombotic effect described in previous publications. This effect was also observed in rats pretreated with sc-560 but not in those pretreated with ns-398. Conclusions: We demonstrated that ULDA induced a prothrombotic effect in the rats studied. This strongly suggests that a very small amount of aspirin could remain in the patient's blood after aspirin therapy, leading to cardiovascular complications. This effect may be mediated by the COX-2 pathway. Copyright (C) 2008 S. Karger AG, Basel.
引用
收藏
页码:40 / 44
页数:5
相关论文
共 15 条
[1]   Thromboembolic complications several days after a single-dose administration of aspirin [J].
Aguejouf, O ;
Belougne-Malfatti, E ;
Doutremepuich, F ;
Belon, P ;
Doutremepuich, C .
THROMBOSIS RESEARCH, 1998, 89 (03) :123-127
[2]   Effects of acetyl salicylic acid therapy on an experimental thrombosis induced by laser beam [J].
Aguejouf, O ;
Malfatti, E ;
Belon, P ;
Doutremepuich, C .
THROMBOSIS RESEARCH, 2000, 99 (06) :595-602
[3]   Cyclooxygenase inhibition and cardiovascular risk [J].
Antman, EM ;
DeMets, D ;
Loscalzo, J .
CIRCULATION, 2005, 112 (05) :759-770
[4]   Aspirin [J].
Awtry, EH ;
Loscalzo, J .
CIRCULATION, 2000, 101 (10) :1206-1218
[5]   A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50 279 patients at risk for coronary artery disease [J].
Biondi-Zoccai, Giuseppe G. L. ;
Lotrionte, Marzia ;
Agostoni, Pierfrancesco ;
Abbate, Antonio ;
Fusaro, Massimiliano ;
Burzotta, Francesco ;
Testa, Luca ;
Sheiban, Imad ;
Sangiorgi, Giuseppe .
EUROPEAN HEART JOURNAL, 2006, 27 (22) :2667-2674
[6]   Low-dose aspirin for secondary cardiovascular prevention -: cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation -: review and meta-analysis [J].
Burger, W ;
Chemnitius, JM ;
Kneissl, GD ;
Rücker, G .
JOURNAL OF INTERNAL MEDICINE, 2005, 257 (05) :399-414
[7]   Duration of increased bleeding tendency after cessation of aspirin therapy [J].
Cahill, RA ;
McGreal, GT ;
Crowe, BH ;
Ryan, DA ;
Manning, BJ ;
Cahill, MR ;
Redmond, HP .
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS, 2005, 200 (04) :564-573
[8]   Effect of Aspirin dose, preparation, and withdrawal on platelet response in normal volunteers [J].
Coleman, Jacqueline L. ;
Alberts, Mark J. .
AMERICAN JOURNAL OF CARDIOLOGY, 2006, 98 (06) :838-841
[9]   Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes [J].
Collet, JP ;
Montalescot, G ;
Blanchet, B ;
Tanguy, ML ;
Golmard, JL ;
Choussat, R ;
Beygui, F ;
Payot, L ;
Vignolles, N ;
Metzger, JP ;
Thomas, D .
CIRCULATION, 2004, 110 (16) :2361-2367
[10]  
DOUTREMEPUICH C, 1990, HAEMOSTASIS, V20, P99