Reverse Effect of Aspirin: Is the Prothrombotic Effect after Aspirin Discontinuation Mediated by Cyclooxygenase 2 Inhibition?Doutremepuich C.a · Aguejouf O.a · Eizayaga F.X.b · Desplat V.a
aLaboratoire d’Hématologie, UFR des Sciences Pharmaceutiques, Université Victor Segalen Bordeaux 2, Bordeaux, France; bCEBBAD, Facultad de Medicina, Universidad Maimónides, Buenos Aires, Argentina
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
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.
© 2008 S. Karger AG, Basel
- Awtry EH, Loscalzo J: Aspirin. Circulation 2000;101:1206–1218.
- Sibon I, Orgogozo JM: Antiplatelet drug discontinuation is a risk factor for ischemic stroke. Neurology 2004;62:1187–1189.
- Fisher LM, Schlienger RG, Matter CM, Jick HJ, Meier CR: Discontinuation of nonsteroidal anti-inflammatory drug therapy and risk of acute myocardial infarction. Arch Intern Med 2004;164:2472–2476.
- Mc Fadden EP, Stabile E, Regar E, Cheneau E, Ong AT, Kinnaird T, Suddath WO, Weissman NJ, Torguson R, Kent KM, Pichard AD, Satler LF, Waksman R, Serruys PW: Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 2004;364:1519–1521.
- Collet JP, Montalescot G, Blanchet B, Tanguy ML, Golmard JL, Choussat R, Beygui F, Payot L, Vignolles N, Metzger JP, Thomas D: Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes. Circulation 2004;110:2361–2367.
- Ferrari E, Benhamou M, Cerboni P, Marcel B: Coronary syndromes following aspirin withdrawal: a special risk for late stent thrombosis. J Am Coll Cardiol 2005;45:456–459.
- Cahill RA, McGreal GT, Crowe BH, Ryan DA, Manning BJ, Cahill MR, Redmond HP: Duration of increased bleeding tendency after cessation of aspirin therapy. J Am Coll Surg 2005;200:564–573.
- Burger W, Chemnitius JM, Kneissl GD, Rücker G: Low-dose aspirin for secondary cardiovascular prevention – cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation – review and meta-analysis. J Intern Med 2005;257:399–414.
- Biondi-Zoccai GG, Lotrionte M, Agostoni P, Abbate A, Fusaro M, Burzotta F, Testa L, Sheiban I, Sangiorgi G: 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. Eur Heart J 2006;27:2667–2674.
- Aguejouf O, Belougne-Malfatti E, Doutremepuich F, Belon P, Doutremepuich C: Thromboembolic complications several days after a single-dose administration of aspirin. Thromb Res 1998;89:123–127.
- Aguejouf O, Malfatti E, Belon P, Doutremepuich C: Effects of acetyl salicylic acid therapy on an experimental thrombosis induced by laser beam. Thromb Res 2000;99:595–602.
- Doutremepuich C, de Seze O, Le Roy D, Lalanne MC, Anne MC: Aspirin at very ultra low dosage in healthy volunteers: effects on bleeding time, platelet aggregation and coagulation. Haemostasis 1990;20:99–105.
Fries S, Grosser T: The cardiovascular pharmacology of COX-2 inhibition. Hematology Am Soc Hematol Educ Program 2005;1: 445–451.
- Antman EM, DeMets D, Loscalzo J: Cyclooxygenase inhibition and cardiovascular risk. Circulation 2005;112:759–770.
- Coleman JL, Alberts MJ: Effect of aspirin dose, preparation, and withdrawal on platelet response in normal volunteers. Am J Cardiol 2006;98:838–841.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.