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(Circulation. 2003;108:542.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Functional and Biochemical Evaluation of Platelet Aspirin Resistance After Coronary Artery Bypass Surgery

N. Zimmermann, MD; A. Wenk, BSc; U. Kim, BSc; P. Kienzle, BSc; A.-A. Weber, MD; E. Gams, MD; K. Schrör, MD; T. Hohlfeld, MD

From the Institut für Pharmakologie und Klinische Pharmakologie (A.W., U.K., P.K., A.-A.W., K.S., T.H.) and Klinik für Thorax- und Kardiovaskuläre Chirurgie (N.Z., E.G.), UniversitätsKlinikum, Heinrich Heine-Universität Düsseldorf, Germany.

Correspondence to K. Schrör, MD, Institut für Pharmakologie und Klinische Pharmakologie, UniversitätsKlinikum, Heinrich Heine-Universität, Moorenstraße 5, 40225 Düsseldorf, Germany. E-mail kschroer{at}uni-duesseldorf.de

Received September 4, 2002; de novo received February 13, 2003; revision received May 6, 2003; accepted May 7, 2003.

Background— Aspirin inhibits platelet activation and reduces atherothrombotic complications in patients at risk of myocardial infarction and stroke. However, a sufficient inhibition of platelet function by aspirin is not always achieved. The causes of this aspirin resistance are unknown.

Methods and Results— Patients undergoing coronary artery bypass grafting (CABG) have a high incidence of aspirin resistance. To evaluate functional and biochemical responses to aspirin, platelet-rich plasma was obtained before and at days 1, 5, and 10 after CABG. Thromboxane formation, aggregation, and -granule secretion were effectively inhibited by 30 or 100 µmol/L aspirin in vitro before CABG, but this inhibition was prevented or attenuated after CABG. Whereas the inhibition of thromboxane formation and aggregation by aspirin in vitro partly recovered at day 10 after CABG, oral aspirin (100 mg/d) remained ineffective. The inducible isoform of cyclooxygenase in platelets, COX-2, has been suggested to confer aspirin resistance. In fact, immunoreactive COX-2 was increased 16-fold in platelets at day 5 after CABG, but the COX-2 selective inhibitor celecoxib did not alter aspirin-resistant thromboxane formation. By contrast, the combined inhibitor of thromboxane synthase and thromboxane receptor antagonist terbogrel equally prevented thromboxane formation of platelets obtained before (control) and after CABG.

Conclusions— Platelet aspirin resistance involves an impairment of both in vivo and in vitro inhibition of platelet functions and is probably due to a disturbed inhibition of platelet COX-1 by aspirin.

Key Words: aspirin • platelets • thromboxane • bypass surgery

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