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Received on September 30, 2006
Accepted on January 19, 2007
Hemostasis and Thrombosis |
1 Department of Medicine III, University of Heidelberg, Germany
2 Institute of Pharmacology and Clinical Pharmacology, University of Duesseldorf, Germany
* To whom correspondence should be addressed. E-mail: Boris.Ivandic{at}med.uni-heidelberg.de.
Background: Insufficient platelet inhibition is associated with an increased cardiovascular risk in up to 30% of patients taking regular doses of aspirin. We describe an assay to study aspirin responsiveness.
Methods: We performed impedance aggregometry on diluted whole blood with 1 mg/L collagen and 0.5 mmol/L arachidonic acid (AA). We measured thromboxane B2 (TXB2) by RIA. We examined 66 healthy control individuals, 144 aspirin users with stable coronary artery disease (CAD), and 245 CAD patients treated with aspirin and clopidogrel. Nonresponsive samples were incubated with excess dl-lysinmonoacetylsalicylic acid.
Results: Assay imprecision (CV) was 9.8% and 8.2% at mean (SD) 6-min impedance of 13.7 (2.8) 
and 13.6 (2.3) for collagen and AA, respectively. Collagen induced stronger aggregation (P = 0.0199) in women [n = 28, 14.6 (2.4) ] than in men [n = 38, 13.1 (2.9) ], even after sample incubation with 0.1 mmol/L acetylsalicylic acid (ASA) or 1 µmol/L terbogrel, a combined inhibitor of thromboxane synthase and receptors. The sex association persisted in aspirin users, but not if clopidogrel was also taken. A 6-min impedance >8 with collagen (mean - 2 SD of the controls) was taken as evidence of nonresponsiveness, particularly if incubation with ASA did not inhibit aggregation further (>2 ). Compared with AA, collagen identified more nonresponsive samples among aspirin users (15%) and CAD patients who also received clopidogrel (10%). Incubation with ASA improved inhibition of aggregation in 70% of samples and consistently reduced TXB2 formation during aggregation.
Conclusions: Impedance aggregometry may prove useful to study aspirin responsiveness, and incubation with ASA may help to identify nonresponders and classify resistance.
The following articles in journals at HighWire Press have cited this article:
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