Determination of aspirin responsiveness by use of whole blood platelet aggregometry

Back round: 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 B-2 (TXB2) by RIA. We examined 66 healthy control individuals, 144 aspirin users with stable coronary artery disease (CAD), and 245 CAD patients treated with aspirins 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) Omega and 13.6 (2.3) 0 for collagen and AA, respectively. Collagen induced stronger aggregation (P = 0.0199) in women [n = 28,14.6 (2.4) Omega] than in men [n = 38, 13.1 (2.9) Omega], even after sample incubation With 0.1 mmol/L acetylsalicylic acid (ASA) or 1 mu mol/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 Omega with collagen (mean - 2 SD of the controls), was taken as evidence of nonresponsiveness, particularly if incubation with ASA did hot inhibit aggregation further (> 2 Omega). 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. (c) 2007 American Association for Clinical Chemistry.