March 1, 2007Open Access
View Full PaperDetermination of Aspirin Responsiveness by Use of Whole Blood Platelet Aggregometry
Key Result
Impedance aggregometry with collagen identified aspirin nonresponsiveness in 15% of aspirin users and 10% of CAD patients on aspirin and clopidogrel.
Study Design
Type
Observational (n=455)
Structured PICO
Can impedance aggregometry with collagen and arachidonic acid accurately determine aspirin responsiveness in healthy individuals and CAD patients?
P
Population
455 participants comprising 66 healthy controls, 144 aspirin users with stable CAD, and 245 CAD patients treated with aspirin and clopidogrel.
E
Exposure
Impedance aggregometry on diluted whole blood with 1 mg/L collagen and 0.5 mmol/L arachidonic acid (AA)
O
Outcome
Aspirin responsiveness (platelet aggregation measured by impedance aggregometry and thromboxane B2 formation)surrogate
Impedance aggregometry using collagen and arachidonic acid may be a useful assay to identify aspirin nonresponders and classify resistance in CAD patients.
Abstract
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 B(2) (TXB(2)) 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) Omega and 13.6 (2.3) Omega 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 micromol/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 not 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 TXB(2) 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.