Key result
Arachidonic acid assays show high discriminative power for detecting low-dose aspirin antiplatelet effects.
Why the study?
Do routine laboratory methods accurately detect the antiplatelet effect of aspirin compared to reference methods in healthy volunteers?
Do routine laboratory methods accurately detect the antiplatelet effect of aspirin compared to reference methods in healthy volunteers?
Only laboratory assays that use arachidonic acid as an agonist or directly measure COX-1 acetylation are reliable for assessing the antiplatelet effect of aspirin.
COX-1-specific assays may reliably confirm aspirin effect where routine tests fail; leaves open clinical utility in patients.
BACKGROUND: Aspirin, a commonly used antiplatelet agent, blocks platelet thromboxane A₂ (TXA₂) formation from arachidonic acid (AA) by acetylating platelet cyclooxygenase-1 (COX-1). Laboratory methods currently used to detect this antiplatelet effect of aspirin provide variable results. We have reported three methods that assess platelet COX-1 acetylation (inactivation) by aspirin and its direct consequences. The first and second assays use monoclonal anti-human-COX-1 antibodies that only detect acetylated (inactivated) COX-1 and active (non-acetylated) COX-1, respectively. The third method measures platelet production of TXB₂ (the stable metabolite of TXA₂) in vitro in response to AA. We compared the results of these three reference methods with other routinely used methods for assessing the functional consequences aspirin treatment. METHODS: 108 healthy volunteers were treated with low-dose aspirin for 7 days. On day 7 following aspirin treatment COX-1 in the platelets was fully acetylated whereas only non-acetylated COX-1 was present in the day 0 platelets. Further, TXB2 production by day 7 platelets was completely blocked. The following tests were performed on the samples obtained from study participants before and after seven days of aspirin treatment: PFA-100 closure time with collagen/epinephrine cartridge, VerifyNow (VN) Aspirin Assay, platelet aggregation and ATP secretion using AA, ADP, epinephrine and collagen as agonists. RESULTS: Comparing the pre-treatment and day 7 values, methods that use AA as platelet agonist (AA-induced platelet aggregation/secretion and VN Aspirin Assay) showed high discriminative power. In contrast, results of the other tests showed considerable overlap between day 7 and day 0 values. CONCLUSIONS: Only assays that clearly distinguish between acetylated and non-acetylated platelet COX-1 are useful for establishing the antiplatelet effect of aspirin. The other tests are not suitable for this purpose.
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Kovács et al. (2013) studied healthy volunteers (n=108). low-dose aspirin vs. pre-treatment (day 0) was evaluated on discriminative power of laboratory methods to detect aspirin effect (pre-treatment vs day 7). In 108 healthy volunteers, assays using arachidonic acid as a platelet agonist showed high discriminative power for detecting the antiplatelet effect of 7-day low-dose aspirin treatment.
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