Platelet Cyclooxygenase Inhibition by Low-Dose Aspirin Is Not Reflected Consistently by Platelet Function Assays

Abstract

Platelet cyclooxygenase activity, as reflected by serum TXB(2) levels, is uniformly and persistently suppressed by low-dose aspirin in healthy subjects. However, the effect of aspirin is variably detected by functional assays, potentially leading to misclassification of "responder" as "resistant" phenotypes owing to poor reproducibility of functional measurements. The nonlinearity of the relationship between inhibition of TX production and inhibition of platelet function has important clinical implications.

How I use laboratory monitoring of antiplatelet therapy

“…Although a number of small studies have suggested possible benefit from guided therapy in these clinical settings and in children, it is prudent to consider that highly favorable results were reported from early small randomized controlled trials 73 in patients with coronary artery disease before much larger, more definitive randomized controlled trials failed to confirm any benefit from this approach. [74][75][76] There is a possible role for platelet function testing (1) to document patient adherence to antiplatelet therapy or to confirm suspected nonadherence in patients with ischemic events 42,49 and (2) to determine the timing of cardiac surgery following withdrawal of a P2Y 12 inhibitor …”

“…39 However, if "resistance" is defined in pharmacological terms as the failure of aspirin intake to fully inactivate its target, platelet COX-1, as evidenced by lack of inhibition of thromboxane B 2 generation, then aspirin resistance is either a very rare phenomenon [40][41][42] or does not exist. 17 Based on this pharmacologic definition, a study of 400 healthy volunteers failed to identify a single case of aspirin resistance.…”

“…17,42 Increasing the dose of aspirin will not improve platelet inhibition if the patient is not taking aspirin or is on a concomitant NSAID medication. 17 However, improving the patient's motivation, stopping NSAID therapy, or switching to an NSAID that does not interfere with the antiplatelet action of aspirin (eg, celecoxib, diclofenac) 45,50 will likely increase the extent and duration of platelet inhibition by a standard low-dose aspirin regimen.…”

“…In any event, the relationship is weaker than that between high platelet reactivity and thrombotic events, 78 and there is no convincing evidence that changing clopidogrel therapy based on platelet function monitoring can result in a reduction in bleeding events and some evidence that it may increase bleeding events. 79 However, we perform platelet function testing to (a) confirm suspected nonadherence in patients taking clopidogrel (or other antiplatelet therapy) or to confirm suspected nonadherence in patients with ischemic events 42,49 and (2) to determine the timing of cardiac surgery following withdrawal of a P2Y 12 inhibitor to provide reassurance to the surgeon and allow earlier operation in patients with urgent indications but in whom the surgeon may otherwise feel For personal use only. on May 10, 2018. by guest www.bloodjournal.org From obligated to wait the requisite number of days listed in the drug labeling or guidelines.…”

Platelet testing in flow diversion: a review of the evidence

“…Reported rates of aspirin resistance have varied widely in PFT assays, but studies that have specifically measured levels of COX-1 acetylation or thromboxane B 2 in the blood have failed to detect significant rates of aspirin resistance in healthy individuals when compliance is ensured. 9,21,31,41,42 In studies on clopidogrel, resistance is most commonly defined as high on-treatment platelet reactivity to ADP by the P2Y12 receptor, indicating limited platelet inhibition. Given the variability of the PFT assays employed and their respective cut-off values for defining high on-treatment platelet reactivity, reported rates of clopidogrel resistance have varied from as low as 16% to as high as 50%.…”