A comparison of platelet function tests and thromboxane metabolites to evaluate aspirin response in healthy individuals and patients with coronary artery disease

Abstract

Individualised antiplatelet therapy and platelet function testing have attracted considerable clinical interest, but several aspects of test performance have not been thoroughly evaluated. We investigated repeatability and concordance of light transmission aggregometry (LTA) induced with arachidonic acid (AA) 1.0 mM, PFA-100 induced with collagen/epinephrine, multiple electrode aggregometry (MEA) induced with AA 0.5 or 0.75 mM and VerifyNow Aspirin. Patients with stable coronary artery disease (n=43) and healthy individuals (n=21) were included. All tests were performed in duplicate at baseline in healthy individuals and in duplicate for four days in all study participants during aspirin treatment. Serum and urinary thromboxane metabolites were measured several times to evaluate cyclooxygenase-1 inhibition by aspirin. MEA was most sensitive for aspirin as treatment induced a 12-fold difference in AA-induced platelet aggregation. Coefficients of variation for duplicate measurements at baseline (0.4-12%), during aspirin treatment (3-46%) and for day-to-day variability (3-37%) differed markedly between tests and were lowest for VerifyNow. The prevalence of aspirin low-responsiveness also differed between tests (0-9%) and the agreement was low: kappa<or=0.21 for all tests compared with AA-induced LTA (reference test), which correlated best with VerifyNow (r=0.43, p<0.001). Urinary thromboxane metabolites did not correlate with any platelet function test, whereas serum thromboxane correlated with VerifyNow Aspirin (r=0.41, p=0.001). Overall, repeatability was moderate and the correlation between tests was low. VerifyNow Aspirin proved most reproducible, and this was the only assay showing a significant positive correlation with serum thromboxane. This study demonstrated that conclusions based on platelet function testing strongly depend on the assay used.

Differences in Whole Blood Platelet Aggregation at Baseline and in Response to Aspirin and Aspirin Plus Clopidogrel in Patients With Versus Without Chronic Kidney Disease

“…In addition, platelet function assays may have suboptimal reproducibility. 27 As such, previously reported variability in antiplatelet effects of clopidogrel is partly explained by CYP2C19 polymorphisms. 28,29 Therefore, we measured CYP2C19 polymorphisms that may affect clopigogrel-induced platelet inhibition.…”

The prognostic utility of tests of platelet function for the detection of ‘aspirin resistance’ in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation

“…In parallel, a number of different studies have shown platelet function assay results to lack correlation and agreement among themselves, thus identifying different patients as poor responders to aspirin and having different determinants of response. 37,75,76 Which platelet function assay, if any, is the most clinically predictive of future major adverse cardiovascular events remains to be established. 77 As a consequence, the natural history of aspirin resistance remains somewhat uncertain.…”

Platelet aggregation pathway

“…The term aspirin resistance has also been used in the laboratory context. Here, aspirin resistance describes persistent platelet reactivity in vitro , despite the use of aspirin, measured by various platelet function tests such as measurement of serum and urinary thromboxane metabolites, and AA-induced platelet aggregation, collagen-induced platelet aggregation, or ADP-induced platelet aggregation [35,36]. One limitation of the assessment of the various functional indexes of platelet capacity that can be measured ex vivo with in-vitro tests is the largely unknown translational relevance to the actual occurrence of platelet activation and inhibition in vivo [37].…”