Determinants of high on-treatment platelet reactivity and agreement between VerifyNow and Multiplate assays

Abstract

Dual antiplatelet therapy with clopidogrel is a regimen used before and after drug-eluting stent (DES) implantation. Point-of-care platelet reactivity assays are easy-to-use methods to determine adequate response to the drug. The aim of this study was a comparison of the two platelet reactivity assays: Multiplate and VerifyNow and an identification of factors potentially influencing the results of these tests, including common genetic polymorphisms. The study included 39 patients receiving 75 mg clopidogrel daily before angioplasty with DES implantation. Platelet reactivity was measured with Multiplate and P2Y VerifyNow assays. Genetic polymorphisms of CYP2C19*2, ABCB1 3435C > T, and CYP3A4*1G were determined with PCR-RFLP method and CYP2C19*17 was determined by means of an allele-specific PCR. Agreement between Multiplate and VerifyNow assays was poor (Cohen's κ = 0.056, p = .273). Hematocrit significantly negatively correlated with VerifyNow assayed platelet reactivity (r = -.487, p = .002). Female sex was significantly associated with higher VerifyNow assay results after adjustment to hematocrit (253.2 ± 47.6 PRU vs. 195.9 ± 56.9 PRU, p = .013) and the prevalence of high-on-treatment platelet reactivity (OR: 8.50; 95% CI 1.13-77.60, p = .024). Reactivity measured with Multiplate was lower in women (82.3 vs. 175.6 AU·min, p = .037) and in patients who received calcium channel blockers (74.7 vs. 191.7 AU·min, p = .002). None of the studied polymorphisms significantly influenced platelet aggregation measurements. In conclusion, different aspects modify between-patient variability of the Multiplate and VerifyNow assays and agreement between those two assays was poor.

Comparison of three common whole blood platelet function tests for in vitro P2Y12 induced platelet inhibition

“…This may be due to study design; additionally, it has previously been reported that VerifyNow ® may overestimate the therapeutic response to clopidogrel in some individuals, potentially due to the utilization of PGE1 in addition to ADP [32]. This is in line with the results of our study, where low interchangeability of VerifyNow ® results were seen with TEG ® 6s and Multiplate ® results, and is further confirmed by a previous study noting poor agreement between VerifyNow ® and Multiplate ® [33].…”

Effects of age, gender and menstrual cycle on platelet function assessed by impedance aggregometry

“…The lower Hct found in women of fertile age is likely due to regular blood loss through menstruations. However, the small differences in Hct found in our study are unlikely to have had any impact on aggregation since others have shown that Hct does not affect platelet aggregation when assessed by Multiplate [20,[26][27][28].…”