Head‐to‐Head comparison of consensus‐recommended platelet function tests to assess P2Y12 Inhibition : insights for multi‐center trials
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Journal of clinical medicine ; vol. 9, no. 2.Publisher(s)
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Abstract(s)
The vasodilator‐associated stimulated phosphoprotein (VASP) phosphorylation level is a
highly specific method to assess P2Y12 receptor inhibition. Traditionally, VASP phosphorylation is
analyzed by flow cytometry, which is laborious and restricted to specialized laboratories. Recently,
a simple ELISA kit has been commercialized. The primary objective of this study was to compare
the performance of VASP assessment by ELISA and flow cytometry in relation to functional platelet
aggregation testing by Multiplate® whole‐blood aggregometry. Blood from 24 healthy volunteers
was incubated with increasing concentration of a P2Y12 receptor inhibitor (AR‐C 66096). Platelet
function testing was carried out simultaneously by Multiplate® aggregometry and by VASP
assessment through ELISA and flow cytometry. As expected, increasing concentrations of the P2Y12
receptor inhibitor induced a proportional inhibition of platelet aggregation and P2Y12 receptor
activation across the modalities. Platelet reactivity index values of both ELISA‐ and flow cytometry‐
based VASP assessment methods correlated strongly (r = 0.87, p < 0.0001) and showed minimal bias
(1.05%). Correlation with Multiplate® was slightly higher for the flow cytometry‐based VASP assay
(r = 0.79, p < 0.0001) than for the ELISA‐based assay (r = 0.69, p < 0.0001). Intraclass correlation (ICC)
was moderate for all the assays tested (ICC between 0.62 and 0.84). However, categorization into
low, optimal, or high platelet reactivity based on these assays was strongly concordant (κ between
0.86 and 0.92). In conclusion, the consensus‐recommended assays with their standardized cut‐offs
should not be used interchangeably in multi‐center clinical studies but, rather, they should be
standardized throughout sites.