Identification of High Platelet Reactivity Despite ADP P2Y12 Inhibitor Treatment: Two Populations in the Vasodilator-Stimulated Phosphoprotein Assay and Variable PFA-P2Y Shapes of Curve

Abstract

Abstract Introduction Response to ADP P2Y12 receptor inhibition by clopidogrel can be evaluated by various techniques. Here, we compared a functional rapid point-of-care technique (PFA-P2Y) with the degree of biochemical inhibition assessed by the VASP/P2Y12 assay. Methods Platelet response to clopidogrel was investigated in 173 patients undergoing elective intracerebral stenting (derivation cohort n = 117; validation cohort n = 56). High platelet reactivity (HPR) was defined as PFA-P2Y occlusion time 50%. Results In the derivation cohort, receiver operator characteristics analysis for the ability of PFA-P2Y to detect biochemical HPR showed high specificity (98.4%) but poor sensitivity (20.0%) and a very low area under the curve (0.59). The VASP/P2Y12 assay revealed two coexisting platelet populations with different levels of vasodilator-stimulated phosphoprotein (VASP) phosphorylation: a fraction of highly phosphorylated, inhibited platelets and another of poorly phosphorylated, reactive platelets. Analysis of the PFA-P2Y curve shape revealed different types, categorized by time of occlusion (300 seconds), and pattern (regular, irregular, and atypical). Noteworthy, curves with late occlusion and permeable curves with an irregular or atypical pattern correlated with VASP-PRI >50% and smaller sizes of the inhibited platelet subpopulation. Considering the PFA-P2Y shape of the curve for the detection of HPR improved sensitivity (72.7%) and preserved specificity (91.9%), with a rather high AUC (0.823). The validation cohort confirmed the VASP/P2Y12 assay data and the usefulness of considering the PFA-P2Y curve shape. Conclusion In patients treated with acetylsalicylic acid and clopidogrel for 7-10 days, the VASP/P2Y12 assay reveals two coexisting subpopulations of differentially inhibited platelets, whose relative sizes predict global PRI and distinct PFA-P2Y curve patterns, indicating incomplete clopidogrel efficacy. The detailed analysis of both VASP/P2Y12 and PFA-P2Y is necessary for optimal detection of HPR.

Keywords

• adp p2y12 receptor
• clopidogrel
• response
• laboratory data
• vasp