title: Comparison of conventional aggregometry with VASP for monitoring P2Y12-specific platelet inhibition.
abstract: No consensus exists regarding the optimal estimate of light transmission aggregometry (LTA) to reflect P2Y12 ADP receptor inhibition in patients receiving thienopyridine therapy. Currently, the only completely P2Y12-receptor specific method is the measurement of vasodilator stimulated phosphoprotein (VASP) phosphorylation (PRI) with flow cytometry. In the current analysis, we aimed to test the superiority of the late platelet aggregation value over other estimates of light transmission aggregometry in determining P2Y12-receptor inhibition by comparing them to VASP-PRI. On-clopidogrel platelet reactivity was measured in 121 clopidogrel-naïve patients who underwent elective coronary stent implantation. Samples for LTA and VASP assessments were drawn at 12-18 hours after a 600-mg loading dose of clopidogrel and 25 days after the intervention. ADP 5 µM-induced maximal aggregation (AGGmax), 6-minute late aggregation (AGGlate), 6-minute disaggregation (disAGG) and area under the aggregation curve (AUC) were compared to VASP-PRI. Categorical agreement with VASP-defined normal and high platelet reactivity (HPR: PRI ≥ 50%) was calculated according to the optimal cutoff values obtained with receiver-operating characteristic (ROC) curves. The evaluation of 242 measurements showed significant, moderate-strength correlations between VASP-PRI and LTA estimates without the superiority of AGGlate over other estimates (AGGmax: ρ = 0.47; AGGlate: ρ = 0.45; disAGG: ρ = -0.44; AUC: ρ = 0.50). Notably, there were considerable intra-individual differences between VASP and LTA testing. LTA estimates were similar in classifying patients to VASP-defined normal or HPR categories (AGGmax: κ = 0.41; AGGlate: κ = 0.45; disAGG: κ = 0.44; AUC: κ = 0.44). When all estimates of LTA were compared in multivariable models, AUC proved to be the independent linear determinant of VASP-PRI and the best predictor of HPR. Estimates of LTA seem equal in determining the degree of P2Y12-receptor inhibition or in predicting VASP-defined HPR without the superiority of AGGlate over others. These results reject a commonly used hypothesis and might contribute to the standardization of the LTA assay.
authors.affiliation: Department of Interventional Cardiology, Heart Institute, University of Pécs, Hungary. daniel.aradi@kk.pte.hu
authors.forename: Dániel
authors.initials: D
authors.lastname: Aradi
authors.forename: Tamás
authors.initials: T
authors.lastname: Magyarlaki
authors.forename: Margit
authors.initials: M
authors.lastname: Tokés-Füzesi
authors.forename: Orsolya
authors.initials: O
authors.lastname: Rideg
authors.forename: András
authors.initials: A
authors.lastname: Vorobcsuk
authors.forename: András
authors.initials: A
authors.lastname: Komócsi
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000787:Angina Pectoris / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood*; D000077144:Clopidogrel; D005434:Flow Cytometry; D006801:Humans; D008840:Microfilament Proteins / Q000097:blood*; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests / Q000379:methods*; D011446:Prospective Studies; D058925:Receptors, Purinergic P2Y12 / Q000097:blood*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine