title: Relation between ticagrelor response and levels of circulating reticulated platelets in patients with non-ST elevation acute coronary syndromes.
abstract: Antiplatelet responses to clopidogrel and prasugrel are highly variable and subject to significant rates of high on-treatment platelet reactivity (HTPR) after percutaneous coronary intervention (PCI). The proportion of circulating young reticulated platelets (RPs) inversely correlates with responsiveness to both agents. We aimed to determine the relationship between RPs and on-treatment platelet reactivity in ticagrelor-treated patients. Patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) treated with PCI and ticagrelor were tested for platelet reactivity using the VerifyNow P2Y12 assay and multiplate aggregometry. RPs levels were determined using flow cytometry with thiazole orange staining. Tests were performed at 2-4 and 30 days post-PCI. Fifty three patients were included (mean age 62.6 ± 9.8 years, 18.9 % women, 35.8 % diabetes), of which 41 patients (77 %) completed follow-up. Variability in response to ticagrelor was very low according to both assays with no identified cases of HTPR at either time-point. In addition, there were no differences in platelet reactivity, as analyzed by the VerifyNow P2Y12 assay, or in the proportion of RPs between the two time points (p > 0.5). With the multiplate assay, platelet reactivity increased between the two time-points (8.6 ± 6.0 vs. 15.5 ± 11 AU*min; p = 0.0007). There was no significant correlation between RPs and platelet reactivity at both time-points and using both assays (p > 0.5). There were no cases of HTPR up to 30-days post-PCI in patients with NSTE-ACS treated with ticagrelor. In this cohort, no correlation between % RPs and platelet reactivity was observed. Attenuation of RP-induced platelet reactivity as a novel mechanism for ticagrelor's benefit requires further investigation.
authors: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, GRB 740, Boston, MA, 02114, USA, muthu@md.northwestern.edu.
authors: Muthiah
authors: M
authors: Vaduganathan
authors: Noa
authors: N
authors: Zemer-Wassercug
authors: Eldad
authors: E
authors: Rechavia
authors: Hila
authors: H
authors: Lerman-Shivek
authors: Leor
authors: L
authors: Perl
authors: Dorit
authors: D
authors: Leshem-Lev
authors: Katia
authors: K
authors: Orvin
authors: Ran
authors: R
authors: Kornowski
authors: Eli I
authors: EI
authors: Lev
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage*; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*; D000077486:Ticagrelor; D013997:Time Factors
chemical_list: C548576:P2RY12 protein, human; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077486:Ticagrelor; D000241:Adenosine
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