title: Impact of non-inhibited platelet supplementation on platelet reactivity in patients treated with prasugrel or ticagrelor for an acute coronary syndrome: An ex vivo study.
abstract: Managing bleeding in patients receiving P2Y12 inhibitors is challenging. Few data are available regarding the efficacy of platelet transfusion in patients treated with prasugrel or ticagrelor. The aim of this study was to evaluate the minimal amount of platelet supplementation (in terms of ratio of non-inhibited platelets to inhibited platelets) necessary to restore platelet reactivity in platelet-rich plasma (PRP) of patients treated with aspirin and a prasugrel or ticagrelor loading dose for an acute coronary syndrome. PRP samples from patients were mixed ex vivo with increasing proportions of pooled PRP from healthy volunteers. Platelet reactivity was challenged with adenosine diphosphate (ADP), arachidonic acid, collagen or thrombin receptor activating peptide using light transmission aggregometry. The primary endpoint was the proportion of patient samples recovering an ADP-induced maximal aggregation (ADP-Aggmax) value above 40%. In patients treated with prasugrel (n = 32), ADP-Aggmax increased progressively with supplements of pooled PRP, with an average increase of 7.9% (95% CI [7.1; 8.8], p < 0.001) per each 20% increase in the ratio of non-inhibited platelets to inhibited platelets. A ratio of 60% was associated with 90% of patients reaching the primary endpoint. In patients treated with ticagrelor (n = 15), ADP-Aggmax did not significantly increase with any level of supplements. In conclusions, ex vivo addition of non-inhibited platelets significantly improved ADP-Aggmax in patients treated with prasugrel with a dose-dependent effect. There was no evidence of such a reversal in patients treated with ticagrelor. These results suggest that platelet transfusion may be more effective in blunting bleeding in patients treated with prasugrel, than those treated with ticagrelor.
authors.affiliation: Division of Anesthesiology, Geneva University Hospitals , Geneva , Switzerland .
authors.forename: Fanny
authors.initials: F
authors.lastname: Bonhomme
authors.forename: Robert
authors.initials: R
authors.lastname: Bonvini
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Reny
authors.forename: Antoine
authors.initials: A
authors.lastname: Poncet
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontana
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000097:blood; D017713:Platelet Transfusion / Q000379:methods*; D000068799:Prasugrel Hydrochloride / Q000009:adverse effects / Q000097:blood*; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects* / Q000097:blood; D000077486:Ticagrelor
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine
keywords: Platelet function tests; platelet transfusion; prasugrel; ticagrelor