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-Agg_max) value above 40%. In patients treated with prasugrel (n = 32), ADP-Agg_max 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-Agg_max did not significantly increase with any level of supplements. In conclusions, ex vivo addition of non-inhibited platelets significantly improved ADP-Agg_max 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.

• Platelet function tests
• platelet transfusion
• prasugrel
• ticagrelor

Acknowledgements

We thank Severine Nolli and Nicolas Lorenzon for their excellent technical assistance and Youssef Daali for helpful discussions.

Declaration of interest

This study was supported by the department of Anesthesiology, Pharmacology and Intensive Care, Geneva University Hospitals, Geneva, Switzerland. Pierre Fontana is supported by the Swiss National Science Foundation (grant No 320030_144150). Pierre Fontana and Fanny Bonhomme received an unrestricted grant from Astra Zeneca.