Bonhomme Fanny, Bonvini Robert, Reny Jean-Luc, Poncet Antoine, Fontana Pierre
Division of Anesthesiology, Geneva University Hospitals , Geneva , Switzerland .
Platelets. 2015;26(4):324-30. doi: 10.3109/09537104.2015.1035247. Epub 2015 Apr 23.
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.
对接受P2Y12抑制剂治疗的患者进行出血管理具有挑战性。关于普拉格雷或替格瑞洛治疗患者的血小板输注疗效，可用数据很少。本研究的目的是评估在接受阿司匹林和急性冠状动脉综合征负荷剂量普拉格雷或替格瑞洛治疗的患者富血小板血浆（PRP）中，恢复血小板反应性所需的最小血小板补充量（以未受抑制血小板与受抑制血小板的比例表示）。将患者的PRP样本与来自健康志愿者的混合PRP按比例增加进行体外混合。使用光透射聚集法用二磷酸腺苷（ADP）、花生四烯酸、胶原或凝血酶受体激活肽激发血小板反应性。主要终点是恢复ADP诱导的最大聚集（ADP-Aggmax）值高于40%的患者样本比例。在接受普拉格雷治疗的患者（n = 32）中，随着混合PRP补充量的增加，ADP-Aggmax逐渐增加，每增加20%未受抑制血小板与受抑制血小板的比例，平均增加7.9%（95%CI[7.1；8.8]，p < 0.001）。60%的比例与90%的患者达到主要终点相关。在接受替格瑞洛治疗的患者（n = 15）中，任何水平的补充量均未使ADP-Aggmax显著增加。总之，体外添加未受抑制的血小板可显著改善接受普拉格雷治疗患者的ADP-Aggmax，且具有剂量依赖性效应。在接受替格瑞洛治疗的患者中没有这种逆转的证据。这些结果表明，与接受替格瑞洛治疗的患者相比血小板输注在减轻接受普拉格雷治疗患者的出血方面可能更有效。
