Platelet aggregation response in immune thrombocytopenia patients treated with romiplostim
Platelet aggregation response in immune thrombocytopenia patients treated with romiplostim
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DOI：
10.1007/s00277-018-3556-6
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发表时间：
2019-03-01
影响因子：
3.5
通讯作者：
Kuter, David J.
中科院分区：
文献类型：
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作者：
Al-Samkari, Hanny;Van Cott, Elizabeth M.;Kuter, David J.
血小板生成素受体激动剂罗米司亭用于长期治疗慢性免疫性血小板减少症（ITP）。 ITP 患者的血栓形成风险增加，如果 romiplostim 增加血小板高反应性或引起自发性血小板聚集，则血栓形成风险可能会加剧。为了研究这种可能性，本研究检查了 romiplostim 治疗的 ITP 患者和健康受试者的血小板功能。对每个受试者进行利用花生四烯酸、胶原蛋白、肾上腺素、瑞斯托菌素、ADP和盐水（以评估自发聚集）的光透射血小板聚集测量。此外，还确定了每位患者的 ADP AC(50)（诱导半最大聚集的 ADP 浓度），作为血小板反应性改变的灵敏测量。 15 名 ITP 患者和 7 名健康受试者参加了该研究。所有 ITP 患者均患有活动性疾病，并且每周接受 romiplostim 作为唯一针对 ITP 的治疗。 ITP 患者和健康受试者对强激动剂花生四烯酸、胶原蛋白和瑞斯托菌素的血小板聚集反应没有显着差异（分别为 P=0.2442、P=0.0548 和 P=0.0879）。与健康受试者相比，ITP 患者对弱激动剂的血小板聚集显着降低：ADP 聚集中位数（范围）为 45% (15-84%) 与 89% (70-95%) (P=0.0010)，肾上腺素聚集为 21% (1.6-90%) 与 88% (79-94%) (P=0.0085)。 ITP 患者的 ADP 中位 AC(50) 是健康受试者的三倍（6.3M vs 2.1M）（P=0.0049）。在任何患者中均未观察到明显的自发聚集。接受 romiplostim 治疗的 ITP 患者的血小板没有显示出自发聚集或高反应性的证据，而是对 ADP 和肾上腺素的聚集反应适度降低。
The thrombopoietin receptor agonist romiplostim is used for the long-term treatment of chronic immune thrombocytopenia (ITP). ITP patients have an increased thrombotic risk, which could be exacerbated if romiplostim increased platelet hyperreactivity or caused spontaneous platelet aggregation. To investigate this possibility, this study examined platelet function in romiplostim-treated ITP patients and healthy subjects. Light transmission platelet aggregometry utilizing arachidonic acid, collagen, epinephrine, ristocetin, ADP, and saline (to assess spontaneous aggregation) was performed for each subject. In addition, the ADP AC(50) (ADP concentration that induced half-maximal aggregation) was determined for each patient as a sensitive measurement of altered platelet reactivity. Fifteen ITP patients and 7 healthy subjects entered the study. All ITP patients had active disease and were receiving weekly romiplostim as the sole ITP-directed therapy. Platelet aggregation in response to the strong agonists arachidonic acid, collagen, and ristocetin was not significantly different between ITP patients and healthy subjects (P=0.2442, P=0.0548, and P=0.0879, respectively). Platelet aggregation in response to weak agonists was significantly reduced in ITP patients compared with that in healthy subjects: median (range) aggregation to ADP, 45% (15-84%) versus 89% (70-95%) (P=0.0010), and epinephrine, 21% (1.6-90%) versus 88% (79-94%) (P=0.0085). The median AC(50) of ADP was threefold higher in ITP patients versus that in healthy subjects (6.3M vs 2.1M) (P=0.0049). Significant spontaneous aggregation was not observed in any patient. Platelets from romiplostim-treated ITP patients do not show evidence for spontaneous aggregation or hyperreactivity, but instead have a modestly reduced aggregation response to ADP and epinephrine.