Division of Hematology, Massachusetts General Hospital, Zero Emerson Place, Harvard Medical School, Suite 118, Boston, MA, 02114, USA.
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Ann Hematol. 2019 Mar;98(3):581-588. doi: 10.1007/s00277-018-3556-6. Epub 2018 Nov 17.
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 (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 of ADP was threefold higher in ITP patients versus that in healthy subjects (6.3 μM vs 2.1 μM) (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.
血小板生成素受体激动剂罗米司亭被用于慢性免疫性血小板减少症（ITP）的长期治疗。ITP 患者存在血栓形成风险增加，如果罗米司亭增加血小板高反应性或导致自发性血小板聚集，则可能会使这种风险加剧。为了研究这种可能性，本研究检查了罗米司亭治疗的 ITP 患者和健康受试者的血小板功能。对每位受试者进行了使用花生四烯酸、胶原、肾上腺素、瑞斯托霉素、ADP 和盐水（评估自发性聚集）的透光比浊血小板聚集测定。此外，还为每位患者确定了 ADP AC（诱导血小板聚集达到半最大时的 ADP 浓度），作为血小板反应性改变的敏感测量指标。15 名 ITP 患者和 7 名健康受试者入组该研究。所有 ITP 患者均患有活动性疾病，且每周接受罗米司亭治疗，作为唯一的 ITP 靶向治疗。与健康受试者相比，ITP 患者对强激动剂花生四烯酸、胶原和瑞斯托霉素的血小板聚集反应没有显著差异（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反应明显降低：ADP 的中位（范围）聚集率为 45%（15-84%）比 89%（70-95%）（P=0.0010），肾上腺素的中位（范围）聚集率为 21%（1.6-90%）比 88%（79-94%）（P=0.0085）。与健康受试者相比，ITP 患者的 ADP AC 中位数高 3 倍（6.3 μM 比 2.1 μM）（P=0.0049）。未在任何患者中观察到明显的自发性聚集。罗米司亭治疗的 ITP 患者的血小板没有自发性聚集或高反应性的证据，但对 ADP 和肾上腺素的聚集反应适度降低。
