Weber E, Moulis G, Mahévas M, Guy C, Lioger B, Durieu I, Hunault M, Ramanantsoa M, Royer B, Default A, Pérault-Pochat M-C, Moachon L, Bernard N, Bardy G, Jonville-Bera A-P, Geniaux H, Godeau B, Cathébras P
Service de médecine interne, CHU de Saint-Étienne, hôpital Nord, 42055 Saint-Étienne cedex 2, France.
Service de médecine interne, CHU de Toulouse, France; UMR 1027 Inserm, université de Toulouse, France; CIC 1436, axe pharmaco-épidémiologie, CHU de Toulouse, France.
Rev Med Interne. 2017 Mar;38(3):167-175. doi: 10.1016/j.revmed.2016.09.016. Epub 2016 Oct 25.
Thrombopoietin-receptor agonists (TPO-RA) are marketed for immune thrombocytopenia (ITP). They have been associated to thrombosis occurrence in randomized controlled trials. However, the characteristics of these thromboses in the real-life practice as well as their management are poorly known. The objectives of this study were to determine the risk factors, circumstances and management of thrombosis occurring during exposure to TPO-RA in ITP.
We carried out a multicentre retrospective study in France. Moreover, all cases reported to the French pharmacovigilance system were also analyzed.
Overall, 41 thrombosis (13 arterial) in 36 ITP patients (14 males and 22 females, mean age: 59 years) were recorded between January 2009 and October 2015. Twenty patients were treated with romiplostim, 15 with eltrombopag and 1 was treated by both medications. Thirty-three (92%) of the patients had another risk factor for thrombosis. Ten (28%) had an history of thrombosis and 13 (36%) received immunoglobulin in the month preceding the thrombotic event. Three had antiphospholipid antibodies; congenital low-risk thrombophilia was found in 4 cases; 18 patients (50%) were splenectomized. Median platelet count at the time of thrombosis was 172G/l (1-1049G/l). In 22 patients (56%), a good prognosis was associated with the thrombosis and was not linked with TPO-RA withdrawal. Bleeding events occurred in 14% of the patients treated with antiplatelet or anticoagulant drug, including 5% serious events (1 death of intracranial haemorrhage, 1 death of haemorrhagic shock).
The thrombotic risk may be carefully assessed before starting TPO-RA in ITP patients. The impact of antiphospholipid antibodies and of congenital thrombophilia remains to be defined. Thrombosis evolution seems independent of TPO-RA management. Bleeding manifestations seem rare. Poor prognosis was mainly due to ischemic sequelae.
血小板生成素受体激动剂（TPO-RA）已被用于治疗免疫性血小板减少症（ITP）。在随机对照试验中，它们与血栓形成有关。然而，在实际临床实践中这些血栓的特征及其处理方法却鲜为人知。本研究的目的是确定ITP患者在使用TPO-RA期间发生血栓形成的危险因素、情况及处理方法。
我们在法国开展了一项多中心回顾性研究。此外，还对向法国药物警戒系统报告的所有病例进行了分析。
总体而言，在2009年1月至2015年10月期间，共记录了36例ITP患者（14例男性和22例女性，平均年龄59岁）发生的41次血栓形成事件（13次动脉血栓）。20例患者接受了罗米司亭治疗，15例接受艾曲泊帕治疗，1例同时接受了这两种药物治疗。33例（92%）患者存在其他血栓形成危险因素。10例（28%）有血栓形成病史，13例（36%）在血栓形成事件前一个月接受了免疫球蛋白治疗。3例有抗磷脂抗体；4例发现先天性低风险血栓形成倾向；18例（50%）患者接受了脾切除术。血栓形成时的血小板计数中位数为172G/l（1-1049G/l）。22例（56%）患者的血栓形成预后良好，且与停用TPO-RA无关。接受抗血小板或抗凝药物治疗的患者中有14%发生了出血事件，其中5%为严重事件（1例颅内出血死亡，1例出血性休克死亡）。
在ITP患者开始使用TPO-RA之前，可能需要仔细评估血栓形成风险。抗磷脂抗体和先天性血栓形成倾向的影响仍有待确定。血栓形成的演变似乎与TPO-RA的管理无关。出血表现似乎很少见。预后不良主要是由于缺血性后遗症。
