Choe Michael J, Packer Clifford D
Case Western Reserve School of Medicine, Cleveland Heights, OH, USA
Case Western Reserve School of Medicine, Cleveland Heights, OH, USA Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
Ann Pharmacother. 2015 Jan;49(1):140-4. doi: 10.1177/1060028014555540. Epub 2014 Oct 16.
To report a case of severe rebound thrombocytopenia after temporary discontinuation of romiplostim during splenectomy in the context of refractory immune (idiopathic) thrombocytopenic purpura (ITP).
A 65-year-old man with a history of severe refractory ITP failing multiple treatments was considered for romiplostim therapy. He was initiated on 1 µg/kg and titrated upward to 4 µg/kg to elevate and stabilize his platelet levels prior to splenectomy. On day 74 of his clinical course, his platelets increased to 434 × 10(9)/L, and his scheduled dose of romiplostim was withheld on day 75 for fear of romiplostim-induced postsplenectomy rebound thrombocytosis. On day 78, his platelets dropped precipitously to 9 × 10(9)/L, and he experienced multiple episodes of epistaxis. He was reinitiated at 5 µg/kg and soon recovered. He later missed a scheduled dose of romiplostim, and his platelets fell to 23 × 10(9)/L. After resuming romiplostim at 8 µg/kg, his platelets continued to recover.
Romiplostim, a thrombopoietin mimetic is directly regulated by megakaryocytes and existing circulating platelets via a negative feedback mechanism. This explains the theoretical risk of rapid clearance of romiplostim caused by an increased platelet pool. Clinically, alternative causes of his severe postoperative thrombocytopenia were considered and deemed unlikely. The rebound effect was observed after romiplostim was withdrawn on 2 occasions, and platelet counts improved after restarting romiplostim. The Naranjo Adverse Drug Reaction Probability Score of 7 suggests a probable adverse drug reaction.
Physicians using romiplostim as a bridge to splenectomy should be cautious about withholding a scheduled dose around the time of surgery.
报告1例难治性免疫性（特发性）血小板减少性紫癜（ITP）患者在脾切除术中临时停用罗米司亭后发生严重血小板减少反弹的病例。
一名65岁男性，有严重难治性ITP病史，多种治疗均失败，考虑使用罗米司亭治疗。在脾切除术前，起始剂量为1μg/kg，并逐渐滴定至4μg/kg，以提高并稳定其血小板水平。在其临床病程的第74天，血小板升至434×10⁹/L，第75天因担心罗米司亭引起脾切除术后血小板增多反弹而停用了预定剂量的罗米司亭。第78天，其血小板急剧降至9×10⁹/L，且发生多次鼻出血。重新以5μg/kg的剂量用药后，他很快康复。后来他错过了一次预定的罗米司亭给药，血小板降至23×10⁹/L。以8μg/kg的剂量恢复使用罗米司亭后，其血小板继续回升。
罗米司亭是一种血小板生成素模拟物，通过负反馈机制直接受巨核细胞和循环中的现有血小板调节。这解释了血小板池增加导致罗米司亭快速清除的理论风险。临床上，考虑了其术后严重血小板减少的其他原因，认为可能性不大。两次停用罗米司亭后均观察到反弹效应，重新使用罗米司亭后血小板计数改善。Naranjo药物不良反应概率评分为7，提示可能为药物不良反应。
使用罗米司亭作为脾切除术桥梁的医生在手术前后应谨慎停用预定剂量的药物。
