Department of Internal Medicine, Marmara University, Istanbul, Turkey.
Department of Hematology/Oncology, Sarah Bush Lincoln Hospital-Regional Cancer Center, Mattoon, IL, USA.
J Oncol Pharm Pract. 2021 Jan;27(1):253-257. doi: 10.1177/1078155220935490. Epub 2020 Jul 1.
Immune thrombocytopenia is an autoimmune disorder associated with increased thrombocyte destruction and impaired production in the bone marrow. Proposed mechanisms include an antibody or autoreactive T-cell-associated autoimmunity and thrombopoietin deficiency among others. Clinical manifestations are predominantly mucocutaneous hemorrhages including petechiae, purpura, mucosal bleeding in the urinary or the gastrointestinal tracts, menorrhagia, and epistaxis. The purpose of the treatment is to prevent bleeding rather than normalizing the platelet counts. First-line treatments include corticosteroids ± intravenous immunoglobulin and Anti-D which mainly decrease antibody-mediated platelet destruction and increase the number of peripheral Tregs. Second-line and subsequent therapies include splenectomy, chimeric anti-CD20 antibody (rituximab), which eliminates B cells and act as an immunomodulatory agent, and Thrombopoietin receptor agonists (romiplostim), which promote platelet production.
We describe a 40-year-old male patient diagnosed with immune thrombocytopenia that was refractory to first-line corticosteroid and intravenous immunoglobulin and second-line romiplostim monotherapy treatments. The patient was given the romiplostim and rituximab combination which not only successfully treated thrombocytopenia but also resulted in grade 3 bone pains and the patient's subsequent refusal to continue therapy.
Common adverse effects of rituximab are infusion reactions and prolonged immunosuppression; those of romiplostim include thrombosis, headaches, arthralgia-myalgia, and gastrointestinal symptoms. This case shows that romiplostim has not caused any discernible side effects when given alone, while combination with rituximab resulted in severe bone and joint pains. We hypothesize that this combination regimen shows a synergistic effect both in terms of efficacy and adverse-effect probability and/or severity.
免疫性血小板减少症是一种与骨髓中血小板破坏增加和产生受损有关的自身免疫性疾病。提出的机制包括抗体或自身反应性 T 细胞相关自身免疫和血小板生成素缺乏等。临床表现主要为黏膜皮肤出血，包括瘀点、紫癜、尿或胃肠道黏膜出血、月经过多和鼻出血。治疗的目的是预防出血而不是使血小板计数正常化。一线治疗包括皮质类固醇 +/- 静脉注射免疫球蛋白和抗-D，主要减少抗体介导的血小板破坏并增加外周 Tregs 的数量。二线和后续治疗包括脾切除术、嵌合抗 CD20 抗体（利妥昔单抗），其消除 B 细胞并作为免疫调节剂，以及血小板生成素受体激动剂（罗米司亭），其促进血小板生成。
我们描述了一名 40 岁男性患者，被诊断为免疫性血小板减少症，对一线皮质类固醇和静脉注射免疫球蛋白以及二线罗米司亭单药治疗均无反应。该患者接受了罗米司亭和利妥昔单抗联合治疗，不仅成功治疗了血小板减少症，还导致了 3 级骨痛，随后患者拒绝继续治疗。
利妥昔单抗的常见不良反应是输注反应和长期免疫抑制；罗米司亭的不良反应包括血栓形成、头痛、关节痛-肌痛和胃肠道症状。本例表明，单独使用罗米司亭时没有引起任何明显的副作用，而与利妥昔单抗联合使用则导致严重的骨骼和关节疼痛。我们假设这种联合治疗方案在疗效和不良反应发生概率和/或严重程度方面均具有协同作用。
