Pandrowala Ambreen, Ganatra Parth, Krishnan V P, Sharma Ajay Narayan, Chavan Saroj, Bodhanwala Minnie, Agarwal Bharat, Hiwarkar Prashant
Department of Blood and Marrow Transplantation, Bai Jerbai Wadia Hospital for Children, Acharya Donde Marg, Mumbai, 400012, India.
Department of Pediatric Radiology, Bai Jerbai Wadia Hospital for Children, Acharya Donde Marg, Mumbai, 400012, India.
Thromb J. 2023 Mar 13;21(1):26. doi: 10.1186/s12959-023-00464-9.
Transplantation-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome linked to the overactivation of complement pathways. It manifests with microangiopathic hemolytic anemia, consumptive thrombocytopenia, and microvascular thrombosis leading to ischemic tissue injury. Mannose residues on fungi and viruses activate the mannose-binding lectin complement pathway, and hence activation of the lectin pathway could be one of the reasons for triggering TA-TMA. Narsoplimab, a human monoclonal antibody targeting MASP-2 is a potent inhibitor of the lectin pathway. We describe the transplant course of a pediatric patient who developed TA-TMA following Candida-triggered macrophage activation syndrome and was treated with Narsoplimab. The data collection was performed prospectively.
The six-year-old girl underwent a human leucocyte antigen (HLA) haploidentical hematopoietic stem cell transplant using post-transplant Cyclophosphamide for severe aplastic anemia. In the second week of the transplant, the patient developed macrophage activation syndrome necessitating treatment with steroids and intravenous immunoglobulin. Subsequently, USG abdomen and blood fungal PCR revealed the diagnosis of hepatosplenic candidiasis. Candida-triggered macrophage activation syndrome responded to antifungals, steroids, intravenous immunoglobulin, and alemtuzumab. However, the subsequent clinical course was complicated by thrombotic microangiopathy. The patient developed hypertension in the 2nd week, followed by high lactate dehydrogenase (1010 U/L), schistocytes (5 per hpf), low haptoglobin (< 5 mg/dl), thrombocytopenia, and anemia in the 3rd week. Ciclosporin was stopped, and the patient was treated with 10 days of defibrotide without response. The course was further complicated by the involvement of the gastrointestinal tract and kidneys. She had per rectal bleeding with frequent but low-volume stools, severe abdominal pain, and hypoalbuminemia with a rising urine protein:creatinine ratio. Narsoplimab was started in the 5th week of the transplant. A fall in lactate dehydrogenase was observed after starting Narsoplimab. This was followed by the resolution of gastrointestinal symptoms, proteinuria, and recovery of cytopenia. The second episode of TA-TMA occurred with parvoviraemia and was also successfully treated with Narsoplimab.
Lectin pathway inhibition could be useful in treating the fatal complication of transplant-associated thrombotic microangiopathy.
移植相关血栓性微血管病（TA-TMA）是一种与补体途径过度激活相关的内皮损伤综合征。其表现为微血管病性溶血性贫血、消耗性血小板减少以及导致缺血性组织损伤的微血管血栓形成。真菌和病毒上的甘露糖残基可激活甘露糖结合凝集素补体途径，因此凝集素途径的激活可能是引发TA-TMA的原因之一。那西普明单抗是一种靶向MASP-2的人源单克隆抗体，是凝集素途径的强效抑制剂。我们描述了一名儿科患者的移植过程，该患者在念珠菌引发巨噬细胞活化综合征后发生TA-TMA，并接受了那西普明单抗治疗。数据收集是前瞻性进行的。
这名6岁女孩因严重再生障碍性贫血接受了单倍体相合造血干细胞移植，并使用移植后环磷酰胺。在移植的第二周，患者出现巨噬细胞活化综合征，需要使用类固醇和静脉注射免疫球蛋白进行治疗。随后，腹部超声和血液真菌聚合酶链反应（PCR）显示诊断为肝脾念珠菌病。念珠菌引发的巨噬细胞活化综合征对抗真菌药、类固醇、静脉注射免疫球蛋白和阿仑单抗有反应。然而，随后的临床病程因血栓性微血管病而复杂化。患者在第2周出现高血压，随后在第3周出现高乳酸脱氢酶（1010 U/L）、裂体细胞（每高倍视野5个）、低触珠蛋白（<5 mg/dl）、血小板减少和贫血。停用环孢素，患者接受了10天的去纤苷治疗但无反应。病程因胃肠道和肾脏受累而进一步复杂化。她出现直肠出血，大便频繁但量少，严重腹痛，低白蛋白血症，尿蛋白：肌酐比值升高。在移植的第5周开始使用那西普明单抗。开始使用那西普明单抗后观察到乳酸脱氢酶下降。随后胃肠道症状、蛋白尿得到缓解，血细胞减少症恢复。TA-TMA的第二次发作与细小病毒血症有关，也成功地用那西普明单抗进行了治疗。
凝集素途径抑制可能有助于治疗移植相关血栓性微血管病的致命并发症。
