背景:移植相关血栓性微血管病(TA-TMA)是一种与补体通路过度激活有关的内皮损伤综合征。表现为微血管病性溶血性贫血,消耗性血小板减少症,和微血管血栓形成导致缺血性组织损伤。真菌和病毒上的甘露糖残基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触发TA-TMA的原因之一。Narsoplimab,靶向MASP-2的人单克隆抗体是凝集素途径的有效抑制剂。我们描述了一名儿科患者的移植过程,该患者在念珠菌触发的巨噬细胞激活综合征后发展为TA-TMA,并接受了Narsoplimab治疗。数据收集是前瞻性的。
方法:6岁女孩接受了人类白细胞抗原(HLA)单倍体相合造血干细胞移植,移植后使用环磷酰胺治疗严重再生障碍性贫血。在移植的第二周,患者出现巨噬细胞活化综合征,需要接受类固醇和静脉注射免疫球蛋白治疗.随后,USG腹部和血液真菌PCR显示肝脾念珠菌病的诊断。念珠菌触发的巨噬细胞活化综合征对抗真菌药物有反应,类固醇,静脉注射免疫球蛋白,和阿仑珠单抗。然而,随后的临床过程并发血栓性微血管病.患者在第2周出现高血压,其次是高乳酸脱氢酶(1010U/L),分裂细胞(每hpf5个),低触珠蛋白(<5mg/dl),血小板减少症,第三周贫血。停用了环孢素,患者接受了10天的去纤肽治疗,无反应。该过程因胃肠道和肾脏的参与而进一步复杂化。她每次直肠出血,大便频繁但容量少,严重的腹痛,和低白蛋白血症,尿蛋白:肌酐比值升高。Narsoplimab在移植的第5周开始。开始Narsoplimab后观察到乳酸脱氢酶下降。随后是胃肠道症状的解决,蛋白尿,和血细胞减少的恢复。TA-TMA的第二次发作与细小病毒血症一起发生,并且也成功地用Narsoplimab治疗。
结论:凝集素途径抑制可用于治疗移植相关血栓性微血管病的致命并发症。
BACKGROUND: 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.
METHODS: 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.
CONCLUSIONS: Lectin pathway inhibition could be useful in treating the fatal complication of transplant-associated thrombotic microangiopathy.