Haemostasis Research Unit, UCL, London, United Kingdom; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
Haemostasis Research Unit, UCL, London, United Kingdom; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom; Cardiometabolic Programme-NIHR UCLH/UC BRC, London, United Kingdom.
Blood Rev. 2022 Sep;55:100945. doi: 10.1016/j.blre.2022.100945. Epub 2022 Feb 17.
Thrombotic thrombocytopenic purpura is an acute life-threatening disorder, associated with a mortality of 90% if unrecognised and untreated. The hallmark is thrombocytopenia and microangiopathic hemolytic anemia, with a blood film characterised by fragmented red cells and end organ damage. The mainstay of treatment is ADAMTS13 replacement, currently with plasma exchange (PEX) and immunosuppression. High dose steroids are used from presentation and anti-CD20 monoclonal antibody therapy, specifically rituximab, is initiated early in the acute disease pathway. The use of the nanobody caplacizumab on confirmation of TTP, by severe ADAMTS13 deficiency (<10iu/dL), has revolutionised acute patient care. Caplacizumab binds the A1 domain, the site on VWF normally occupied by platelets. This results in a quicker normalisation of the platelet count, prevention of exacerbations and refractory disease, reduced PEX and inpatient stay. There is a significant risk of relapse and monitoring of patients allows prophylactic rituximab to be given to prevent further acute admissions.
血栓性血小板减少性紫癜是一种急性危及生命的疾病，如果未被识别和治疗，其死亡率为 90%。其特征是血小板减少症和微血管性溶血性贫血，血涂片表现为破碎的红细胞和终末器官损伤。治疗的主要方法是 ADAMTS13 替代治疗，目前采用血浆置换（PEX）和免疫抑制治疗。从出现症状开始使用大剂量类固醇，并且在急性疾病途径中早期开始使用抗 CD20 单克隆抗体治疗，特别是利妥昔单抗。在 TTP 确诊后，使用纳米抗体 caplacizumab（严重 ADAMTS13 缺乏症(<10iu/dL））极大地改变了急性患者的治疗方式。Caplacizumab 结合 VWF 的 A1 结构域，即血小板通常占据的部位。这导致血小板计数更快地恢复正常，防止病情恶化和难治性疾病，减少 PEX 和住院时间。存在明显的复发风险，对患者进行监测可预防性地给予利妥昔单抗以防止再次急性入院。
