Sukumar Senthil, Lämmle Bernhard, Cataland Spero R
Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, CH 3010 Bern, Switzerland.
J Clin Med. 2021 Feb 2;10(3):536. doi: 10.3390/jcm10030536.
Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. TTP results from a severe deficiency of the specific von Willebrand factor (VWF)-cleaving protease, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13). ADAMTS13 deficiency is most commonly acquired due to anti-ADAMTS13 autoantibodies. It can also be inherited in the congenital form as a result of biallelic mutations in the gene. In adults, the condition is most often immune-mediated (iTTP) whereas congenital TTP (cTTP) is often detected in childhood or during pregnancy. iTTP occurs more often in women and is potentially lethal without prompt recognition and treatment. Front-line therapy includes daily plasma exchange with fresh frozen plasma replacement and immunosuppression with corticosteroids. Immunosuppression targeting ADAMTS13 autoantibodies with the humanized anti-CD20 monoclonal antibody rituximab is frequently added to the initial therapy. If available, anti-VWF therapy with caplacizumab is also added to the front-line setting. While it is hypothesized that refractory TTP will be less common in the era of caplacizumab, in relapsed or refractory cases cyclosporine A, -acetylcysteine, bortezomib, cyclophosphamide, vincristine, or splenectomy can be considered. Novel agents, such as recombinant ADAMTS13, are also currently under investigation and show promise for the treatment of TTP. Long-term follow-up after the acute episode is critical to monitor for relapse and to diagnose and manage chronic sequelae of this disease.
血栓性血小板减少性紫癜（TTP）是一种罕见的血栓性微血管病，其特征为微血管病性溶血性贫血、严重血小板减少以及由于富含血小板的微血管血栓导致的缺血性终末器官损伤。TTP是由于特异性血管性血友病因子（VWF）裂解蛋白酶ADAMTS13（一种具有1型血小板反应蛋白重复序列的解整合素和金属蛋白酶，成员13）严重缺乏所致。ADAMTS13缺乏最常见的原因是抗ADAMTS13自身抗体。它也可因该基因的双等位基因突变以先天性形式遗传。在成人中，该病最常为免疫介导性（iTTP），而先天性TTP（cTTP）常在儿童期或孕期被检测到。iTTP在女性中更常见，若不及时识别和治疗可能致命。一线治疗包括每日进行血浆置换并补充新鲜冷冻血浆以及使用皮质类固醇进行免疫抑制。初始治疗常加用针对ADAMTS13自身抗体的人源化抗CD20单克隆抗体利妥昔单抗进行免疫抑制。若有条件，也可在一线治疗中加用抗VWF药物卡泊单抗。虽然据推测在卡泊单抗时代难治性TTP会较少见，但对于复发或难治性病例，可考虑使用环孢素A、N - 乙酰半胱氨酸、硼替佐米、环磷酰胺长春新碱或脾切除术。新型药物，如重组ADAMTS13，目前也在研究中，对TTP的治疗显示出前景。急性发作后的长期随访对于监测复发以及诊断和管理该疾病的慢性后遗症至关重要。
