我如何治疗免疫型血栓性血小板减少性紫癜

How I treat thrombotic thrombocytopenic purpura

血栓性血小板减少性紫癜(thrombotic thrombocytopenic purpura,TTP)是一种罕见但有致命性的血栓性血液病。TTP分遗传型(hereditary)和免疫型(immune-mediated)。遗传型TTP是由于ADAMTS13(adisintegrin and metalloprotease with thrombospondin-1 repeats,13)基因缺陷所致,而免疫型TTP则由ADAMTS13的自身抗体抑制了其血浆活性所致。准确和及时地对疑诊TTP的患者进行诊断和分型,并将TTP与补体介导的溶血性尿毒症综合征(complement-mediated hemolytic uremic syndrome,cHUS)和其他原因所致的血栓性微血管病(thrombotic microangiopathy)相鉴别,是近年来靶向治疗成功的关键。血浆ADAMTS13活性和抑制物(或自身抗体)的检测对TTP可疑患者的诊断和进一步处理有着极其重要的临床指导意义。三期临床试验和临床实践均表明,血浆置换(therapeutic plasma exchange,TPE)、类固醇皮质激素(corticosteroids)、卡普拉西族单抗(caplacizumab)和利妥昔单抗(rituximab)四联疗法对急性免疫性TTP的治疗有效且安全。这种新疗法,可显著加速血小板计数恢复正常,减少治疗期间病情的反复,并缩短重症监护室和普通病房住院的时间。更重要的是,这种四联疗法可能降低TTP所致的死亡率和持续性微血栓所致的并发症。本文将如何诊断和处理TTP的一些最新进展作一简述。

Thrombotic thrombocytopenic purpura(TTP)is a rare but potentially fatal blood disorder.TTP can be divided into hereditary form and immune-mediated form.Hereditary TTP is caused by ADAMTS13 mutations,while immune TTP is caused by ADAMTS13 autoantibodies that inhibit plasma ADAMTS13 activity.Accurate and timely diagnosis and classification of TTP,and an ability to differentiate TTP from complement-mediated hemolytic uremic syndrome(cHUS)and thrombotic microangiopathy resulting from other causes are crucial for the success of targeted therapy.The detection of plasma ADAMTS13 activity and inhibitors(or autoantibodies)is important for the diagnosis and treatment of patients with suspected TTP.Phase III clinical trials and real-world clinical practice data have demonstrated that therapeutic plasma exchange,corticosteroids,caplacizumab,and rituximab has been shown to be effective and safe for the treatment of acute immune TTP.This new therapy can significantly accelerate the process of platelet count normalization,reduce the recurrence of the disease during treatment,and shorten the time of hospitalization in intensive care unit and general ward.More importantly,this quadruple therapy may reduce the mortality caused by TTP and the complications associated with persistent microvascular thrombosis.This article briefly reviews some of the latest advances in how to diagnose and manage TTP,particularly immune-mediated TTP.