儿童血栓性血小板减少性紫癜的特点和治疗现状

The characteristics and current treatment status of child-onset thrombotic thrombocytopenic purpura

血栓性血小板减少性紫癜(thromboticthrombocytopenicpurpura,TTP)是一种属于血栓性微血管病的少见但致命的疾病,病理生理基础是特异性血管性假性血友病因子(VWF)裂解蛋白酶——含有1型血栓反应蛋白重复序列的解整联蛋白和金属蛋白酶A成员13(ADAMTS-13)的功能严重缺乏,这种缺乏可以是先天性或获得性。TTP的临床表现与其他血栓性微血管病类似,特征为血栓性微血管病性溶血、血小板减少和器官功能损害,难以与其他血栓性微血管病鉴别。血浆ADAMTS-13活性<10%是唯一可确定TTP诊断的方法。TTP急性期一线治疗以血浆治疗为基础。先天性TTP可从预防性血浆治疗获益。获得性TTP需联合激素、B细胞消耗疗法和血浆置换治疗。对TPP患者必须长期随访,且必须包括ADAMTS-13活性监测。ADAMTS-13活性<10%预示TTP复发,以利妥昔单抗行预防性B细胞消耗治疗可用于预防获得性TTP复发。

Thrombotic thrombocytopenic purpura (TTP) is a rare but fatal entity of thrombotic microangiopathies(TMAs). The pathophysiology of the disease is based on a severe functional deficiency of a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS-13), the specific von Willebrand factor (VWF)-cleavage protease.This deficiency may be either acquired or congenital.The clinical manifestations of TTP include microangiopathic hemolytic anemia, thrombocytopenia and dysfunction of involved organs, which are similar to other TMAs.The differential diagnosis with other TMAs may be challenging.The activity of plasma ADAMTS-13 <10% is the only definitive method for diagnosis of TTP.The first-line treatment of the acute phase of TTP is based on plasmatherapy.In congenital TTP, patients benefit from a prophylactic plasmatherapy.In acquired TTP, steroids and B-cells depleting therapies are increasingly used together with plasma exchange.Long-term follow-up including the monitoring of ADAMTS-13 activity is mandatory.A severe decrease in ADAMTS-13 activity (<10%) may predict relapses and preemptive B-cell depletion with rituximab can be used to prevent relapses of acquired TTP.