免疫性血小板减少性紫癜分型施治的基础与临床研究进展

Recent Progress of Study on Mechanism of Immune Thrombocytopenic Purpura and Its Clinical Treatment——Review

免疫性血小板减少性紫癜(ITP)的发病涉及血小板免疫性破坏增多和骨髓巨核细胞产生血小板过少两个方面。经典的ITP治疗只涉及抑制血小板免疫破坏的一个方面,即采用免疫抑制剂如糖皮质激素、免疫球蛋白和抗-D抗体(针对Rh系统D抗原的抗体),也有采用长春新碱或抗人CD20单克隆抗体清除B淋巴细胞,以及环孢菌素等免疫抑制剂等。对难治性病例还要进行脾脏切除手术。虽然免疫抑制治疗方案对大多数患者治疗有效,但30%以上的ITP患者会复发,且这类治疗不良反应较多,脾脏切除还会导致机体免疫力下降,容易出现感染等并发症。临床需要更加安全有效的治疗方法。重组人血小板生成素(TPO)由于自身抗体而继发严重的血小板,目前已退出ITP的治疗。最近,欧洲批准了2个血小板受体激活剂AMG 531和Eltrombopag,通过促进巨核细胞分化和血小板生成来治疗ITP。国内采用泛细胞保护剂为主的联合方案治疗难治/复发性ITP也取得了良好的效果。总之,根据ITP患者不同的发病机理进行个体化治疗是未来ITP基础与临床的研究方向。本文就ITP的发病机理和临床治疗作一综述,并对ITP分型施治的可能性进行了初步的探讨。

Immune thrombocytopenia purpura （ITP） is a disorder mediated by antiplatelet antibodies and characterized by accelerated destruction of platelets and impaired platelet production. The mainstay therapies for ITP have included corticosteroids, the immune globulin intravenous immunoglobulin and IV anti-D （ monoclonal antibodies against the D antigen of the Rh system）, vinblastine or a monoclonal anti-CD20 antibody that transiently depletes CD20 ^＋ B cells, danazol, cyelophosphamide and even splenectomy to refractory one. Most of ITP patients responsed to those treatment, while more than 30% of whom may relapse sooner or later. The recombinant forms of human TPO were discontinued from human use in clinic because recipients of these agents developed significant thrombocytopenia secondary to production of neutralizing antibodies that cross-reacted with endogenous TPO. All above mentioned treatments have side effects and severe infection may arise post splenectomy. The more powerful treatment with less side effects are needed. There are two TPO receptor agonist, AMG531 and Eltrompobag, have approved in Europe for the treatment of ITP. Both of them can improve the differentiation of megakaryocyte and platelets production. Combination treatment including pancytoprotector shows good effect in the treatment of refractory and relapsed ITP in China. Altogether, individual treatment of ITP is the contemporary trend in both clinical and preclinical practice. In this review the pathogenesis of ITP and its clinical therapies were reviewed, the individual regiments for treating ITP patients were discussed.