Cataland Spero R, Wu Haifeng M
Departments of Internal Medicine and Pathology, Ohio State University College of Medicine and Public Health, Columbus, OH 43210-1240, USA.
Curr Opin Hematol. 2005 Sep;12(5):359-63. doi: 10.1097/01.moh.0000170534.33517.99.
This review focuses on recent advances in the use of immune-based therapy to treat patients with refractory and relapsing acquired thrombotic thrombocytopenic purpura.
Advances in understanding of the pathophysiology of idiopathic thrombotic thrombocytopenic purpura have provided the rationale for immune-based treatment approaches to refractory and relapsing cases of thrombotic thrombocytopenic purpura. The demonstration that a severe deficiency of von Willebrand factor-cleaving protease activity in acquired thrombotic thrombocytopenic purpura is due to an autoantibody inhibitor of the von Willebrand factor-cleaving protease argues for targeting the antibody inhibitor of the von Willebrand factor-cleaving protease with immunosuppressive therapy as a means of increasing protease activity and inducing a sustained remission of the disease. Recent publications, largely case reports and small series of patients, have suggested a role for rituximab and cyclosporine in cases refractory to plasma exchange or resistant to the tapering of plasma exchange therapy.
In the future, a better understanding of the relation between the von Willebrand factor-cleaving protease activity, the nature and titer of von Willebrand factor-cleaving protease inhibitors, and the risk of relapse of thrombotic thrombocytopenic purpura will be important to further validate the strategy of targeting the von Willebrand factor-cleaving protease inhibitory antibody as an effective means of treating acquired thrombotic thrombocytopenic purpura. Prospective data from carefully designed clinical trials are needed to define the effectiveness of specific immunosuppressive therapies at suppressing antibody inhibitors of von Willebrand factor-cleaving protease, improving von Willebrand factor-cleaving protease activity, and inducing a sustained remission of the disease.
本综述聚焦于基于免疫的疗法在治疗难治性和复发性获得性血栓性血小板减少性紫癜患者方面的最新进展。
对特发性血栓性血小板减少性紫癜病理生理学认识的进展为针对难治性和复发性血栓性血小板减少性紫癜病例的基于免疫的治疗方法提供了理论依据。获得性血栓性血小板减少性紫癜中血管性血友病因子裂解蛋白酶活性严重缺乏是由于血管性血友病因子裂解蛋白酶的自身抗体抑制剂所致，这表明采用免疫抑制疗法靶向血管性血友病因子裂解蛋白酶的抗体抑制剂，以此增加蛋白酶活性并诱导疾病持续缓解。近期的出版物，主要是病例报告和小系列患者研究，提示利妥昔单抗和环孢素在对血浆置换难治或对血浆置换疗法减量有抵抗的病例中发挥作用。
未来，更好地理解血管性血友病因子裂解蛋白酶活性、血管性血友病因子裂解蛋白酶抑制剂的性质和滴度与血栓性血小板减少性紫癜复发风险之间的关系，对于进一步验证靶向血管性血友病因子裂解蛋白酶抑制性抗体作为治疗获得性血栓性血小板减少性紫癜有效手段的策略至关重要。需要精心设计的临床试验的前瞻性数据来确定特定免疫抑制疗法在抑制血管性血友病因子裂解蛋白酶抗体抑制剂、提高血管性血友病因子裂解蛋白酶活性以及诱导疾病持续缓解方面的有效性。
