艾曲波帕联合硫唑嘌呤治疗难治性特发性血小板减少性紫癜的疗效及其对细胞免疫功能的影响研究

doi:10.12114/j.issn.1007-9572.2018.00.450

摘要/Abstract

摘要： 背景　难治性特发性血小板减少性紫癜（RITP）的治疗一直是临床的一大难题，目前尚无统一的安全有效的治疗方案，且对于部分血小板计数（PLT）极度下降的患者有致死的出血风险。艾曲波帕作为升血小板的新药，为RITP的治疗提供了一个安全有效的治疗方法。目的　探究艾曲波帕联合硫唑嘌呤治疗RITP的疗效，并观察其对细胞免疫功能的影响。方法　选择2013年1月—2018月1月在绍兴市人民医院血液科住院治疗的46例RITP患者，依据随机数字表法将其分为治疗组和环孢素（CSA）组，各23例。另选取同期在本院进行体检的健康者25例作为对照组。治疗组患者给予艾曲波帕联合硫唑嘌呤治疗；CSA组患者给予环孢素联合达那唑治疗。治疗3个月进行疗效评价。比较治疗组与CSA组临床疗效。收集治疗组和CSA组患者治疗前和治疗3个月外周血Th1细胞因子〔白介素（IL）-2、γ干扰素（IFN-γ）〕和Th2细胞因子（IL-4、IL-5）、B1淋巴细胞（CD+19淋巴细胞百分数、CD5+CD+19淋巴细胞百分数）、PLT，并与对照组比较。记录治疗组和CSA组患者不良反应发生情况。结果　治疗组患者总有效率为69.9%（16/23），CSA组患者总有效率为73.9%（17/23）；两组患者总有效率比较，差异无统计学意义（χ2=0.107，P=0.743）。治疗组、CSA组患者治疗前IL-2、IFN-γ、CD+19淋巴细胞百分数、CD5+CD+19淋巴细胞百分数高于对照组，IL-4、IL-5、PLT低于对照组（P<0.05）；治疗组、CSA组患者治疗3个月IL-2、IFN-γ、CD+19淋巴细胞百分数、CD5+CD+19淋巴细胞百分数低于本组治疗前，IL-4、IL-5、PLT高于本组治疗前（P<0.05）。治疗组8例患者发生肝功能损伤，CSA组16例患者发生肝功能损伤；治疗组患者肝功能损伤发生率（34.8%）低于CSA组（69.6%）（χ2=6.527，P=0.013）。结论　艾曲波帕联合硫唑嘌呤治疗RITP，安全有效，患者耐受性好；艾曲波帕联合硫唑嘌呤可能通过调节RITP患者外周血Th淋巴细胞及B1淋巴细胞，进而促进血小板生成，从而发挥治疗作用。

关键词: 紫癜, 血小板减少性, 特发性；艾曲波帕；硫唑嘌呤；T细胞抗原受体特异性

Abstract: Background　The treatment of refractory immune thrombocytopenic purpura（RITP） has always been a major clinical problem.At present，there is no unified safe and effective treatment，and there is a risk of death for some patients with extremely low platelet count.Eltrombopag，as a new drug for increased platelet counts，provides a safe and effective treatment for RITP.Objective　To study the efficacy of Eltrombopag combined with Azathioprine in the treatment of RITP and its effect on cellular immune function.Methods　A total of 46 patients with RITP who were hospitalized in Hematology Department of Shaoxing People's Hospital from January 2013 to January 2018 were selected.They were randomly divided into treatment group and cyclosporine（CSA） group，each with 23 cases.Another 25 healthy persons who had physical examination in our hospital during the same period were selected as the control group.Patients in the treatment group were treated with Eltrombopag combined with Azathioprine.The CSA group was treated with Cyclosporine combined with Danazol.Therapeutic effect was evaluated after 3 months of treatment.The clinical effects of treatment group and CSA group were compared.Th1 cytokines（IL-2，IFN-γ） and Th2 cytokines（IL-4，IL-5），B1 lymphocyte（percentage of CD+19 lymphocyte and CD5+CD+19 lymphocyte），PLT in peripheral blood of treatment group and CSA group were collected before treatment and 3 months after treatment，and compared with the control group.The adverse reactions in the treatment group and CSA group were recorded.Results　The total effective rate was 69.9%（16/23） in the treatment group and 73.9%（17/23） in the CSA group.There was no significant difference in the total effective rate between the two groups（χ2=0.107，P=0.743）．Before treatment，the percentage of IL-2，IFN-γ，CD+19 lymphocyte and CD5+CD+19 lymphocyte in the treatment group and CSA group was higher than that in the control group，while the number of IL-4 and IL-5 and platelet count in the treatment group and CSA group was lower than that in the control group（P<0.05）．After 3 months of treatment，the percentage of IL-2，IFN-γ，CD+19 lymphocyte and CD5+CD+19 lymphocyte in the treatment group and CSA group was lower than that before treatment，while the number of IL-4 and IL-5 and platelet count was higher than that before treatment（P<0.05）．Eight patients in the treatment group and 16 patients in the CSA group suffered from liver function injury.The incidence of liver function injury in the treatment group（34.8%） was lower than that in the CSA group（69.6%），and the difference was statistically significant（χ2=6.527，P=0.013）．Conclusion　Eltrombopag combined with Azathioprine in the treatment of RITP is safe，effective and well tolerated.Eltrombopag combined with Azathioprine may play a therapeutic role by regulating Th lymphocyte and B1 lymphocyte in peripheral blood of patients with RITP，thereby promoting platelet formation.

Key words: Purpura, thrombocytopenic, idiopathic；Eltrombopag；Azathioprine；T-cell antigen receptor specificity

罗洪强,钟永根,封蔚莹. 艾曲波帕联合硫唑嘌呤治疗难治性特发性血小板减少性紫癜的疗效及其对细胞免疫功能的影响研究[J]. 中国全科医学, 2019, 22(21): 2588-2592. DOI: 10.12114/j.issn.1007-9572.2018.00.450.
LUO Hongqiang,ZHONG Yonggen,FENG Weiying. Efficacy of Eltrombopag Combined with Azathioprine in the Treatment of Refractory Immune Thrombocytopenic Purpura and Its Effect on Cellular Immune Function　[J]. Chinese General Practice, 2019, 22(21): 2588-2592. DOI: 10.12114/j.issn.1007-9572.2018.00.450.

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