阿伐曲泊帕联合重组人血小板生成素和阿伐曲泊帕单药治疗慢性肝病相关重度血小板减少症的临床疗效

Clinical efficacy of avatrombopag combined with recombinant human thrombopoietin versus avatrombopag in the treatment of severe thrombocytopenia associated with chronic liver disease

目的探讨阿伐曲泊帕联合重组人血小板生成素(rhTPO)和阿伐曲泊帕单药治疗慢性肝病相关重度血小板减少症(TCP)的临床疗效。方法采用回顾性队列研究方法。收集2020年5月至2021年10月中国科学技术大学附属第一医院收治的56例慢性肝病相关重度TCP患者的临床资料;男36例, 女20例;中位年龄54岁, 年龄范围为33~74岁。56例患者中, 21例采用阿伐曲泊帕联合rhTPO方案设为联合治疗组, 35例采用阿伐曲泊帕单药方案设为单药治疗组。观察指标:(1)用药后血小板(PLT)变化情况。(2)药物不良反应情况。采用门诊和电话方式进行随访, 监测患者治疗后2周内PLT的变化情况, 了解患者治疗效果。随访时间截至2021年10月。正态分布的计量资料以x±s表示, 组间比较采用t检验;偏态分布的计量资料以M(范围)表示, 组间比较采用Mann-WhitneyU检验。计数资料以绝对数或百分比表示, 组间比较采用χ^(2)检验或Fisher确切概率法。重复测量数据采用重复测量方差分析。结果 (1)用药后PLT变化情况:联合治疗组患者用药后1~5 d PLT为(35±19)×109/L, 用药后6~10 d PLT为(73±41)×109/L;单药治疗组上述指标分别为(40±30)×109/L, (70±51)×109/L。两组患者用药前后PLT组间变化趋势比较, 差异无统计学意义(F组间=0.30, P>0.05);两组患者用药前后PLT变化趋势比较, 差异有统计学意义(F时间=59.96, P<0.05);两组患者PLT变化趋势之间无交互效应(F交互=0.40, P>0.05)。联合治疗组患者治疗有效率为66.67%(14/21), 单药治疗组为54.29%(19/35), 两组患者治疗有效率比较, 差异无统计学意义(χ^(2)=0.83, P>0.05)。(2)药物不良反应情况:联合治疗组患者发生头痛、头晕、输血反应、血尿、蛋白尿、发热、腹痛、腹泻、消化不良、疲劳、恶心、外周组织水肿例数分别为2、4、1、2、2、7、10、6、8、14、12、5例, 单药治疗组患者上述指标分别为5、8、1、3、5、7、19、11、20、19、14、5例, 两组患者头痛、头晕、输血反应、血尿、蛋白尿比较, 差异均无统计学意义(P>0.05);两组患者发热、腹痛、腹泻、消化不良、疲劳、恶心、外周组织水肿比较, 差异均无统计学意义(χ^(2)=1.24, 0.23, 0.05, 1.91, 0.83, 2.04, 0.81, P>0.05)。结论阿伐曲泊帕联合rhTPO方案和阿伐曲泊帕单药方案均能升高慢性肝病相关重度TCP患者PLT;与阿伐曲泊帕单药方案比较, 阿伐曲泊帕联合rhTPO方案并未带来更佳的临床获益。

Objective To investigate the clinical efficacy of avatrombopag combined with recombinant human thrombopoietin(rhTPO)versus avatrombopag in the treatment of severe thrombocytopenia associated with chronic liver disease.Methods The retrospective cohort study was conducted.The clinical data of 56 patients with severe thrombocytopenia associated with chronic liver disease who were admitted to the First Affiliated Hospital of University of Science and Technology of China from May 2020 to October 2021 were collected.There were 36 males and 20 females,aged from 33 to 74 years,with a median age of 54 years.Of 56 patients,21 cases undergoing treatment of avatrombopag combined with rhTPO were allocated into the combined treatment group and 35 cases undergoing treatment of avatrombopag were allocated into the monotherapy group.Observation indicators:(1)changes of platelet after treatment;(2)adverse drug reaction.Follow-up was conducted using outpatient examination and telephone interview to detect changes of platelet and effects of treatment within 2 weeks after treatment.The follow-up was up to October 2021.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were represented as M(range),and comparison between groups was analyzed using the Mann-Whitney U test.Count data were described as absolute numbers or percentages,and compari-son between groups was analyzed using the chi-square test or Fisher exact probability.Repeated measurement data were analyzed using the repeated ANOVA.Results(1)Changes of platelet after treatment.The platelet level within 1 to 5 days and 6 to 10 days after treatment in the combined treatment group were(35±19)×109/L and(73±41)×109/L,respectively.The above indicators of the monotherapy group were(40±30)×109/L and(70±51)×109/L,respectively.There was no significant difference in change trends of platelet before and after treatment between the two groups(Fgroup=0.30,P>0.05).There was a significant difference in platelet count before and after treatment between the two groups(Ftime=59.96,P<0.05).There was no interaction effect in change trends of platelet between the two groups(Finteraction=0.40,P>0.05).The effective rates were 66.67%(14/21)in the combination therapy group and 54.29%(19/35)in the monotherapy group.There was no significant difference in the effective rate between the two groups(χ²=0.83,P>0.05).(2)Adverse drug reaction.Cases with headache,dizziness,blood transfusion reaction,hematuria,proteinuria,fever,abdominal pain,diarrhea,dyspepsia,fatigue,nausea or peripheral tissue edema were 2,4,1,2,2,7,10,6,8,14,12,5 in the combined treatment group,versus 5,8,1,3,5,7,19,11,20,19,14,5 in the monotherapy group,respectively.There was no significant difference in cases with headache,dizziness,blood transfusion reaction,hematuria,proteinuria between the two groups(P>0.05),and there was no significant difference in cases with fever,abdominal pain,diarrhea,dyspepsia,fatigue,nausea,peripheral tissue edema between the two groups(χ²=1.24,0.23,0.05,1.91,0.83,2.04,0.81,P>0.05).Conclusion Both of avatrombopag combined with rhTPO and monotherapy of avatrom-bopag can be used to promote the platelet level in patients with severe thrombocytopenia associated with chronic liver disease,and avatrombopag combined with rhTPO does not provide better clinical benefits compared with monotherapy avatrombopag.