大剂量激素联合重组人血小板生成素与环孢素治疗免疫性血小板减少症的疗效比较
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摘要
目的探讨大剂量激素(GC)联合重组人血小板生成素(rhTPO)和大剂量激素联合环孢素(CsA)两种方案治疗免疫性血小板减少症(ITP)的有效性和安全性。方法选取河南省漯河市中心医院48例ITP患者并随机分为GC+rhTPO组和GC+CsA组,每组24例。两组初期均给予大剂量地塞米松治疗,4 d后停药;GC+rhTPO组同时皮下注射rhTPO,治疗14 d或血小板计数(PLT)正常后减量为2次/周;GC+CsA组同时给予环孢素静脉注射,治疗14 d或PLT正常后减量口服。比较两组患者治疗前、治疗第4、7、14、21和28天PLT和起效时间,计算并比较显效率、有效率及不良反应发生情况。结果不同时间点PLT比较差异有统计学意义(P <0.05),两组PLT比较差异有统计学意义(P <0.05),GC+rhTPO组PLT高于GC+CsA组,两组PLT变化趋势差异有统计学意义(P <0.05);GC+rhTPO组起效时间为(6.5±2.7)d,GC+CsA组起效时间为(9.5±4.5)d,两组比较差异有统计学意义(P<0.05),前者短于后者;GC+rhTPO组显效率和总有效率分别为41.7%和91.7%,GC+CsA组显效率和总有效率分别为12.5%和79.2%,两组显效率比较差异有统计学意义(P<0.05),前者高于后者,两组总有效率比较差异无统计学意义(P>0.05);治疗过程中GC+rhTPO组出现1例不良反应,GC+CsA组出现2例不良反应,均可耐受。结论相对联合CsA治疗,大剂量激素联合rhTPO治疗ITP起效更快、疗效更好,不良反应轻微,但两者均有临床应用价值。
Objective To investigate the efficacy and safety of Glucocorticoid(GC) combined with recombinant human thrombopoietin(rhTPO) or Cyclosporine A(CsA) in the treatment of primary immune thrombocytopenia(ITP). Methods A total of 48 patients diagnosed with ITP were randomly divided into GC+rhTPO group and GC+CsA group. Both groups received intravenous treatment of GC for 4 days. GC+rhTPO group simultaneously received subcutaneous treatment of rhTPO while GC+CsA group received intravenous treatment of CsA. The platelet(PLT) level of the two groups before treatment and 4 days, 7 days, 14 days, 21 days and 28 days after treatment and the effect time were compared. The effective rate, efficancy and adverse reactions of the two groups were calculated and analyzed. Results The PLT levels were different at different points(P < 0.05). The PLT level were different between the GC+rhTPO group and GC+CsA group(P < 0.05). The platelet level of GC+rhTPO group was significantly higher than GC+CsA group(P < 0.05). There was statistically significant difference in variation trends of the two groups(P < 0.05). The effect time of GC+rhTPO group was early than that of GC+CsA group(P < 0.05). The significant effective rate of GC+rhTPO group was higher than that of GC+CsA group(P < 0.05), while the overall effective rates of two groups were not different(P > 0.05). There was 1 patient in GC+rhTPO group and 2 patients in GC+CsA group with side effects. Conclusions GC combined with rhTPO is a more effective treatment and has a faster onset than the treatment of GC combined with CsA.
Objective To investigate the efficacy and safety of Glucocorticoid(GC) combined with recombinant human thrombopoietin(rhTPO) or Cyclosporine A(CsA) in the treatment of primary immune thrombocytopenia(ITP). Methods A total of 48 patients diagnosed with ITP were randomly divided into GC+rhTPO group and GC+CsA group. Both groups received intravenous treatment of GC for 4 days. GC+rhTPO group simultaneously received subcutaneous treatment of rhTPO while GC+CsA group received intravenous treatment of CsA. The platelet(PLT) level of the two groups before treatment and 4 days, 7 days, 14 days, 21 days and 28 days after treatment and the effect time were compared. The effective rate, efficancy and adverse reactions of the two groups were calculated and analyzed. Results The PLT levels were different at different points(P < 0.05). The PLT level were different between the GC+rhTPO group and GC+CsA group(P < 0.05). The platelet level of GC+rhTPO group was significantly higher than GC+CsA group(P < 0.05). There was statistically significant difference in variation trends of the two groups(P < 0.05). The effect time of GC+rhTPO group was early than that of GC+CsA group(P < 0.05). The significant effective rate of GC+rhTPO group was higher than that of GC+CsA group(P < 0.05), while the overall effective rates of two groups were not different(P > 0.05). There was 1 patient in GC+rhTPO group and 2 patients in GC+CsA group with side effects. Conclusions GC combined with rhTPO is a more effective treatment and has a faster onset than the treatment of GC combined with CsA.
引文
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[4]中华医学会血液学分会血栓与止血学组.成人原发免疫性血小板减少症诊断与治疗中国专家共识(2012年版)[J].中华血液学杂志, 2012, 33(11):975-977.
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[6]张颖,刘颖,王新有,等.血小板膜糖蛋白特异性抗体与免疫性血小板减少症患者疗效及出血程度的关系[J].血栓与止血学,2016, 22(4):382-385.
[7]王萌,刘延方,孙慧,等.重组人血小板生成素治疗46例新诊断的免疫性血小板减少症成人患者的临床观察[J].中国实验血液学杂志, 2016, 24(2):531-535.
[8]吴洋.血小板膜糖蛋白去唾液酸化在ITP发病机制中的研究[D].济南:山东大学, 2014.
[9]GROZOVSKY R, BEGONJA A J, LIU K, et al. The AshwellMorell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling[J]. Nat Med, 2015, 21(1):47-54.
[10]NEUNERT C, LIM W, CROWTHER M, et al. The American society of hematology 2011 evidence based practice guideline for immune thrombocytopenia[J]. Blood, 2011, 117(16):4190-4207.
[11]谢研研,杨明珍.地塞米松治疗前后免疫性血小板减少症患者树突状细胞亚群及细胞因子变化的研究[J].安徽医科大学学报, 2016, 51(7):998-1001.
[12]KUTER D J. The biology of thrombopoietin and thrombopoietin receptor agonists[J]. Int J Hematol, 2013, 98(1):10-23.
[13]CREMER M, SCHULZE H, LINTHORST G, et al. Serum levelsofthrombopoietin,IL-11,andIL-6inpediatric thrombocytopenias[J]. Ann Hematol, 1999, 78(9):401.
[14]侯明,纪春岩,朱媛媛,等.血小板减少性疾病患者血浆血小板生成素水平的检测[J].中华医学杂志, 1999(5):36-37.
[15]王书杰,杨仁池,邹萍,等.重组人血小板生成素治疗特发性血小板减少性紫癜的多中心随机对照临床试验[J].血栓与止血学, 2010, 16(4):149-153.
[16]赵永强,王庆余,翟明,等.重组人血小板生成素治疗慢性难治性特发性血小板减少性紫癜的多中心临床试验[J].中华内科杂志, 2004(8):58-60.
[17]杜以萍,张充力,毕珍宁.糖皮质激素联合重组人促血小板生成素治疗特发性血小板减少性紫癜[J].血栓与止血学, 2014,20(2):79-80.
[18]刘一,吕欣,董振香.重组人血小板生成素的药理作用和临床评价[J].中国新药杂志, 2008(3):254-258.
[19]OLSSONB, ANDERSSONPO,JERNSM,etal.T-cellmediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura[J]. Nat Med, 2003, 9(9):1123-1124.
[2]郭宏岗,王佳佳,岑坚,等.地塞米松联合血小板生成素及环孢素治疗免疫性血小板减少症的疗效观察[J].转化医学杂志,2016, 5(5):279-282.
[3]章波,栾佐.慢性难治性原发免疫性血小板减少症治疗进展[J].儿科药学杂志, 2015, 21(3):52-56.
[4]中华医学会血液学分会血栓与止血学组.成人原发免疫性血小板减少症诊断与治疗中国专家共识(2012年版)[J].中华血液学杂志, 2012, 33(11):975-977.
[5]SEGAL J B, POWE N R. Prevalence of immune thrombocytopenia:analyses of administrative data[J]. J Thromb Haemost, 2006, 4(11):2377-2383.
[6]张颖,刘颖,王新有,等.血小板膜糖蛋白特异性抗体与免疫性血小板减少症患者疗效及出血程度的关系[J].血栓与止血学,2016, 22(4):382-385.
[7]王萌,刘延方,孙慧,等.重组人血小板生成素治疗46例新诊断的免疫性血小板减少症成人患者的临床观察[J].中国实验血液学杂志, 2016, 24(2):531-535.
[8]吴洋.血小板膜糖蛋白去唾液酸化在ITP发病机制中的研究[D].济南:山东大学, 2014.
[9]GROZOVSKY R, BEGONJA A J, LIU K, et al. The AshwellMorell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling[J]. Nat Med, 2015, 21(1):47-54.
[10]NEUNERT C, LIM W, CROWTHER M, et al. The American society of hematology 2011 evidence based practice guideline for immune thrombocytopenia[J]. Blood, 2011, 117(16):4190-4207.
[11]谢研研,杨明珍.地塞米松治疗前后免疫性血小板减少症患者树突状细胞亚群及细胞因子变化的研究[J].安徽医科大学学报, 2016, 51(7):998-1001.
[12]KUTER D J. The biology of thrombopoietin and thrombopoietin receptor agonists[J]. Int J Hematol, 2013, 98(1):10-23.
[13]CREMER M, SCHULZE H, LINTHORST G, et al. Serum levelsofthrombopoietin,IL-11,andIL-6inpediatric thrombocytopenias[J]. Ann Hematol, 1999, 78(9):401.
[14]侯明,纪春岩,朱媛媛,等.血小板减少性疾病患者血浆血小板生成素水平的检测[J].中华医学杂志, 1999(5):36-37.
[15]王书杰,杨仁池,邹萍,等.重组人血小板生成素治疗特发性血小板减少性紫癜的多中心随机对照临床试验[J].血栓与止血学, 2010, 16(4):149-153.
[16]赵永强,王庆余,翟明,等.重组人血小板生成素治疗慢性难治性特发性血小板减少性紫癜的多中心临床试验[J].中华内科杂志, 2004(8):58-60.
[17]杜以萍,张充力,毕珍宁.糖皮质激素联合重组人促血小板生成素治疗特发性血小板减少性紫癜[J].血栓与止血学, 2014,20(2):79-80.
[18]刘一,吕欣,董振香.重组人血小板生成素的药理作用和临床评价[J].中国新药杂志, 2008(3):254-258.
[19]OLSSONB, ANDERSSONPO,JERNSM,etal.T-cellmediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura[J]. Nat Med, 2003, 9(9):1123-1124.