重组人血小板生成素治疗脓毒症相关血小板减少症患者的临床研究  

Clinical study of recombinant human thrombopoietin in patients with sepsis-associated thrombocytopenia

作　　者：章渭方[1] 方君俊 王国彬[1] 倪昀岚[1] 李惠[1] 龚仕金[2] 虞意华[2] 方堃[3] 舒伟峰[3] 潘孔 寒林玲 郑树森[1] Zhang Weifang Fang Junjun Wang Guobin Ni Junlan Li Hui Gong Shijin Yu Yihua Fang Kun Shu Weifeng Pan Kong Hart Linling Zheng Shusen(Department of Intensive Care Unit, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China Department of Intensive Care Unit, Zhejiang Hospital, Hangzhou 310013, China Department of Intensive Care Unit, Hangzhou Red Cross Hospital, Hangzhou 310003, China Department of Intensive Care Unit, Sir Run shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China)

机构地区：[1]浙江大学医学院附属第一医院重症医学科,杭州310003 [2]浙江医院重症医学科,杭州310013 [3]杭州市红十字会医院重症医学科,杭州310003 [4]浙江大学附属邵逸夫医院重症医学科,杭州310020

出　　处：《中华危重症医学杂志（电子版）》2016年第5期300-308,共9页Chinese Journal of Critical Care Medicine:Electronic Edition

基　　金：浙江省自然基金资助项目(LY15H150001)

摘　　要：目的评估重组人血小板生成素(rhTPO)对严重脓毒症患者伴发血小板减少症患者的疗效。方法将2013年10月至2015年9月期间收治的严重脓毒症合并血小板减少症的患者66例分成实验组(35例)和对照组(31例)。所有患者均予以治疗原发病及积极控制感染,实验组患者于血小板下降的第1天给予rhTPO治疗,300 U·kg-1·d-1,皮下注射,当血小板计数绝对值升高≥50×109/L时即停用,疗程一般不超过14 d。检测所有患者治疗前即刻、治疗后1、2、3、5、7、9、14 d血小板计数、C反应蛋白及丙氨酸转氨酶(ALT)水平。比较两组患者血小板输注例数、急性病生理学和长期健康评价(APACHE)Ⅱ评分、体温下降至正常时间、临床症状消失时间、肺部影像学恢复时间、ICU治疗后28 d病死率及住院时间。记录不良反应发生情况,并比较实验组患者治疗前后活化部分凝血活酶时间、ALT水平、C反应蛋白水平及总胆红素水平。结果实验组患者仅血小板计数治疗后3、5 d较对照组明显升高[(56±19)×109/L vs.(42±18)×109/L,t=3.112,P<0.05;(67±22)×109/L vs.(54±21)×109/L,t=2.520,P<0.05],且实验组患者血小板输注例数明显低于对照组患者(5/35 vs.11/31,χ2=4.022,P=0.045)。两组患者治疗后的APACHEⅡ评分(t=0.692,P<0.05)、体温下降至正常的时间(t=0.510,P<0.05)、临床症状消失时间(t=0.262,P<0.05)、肺部影像系统恢复至正常时间(t=0.685,P<0.05)、28 d病死率(χ2=0.001,P<0.05)及ICU平均住院天数(t=0.637,P<0.05)比较,差异均无统计学意义。同时,研究中没有观察到rhTPO所致的药物不良反应,且经rhTPO治疗前后实验组患者活化部分凝血活酶时间(t=0.697,P<0.05)、ALT(t=0.478,P<0.05)、C反应蛋白(t=0.110,P<0.05)及总胆红素(t=1.634,P<0.05)比较,差异亦均无统计学意义。结论针对脓毒症合并血小板减少症的患者,在传统治疗手段的基础上联合rhTPO治疗可以显著地提升血小板计数,减少输注血Objective To evaluate the efficacy of recombinant human thrombopoietin （rhTPO） in patients with severe sepsis and thrombocytopenia. Methods Sixty-six patients with severe sepsis and brombocytopenia between October 2013 and September 2015 were divided into the experiment group （35 cases） and control group （31 cases）. All patients received primary treatment and infection control. And patients in the experiment group received rhTPO 300U·kg^-1·d^-1 by hypodermic injection, and withdraw when platelet count （PLT） t〉 50×10^9/ L, and the course did not exceed 14 d. Levels of PLT, C-reactive protein and alanine aminotransferase （ALT） were detected before and after the treatment on 1, 2, 3, 5, 7, 9 ans 14 d. The platelet transfusion cases, acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ ）, the time of temperature dropped to normal, time of clinical symptom disappearance, pulmonary imaging recovery time, 28-day fatality rate and length of ICU stay were compared between the two groups. The adverse reactions were recorded, and the activated partial thromboplastin time, levels of ALT, C-reactive protein and total hilirubin were compared before and after treatment in the experiment group. Results The PLT only increased markedly on 3 and 5 d after treatment in the experiment group as compared with those in the control group [（56±19） ×10^9/L vs. （42± 18） ×10^9/L, t=3.112, P〈0.05; （67±22） ×10^9/L vs. （54±21） ×10^9/L, t=2.520, P〈0.05]. The platelet transfusion rate in the experiment group was much lower than that in the control group （5/35 vs. 11/31,X^2=4.022, P=0.045）. However, the APACHEⅡ scores （t=0.692, P〈 0.05）, the time of temperature dropped to normal （t = 0.510, P 〈 0.05）, time of clinical symptom disappearance （t = 0.262, P〈 0.05）, pulmonary imaging recovery time （t = 0.685, P〈 0.05）, 28-day fatality rate （X2 = 0.001, P 〈 0.05） and length of ICU stay （t = 0.637, P 〈 0.05） all showed no significant differences b

关 键 词：重组人血小板生成素 脓毒症 血小板减少 

分 类 号：R459.7[医药卫生—急诊医学] R558.2[医药卫生—治疗学]