重组人血小板生成素治疗脓毒症血小板减少症

目的 评价重组人血小板生成素(recombinant human thromobopoietin,rhTPO)对脓毒症相关血小板减少症的疗效和安全性.方法 前瞻、对照方法观察2009年1月至2009年11月入住天津市第一中心医院ICU的脓毒症并发生血小板减少的患者,外周血血小板计数≤40×109 L-1且主治及以上医师认为有必要升高血小板治疗的脓毒症患者为研究对象,排除恶性肿瘤、6个月内接受过免疫调节剂治疗、年龄＜14岁或＞75岁、心肺复苏后、入院24 h内转出或死亡者及终末期肝或肾功能衰竭者.将入选43例患者根据"不平衡指数最小的分配原则"随机分为特比奥(rhTPO)组(21例)和静脉注射用人免疫球蛋白(Intravenous Immunoglobulin,IVIG)组(22例),rhTPO组在综合治疗的基础上加用特比奥300 U·kg-1·d-1,2～8 d,IVIG组则在综合治疗的基础上加用静脉注射用人免疫球蛋白400 mg·kg-1·d-1,连用5 d.观察比较两组患者治疗后第1,2,3,5,7天外周静脉血血小板计数以及凝血指标、肝肾功能、出血及血制品输注情况、ICU住院时间、治疗费用等指标,随访并比较28 d病死率等预后情况.两组间参数的比较采用独立样本t检验,计数资料进行χ2检验.结果 rhTPO组治疗后血小板恢复最高值明显高于IVIG组(t=2.21,P=0.032);rhTPO组血小板最低值和最高值的差值明显大于IVIG组(t=7.40,P＜0.001).治疗前两组血小板计数差异无统计学意义(t=0.458,P＞0.05),用药第2天、第3天rhTPO组血小板计数升高明显高于IVIG组(t=2.166和t=2.132,P=0.036和P=0.041),两组存活病例用药第3天rhTPO组血小板计数明显高于IVIG组(t=2.28,P=0.032),两组出血发生率差异无统计学意义(χ2=0.720,P＞0.05),但rhTPO组血小板及血浆输注量明显少于IVIG组(t=2.038和t=2.252,P=0.048和P=0.030).两组ICU住院时间及病死率差异无统计学意义(t=0.91和χ2=0.264,P＞0.05),但rhTPO组用药平均消费显著低于IVIG组(t=16.93,P＜0.001).所有病死病例治疗前血小板计数显著低于存活组(t=3.448,P=0.001).rhTPO组无一例发生不良反应.结论 重组人血小板生成素可促进脓毒症相关血小板减少症血小板计数的恢复,减少患者血制品输注量,降低医疗费用且安全可靠.

Abstract：

Objective To evaluate the efficacy and safety of rhTPO (recombinant human thromobopoietin) employed for the treatment of sepsis-associated thrombocytopenia. Method There were 47 patients with sepsis-associaiod thrombocytopcnia eligible for the prospective, randomized (random number) and controlled clinical study from January 2009 to November 2009 in ICU of the Tianjin First center Hospital. According to the principle of minimum distribution imbalance index, these patients were randomly divided into the rhTPO group (n = 21) and the IVIG (intravenous immunoglobulin) control group (n = 22). In the rhTPO group, rhTPO was given subcutaneously to patients in a dose of 300 U/kg/d for 2 ～ 8 d, and in the IVIG control group, IVIG was used instead of rhTPO in a dose of 400 mg/kg/d for 5 days. Laboratory tests included blood routine examination, hepatic function, kidney function, coagulation function. The amount of blood products used, bleeding events, the days of ICU and hospital stay, total therapy cost and 28-day mortality were compared between two groups. Results The maximal platelet count in the rhTPO group was significantly higer than that in the contral group (t = 2.21, P =0.032). The mean value of difference between minimal and maximal platelet counts in the rhTPO group was much higher than that in the control group (t =7.40, P ＜0. 001). The average platelet count was no statistical difference between two groups before treatment (t =0. 458, P ＞ 0.05), but the average platelet counts in the rhTPO group were significantly higer than those in the contral group on the second and third day after treatment(t = 2. 166 and t = 2. 132, P =0. 036 and P =0.041. There were no statistical differences in incidence of bleeding, length of ICU stay and mortality between two groups (χ2 =0.720, t =0.91 and χ2 =0.264, P ＞0.05) , but the amounts of plasma and platelet transfusion were significantly less in the rhTPO group than those in the control group (t = 2.038 and t =2.252, P=0.048 and P=0.030) and the medical cost was cut down significantly in rhTPO group (t = 16.93, P ＜ 0.001). There was no adverse reaction occurred during period of observation. Conclusions The rhTPO can significantly increase platelet count, and decrease the amount of blood transfused and the medical cost. The administration of rhTPO is safe and efficient for the treatment of sepsis-associated thrombocytopenia.

The clinical study of rhTPO used for the treatment of sepsis-associated thrombocytopenia

Objective To evaluate the efficacy and safety of rhTPO (recombinant human thromobopoietin) employed for the treatment of sepsis-associated thrombocytopenia. Method There were 47 patients with sepsis-associaiod thrombocytopcnia eligible for the prospective, randomized (random number) and controlled clinical study from January 2009 to November 2009 in ICU of the Tianjin First center Hospital. According to the principle of minimum distribution imbalance index, these patients were randomly divided into the rhTPO group (n = 21) and the IVIG (intravenous immunoglobulin) control group (n = 22). In the rhTPO group, rhTPO was given subcutaneously to patients in a dose of 300 U/kg/d for 2 ～ 8 d, and in the IVIG control group, IVIG was used instead of rhTPO in a dose of 400 mg/kg/d for 5 days. Laboratory tests included blood routine examination, hepatic function, kidney function, coagulation function. The amount of blood products used, bleeding events, the days of ICU and hospital stay, total therapy cost and 28-day mortality were compared between two groups. Results The maximal platelet count in the rhTPO group was significantly higer than that in the contral group (t = 2.21, P =0.032). The mean value of difference between minimal and maximal platelet counts in the rhTPO group was much higher than that in the control group (t =7.40, P ＜0. 001). The average platelet count was no statistical difference between two groups before treatment (t =0. 458, P ＞ 0.05), but the average platelet counts in the rhTPO group were significantly higer than those in the contral group on the second and third day after treatment(t = 2. 166 and t = 2. 132, P =0. 036 and P =0.041. There were no statistical differences in incidence of bleeding, length of ICU stay and mortality between two groups (χ2 =0.720, t =0.91 and χ2 =0.264, P ＞0.05) , but the amounts of plasma and platelet transfusion were significantly less in the rhTPO group than those in the control group (t = 2.038 and t =2.252, P=0.048 and P=0.030) and the medical cost was cut down significantly in rhTPO group (t = 16.93, P ＜ 0.001). There was no adverse reaction occurred during period of observation. Conclusions The rhTPO can significantly increase platelet count, and decrease the amount of blood transfused and the medical cost. The administration of rhTPO is safe and efficient for the treatment of sepsis-associated thrombocytopenia.