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朱德妹 张婴元 汪复 郭燕 蒋晓飞 倪语星 孙景勇 应春妹 汪雅萍 王传清 王爱敏 蒋燕群 汤瑾 张泓 李万华 沈燕雅 金文敏 周庭银 陈险峰 张蓓 黄卫春 杨海慧 卫颖珏 汤荣 丁星 吴丽桂 武楠 汪瑞忠 房华 吕新华 朱爱英 《中国感染与化疗杂志》2010,10(6)
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重组人血小板生成素治疗脓毒症血小板减少症 总被引：3，自引：0，他引：3
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. 相似文献
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目的 明确脓毒症血小板表达Toll样受体4(TLR4)变化与血小板活化的关系及对预后的影响.方法 前瞻、对照的临床试验设计.选天津市第一中心医院ICU 2008年5月至2009年12月收治的脓毒症患者64例,除外恶性肿瘤、免疫系统疾病、心肺复苏后、终末期肝或肾功能衰竭及入院24 h内死亡等患者.门诊查体健康志愿者15例为对照组,比较健康对照组和脓毒症组入院时和第3,5,9天外周静脉血血小板计数(PC)及参数(MPV,PDW)、血小板TLR4表达、血小板活化膜糖蛋白GPIⅠb/Ⅲa的PAC-1表达、血浆sCD40L及TNF-α浓度变化及关系;脓毒症组中分为血小板减少症即TCP组(至少1次低于150×109 L-1,27例)和非TCP组(37例),比较两组治疗前后(入院时及入院第9天)TLR4,PAC-1,sCD40L和TNF-α及APACHEⅡ评分、ICU住院时间、出血发生率以及28 d死亡率差异.基于时间测量组间数据比较采用可重复测量的单因素方差分析,两组间参数的比较采用独立样本t检验,计数资料进行x2检验.结果 与健康对照组比较,脓毒症组PC减低(P=0.006),伴随MPV,PDW增大(P=0.046,P＜0.001);血小板FLR4及PAC-1表达同时上调(P＜0.001),且两种受体变化正相关;血浆中sCD40L和TNF-α浓度显著上升(P＜0.001).TCP组PAC-1表达、TNF-α浓度治疗前后均高于非TCP组(P=0.023,P=0.011);治疗后TCP组sCD40L、血小板TLR4表达显著高于非TCP组(P=0.047,P=0.001).TCP组比非TCP组出血发生率高(P=0.024)、ICU住院时间长(P=0.013)、APACHEⅡ评分高(P＜0.01)、28 d病死率高(P=0.048).结论 脓毒症患者血小板TLR4表达上调及伴随的血小板活化与脓毒症血小板减少症发病密切相关,脓毒症并发TCP可能是预后不良标志.Abstract： Objective To unravel the relationship between Toll-like receptor 4 (TLR4) expression in platelets and the activation of platelet in thrombocytopenia (TCP) in case of sepsis. Method A total of 64 patients with sepsis were prospectively studied with control. Platelet count (PC), mean platelet volume (MPV),platelet distribution width (PDW),platelet TLR4 expression, platelet PAC-1 expression, sCD40L and TNF-α concentrations were compared between healthy control group (15 cases) and sepsis group on admission and 3 d,Sd,and 9 days after admission. The changes of MPV and PDW in TCP and non-TCP subgroups of sepsis before and after treatment were recorded. Prognostic index was analyzed. Results The PC was lower in sepsis group (P=0.006), and MPV and PDW were higher in sepsis group than those in healthy control group (P = 0.046, P =0.001). Platelet TLR4 and PAC-1 expressions, and sCD40L and TNF-α levels also increased more significantly in sepsis group (P ＜ 0.001). PAC-1 expression and TNF- level were higher in TCP group than those in non-TCP group before and after treatment (P = 0.023, P = 0.011). The sCD40L concentration and platelet TLR4 expression were significantly higher in treated TCP groups than in non-TCP group (P = 0.047, P = 0.001). Compared with non-TCP,the rate of bleeding was higher (P = 0.024) and the length of ICU stay was longer (P = 0.013).The APACHE Ⅱ score and the 28-day mortality were higher in TCP group (P ＜ 0.01, P = 0.048). Conclusions The elevation of platelet TLR4 expression in sepsis along with platelet activation is closely related to the incidence of thrombocytopenia. The occurrence of TCP is a poor prognosis sign of sepsis. 相似文献
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Objective To explore the correlation between the apheresis platelet transfusion resistance (PTR) and platelet antibody of the patients suffering from hematological diseases (HD). Methods In the light of the corrected count increment(CCI), the effect of platelet transfusion among 207 cases patients who suffered from HD were observed, then the platelet antibody were detected by the use of SEPSA(simplified sensitized erythrocyte platelet serology assay) and counting the occurrence of PTR and positive rate of platelet antibody. The patients were divided into positive platelet antibody group and negative platelet antibody group. The effects of platelet transfusion, 1 hCCI values and 24 hCCI values in two groups were compared. Results The PTR rate was 43.0% and positive rate of platelet antibody was 37.2% The PTR rates in positive platelet antibody group and negative platelet antibody group were absolutely different, which had statistical significance, (P＜ 0. 01).The 1 hCCI and 24 hCCI values in the positive platelet antibody group was obviously lower than those in the negative platelet antibody group, which also had statistical significance, (P＜ 0. 01). Conclusion When the apheresis platelets transfusion is conducted on the HD patients, the platelet antibody detection and platelet typing for positive platelet antibody patients should be made, so as to effectively prevent the occurrence of immune platelet transfusion resistance. 相似文献
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目的 建立一种新的血小板活化释放试验用于监测阿司匹林的治疗反应.方法 采用ARA活化抗凝全血中血小板,应用血细胞分析仪检测MPC的变化.抽取5名健康志愿者外周血标本,取血后迅速混匀,用于MPC、LTAARA和血小板CD62P表达的检测,以优化检测条件,包括ARA活化浓度(分别为0、0.5、1.0、1.5、5.0、10.0 mmol/L)的选择和ARA活化血小板时间的选择(37℃水浴中5、10、20、30、40、50、60、70、80、90 min);评价该方法的稳定性(取血后0、1、2、3 h分别检测)、重复性(MPC、LTAARA、血小板CD62P表达的检测分别重复测定10次,计算批内及批间CV);并通过体外乙酰水杨酸试验验证该方法监测阿司匹林治疗反应的可行性.ARA活化血小板后用CD61-PerCP和CD62P-PE标记,流式细胞仪测定CD62P表达阳性的血小板百分率,对MPC与CD62P的相关性进行分析.选择口服阿司匹林至少7 d的患者为服药组,共93例;选择未口服或停止口服阿司匹林7 d以上的患者为对照组,共100例.用该方法检测服药组与对照组患者ARA(终浓度0.5 mmol/L)活化前后MPC的变化,并与LTAARA方法进行比较,评价该方法的准确性.结果 ARA终浓度为0.5 mmol/L时,血小板活化充分,MPC与血小板膜表面CD62P呈负相关(r=-0.755,P<0.01).37℃水浴活化30 min后MPC达到稳定,取血后室温3 h内MPC保持稳定,新鲜全血MPC的批内CV为1.35%,固定质控全血批间CV为0.71%和0.74%.随着全血中乙酰水杨酸浓度升高(0～6.95 μmol/L),ARA活化血小板后MPC逐渐升高,CD62P逐渐减低,二者呈负相关(r＝-0.765,P<0.01).服药组MPC差值为(8.2±8.6)g/L,MPC变化率为(3.4±3.6)%,对照组分别为(37.4±10.3)g/L、(15.7±4.0)%,差异均有统计学意义(t=21.522、22.409,P均<0.01).MPC变化率ROC曲线下面积为0.992,当临界值为8.7%时,其监测阿司匹林治疗反应的敏感度为96.8%,特异度为99.0%.MPC变化率与LTAARA具有很好的相关性(r=0.720,P<0.01).结论 本研究建立了一种新的监测阿司匹林治疗反应的血小板活化释放试验,可以替代LTAARA用于临床常规检测.Abstract： Objective To establish a new method for monitoring aspirin response by platelet activated-release experiment.Methods The platelets in whole blood were activated by ARA,and the MPC was measured by hematology analyzer.Blood samples were drawn from five healthy volunteers for measuring MPC,LTAARA and platelet membrane CD62P expression.Blood samples were mixed thoroughly right after venipuncture. The concentration of ARA (0,0. 5,1.0,1.5,5.0 and 10. 0 mmol/L) and the time for platelet activation (5,10,20,30,40,50,60,70,80 and 90 min in 37℃ water bathe) were optimized to evaluate the stability (0,1,2 and 3 h after venipuncture) and reproducibility (MPC, LTAARA and platelet membrane CD62p were measured ten times and the CV was calculated). Platelets were mixed with acetylsalicylic acid at different concentrations in vitro in order to verify the validity for monitoring aspirin response. The percentage of CD62p positive platelets after activated by ARA was measured using flow cytometer with CD61-PerCP and CD62p-PE antibodies. The correlation between MPC and CD62P was determined. 100 patients without taking or stop taking aspirin more than 7 days and 93 patients who took aspirin at least 7 days were enrolled. Duplicate measurements of platelet function were performed using the change of MPC (ARA 0. 5 mmol/L) and LTA (ARA 0. 5 mmol/L) among two patient groups to evaluate the accuracy of the new method. Results Platelcts were completely activated by ARA at final concentration of 0. 5 mmol/L. MPC negatively correlated with platelet membrane CD62p(r=-0. 755,P<0. O1 ). MPC was stable for 30 minutes in 37 ℃ water bathe after ARA activation. The result of MPC was consistent at room temperature within 3 hours after blood collection. This method had good reproducibility. CV in batch using fresh whole blood was 1.35% and CV between batches using commercial control whole blood were 0. 71% and 0. 74%. With the concentration of acetylsalicylic acid increased (0-6. 95 μmol/L), MPC increased as CD62P decreased, which showed negative correlation (r=-0. 765 ,P <0. 01 ). The difference of MPC before and after ARA activation (ΔMPC) and MPC variance ratio of the group taking aspirin were ( 8. 2±8. 6) g/L and ( 3.4±3.6) %, and they were (37.4±10. 3 ) g/L and ( 15.7±4.0) % in control group, respectively.ΔMPC and MPC variance ratio showed significant difference between the two groups ( t=21. 522, 22. 409, all P < 0. 01 ). Area under the ROC curve for MPC variance ratio was 0. 992 with sensitivity of 96. 8% and specificity of 99.0% for monitoring the aspirin response using the cut-off of 8. 7%. MPC variance ratio had good correlation with LTAARA (r = 0. 720, P < 0. O1 ). Conclusions A new method for monitoring aspirin response by platelet activated-release experiment is established. It may replace LTAARA for routine clinical examination. 相似文献
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目的 探讨高血压患者血小板活化与炎症反应的改变及其相关性.方法 选择61例原发性高血压患者(高血压组)和64例阵发性室上性心动过速患者(对照组),测定其血清超敏C-反应蛋白(hs-CRP)及平均血小板体积.结果 高血压组患者血清hs-CRP浓度[(3.51±1.95)mg/L]明显高于对照组[(1.15±0.77)mg/L],差异有统计学意义(P＜0.05),平均血小板体积大于对照组[分别为(11.19±2.18)fl与(9.20±2.31)fl],差异有统计学意义(P＜0.05),两者之间呈线性相关(r=0.452,P=0.003).结论 高血压患者存在炎症反应及血小板活化,作为炎症反应及血小板活化的两个观察指标,两者相互作用具有相关性,与高血压的发生发展有密切关系.Abstract： Objective To investigate the changes and correlation between platelet activation and inflammatory response in patients with essential hypertension(EH). Methods Sixty-one patients with essential hypertension and sixty-four patients with paroxysmal supraventricular tachycardia as control group were enrolled in the study. The levels of high sensitivity C reactive protein ( hs-CRP ) and mean platelet volume ( MPV ) were measured and compared between the control group and the essential hypertension group. Results Compared with the control group,the levels of hs-CRP and MPV in the EH group were significantly higher( [3.51 ± 1.95]mg/L vs [ 1.15 ± 0. 77 ] mg/L, P ＜ 0. 05 ). The MPV in the EH group was significantly higher than that in the control group ( [ 11.29 ± 2. 18 ] flvs [ 9. 20 ± 2. 31 ] fl, P ＜ 0. 05 ). The level of hs-CRP positively correlated to the level of M PV (r = 0. 452, P = 0. 003 ). Conlusions There were inflammatory response and platelet activation in patients with EH and the serum levels of hs-CRP and MPV is correlated with the development of essential hypertension. 相似文献
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