血栓弹力图在新生儿弥散性血管内凝血诊断中的应用价值

Application value of thrombelastography in diagnosis of neonatal disseminated intravascular coagulation

目的探讨血栓弹力图(TEG)在新生儿弥散性血管内凝血(DIC)诊断中的应用价值。方法选择2018年6月至12月于成都市第一人民医院新生儿科确诊新生儿DIC并住院治疗的49例患儿,纳入DIC组(n=49)。选择同期本院临床表现与DIC相似,但不符合新生儿DIC诊断的50例患儿,纳入非DIC组(n=50)。选择同期于本院住院的凝血功能正常的50例新生儿,纳入对照组(n=50)。采取回顾性分析方法,分析3组新生儿的常规凝血功能检测指标,包括凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原水平(FIB)、D二聚体水平,TEG参数,包括凝血反应时间(R值)、凝血形成时间(K值)、凝固角(α角)、血栓最大幅度(MA值),以及血小板计数等凝血功能观察指标。对3组上述指标比较采用方差分析,两两比较采用最小显著性差异(LSD)法。各项凝血功能观察指标与新生儿DIC发生的关系,采用Spearman轶相关分析。各项凝血功能观察指标对新生儿DIC的诊断效能分析,采用受试者工作特征(ROC)曲线法,计算曲线下面积(AUC),并采用约登指数最大原则确定最佳临界值。本研究遵循的程序符合成都市第一人民医院伦理委员会制定的标准,经过该伦理委员会批准(批准文号:2018年KT第009号),并与所有受试者监护人签署临床研究知情同意书。结果①DIC组、非DIC组和对照组患儿PT、APTT、FIB水平、D二聚体水平、R值、K值、α角、MA值和血小板计数总体比较,差异均有统计学意义(F=160.79、40.00、15.30、62.92、431.29、38.19、95.85、54.54、95.60,P<0.001);DIC组患儿的上述各指标分别与非DIC组(LSD-t=4.28、9.17、3.36、35.80、3.48、2.39、12.49、17.48、82.96,P<0.001)和对照组(LSD-t=4.55、19.70、3.55、39.90、6.56、3.20、20.36、19.80、120.07,P<0.001)比较,差异亦均有统计学意义。②PT、APTT、D二聚体水平、R值、K值与新生儿DIC发生呈正相关关系(r=0.513,P<0.001;r=0.321,P<0.001;r=0.561,P<0.001;r=0.608,P<0.001;r=0.237,P=0.018);FIB水平、α角、MA值、血小板计数与新生儿DIC发生呈负相关关系(r=-0.458,P<0.001;r=-0.436,P<0.001;r=-0.431,P<0.001;r=-0.625,P<0.001)。③各项凝血功能观察指标对新生儿DIC的诊断效能分析结果显示,R值诊断新生儿DIC的ROC-AUC最高,为0.919(95%CI:0.874~0.963),根据约登指数最大原则,R值诊断新生儿DIC的最佳临界值为7.5 min,特异度为90.0%,敏感度为67.4%,约登指数为0.705。D二聚体水平诊断新生儿DIC的敏感度最高(85.7%),ROC-AUC为0.892(95%CI:0.836~0.947),其最佳临界值为2 mg/L,特异度为62.0%,约登指数为0.477。结论TEG对新生儿DIC的诊断具有临床价值,可作为常规凝血功能检测的辅助手段,而二者结合则可以更好指导临床对新生儿DIC进行早期诊断和准确治疗.

Objective To investigate the application value of thrombelastography(TEG)in the diagnosis of neonatal disseminated intravascular coagulation(DIC).Methods From June to December 2018,a total of 49 newborns with neonatal DIC in the department of neonatology in Chengdu First People′s Hospital were included in DIC group(n=49).In the same period,a total of 50 non-DIC newborns whose symptoms were similar with DIC were selected as non-DIC group(n=50).Meanwhile,a total of 50 newborns with normal coagulation function in our hospital were selected as control group(n=50).Routine coagulation function detection,including prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen level(FIB),D dimer level,and TEG indexes as coagulation reaction time(R value),coagulation time(K value),coagulation angle(αangle),maximum thrombus amplitude(MA value),as well as platelet count were collected retrospectively and compared using variance analysis among the three groups,and the pairwise comparison was performed using least-significant difference(LSD)method.The relationship between the observation indexes of coagulation function and the occurrence of neonatal DIC was analyzed by Spearman′s correlation analysis.The diagnostic efficiency of each coagulation function observation index for neonatal DIC was determined by the receiver operating characteristic(ROC)curve method.Calculate the area under the curve(AUC),and use the maximum Youden index principle to determine the optimal critical value.The procedures followed in this study were in accordance with the standards established by the Ethics Committee of the Chengdu First People′s Hospital,and this study was approved by this committee(KT No.009 in 2018).Clinical research informed consent was obtained and signed from each individual′s guardian.Results①The total differences of PT,APTT,FIB level,D dimer level,R value,K value,αangle,MA value and platelet count of newborns in the DIC group,non-DIC group and control group were statistically significant(F=160.79,40.00,15.30,62.92,431.29,38.19,95.85,54.54,95.60,P<0.001).The above indicators of newborns in DIC group were respectively compared with those in non-DIC group(LSD-t=4.28,9.17,3.36,35.80,3.48,2.39,12.49,17.48,82.96,P<0.001)and control group(LSD-t=4.55,19.70,3.55,39.90,6.56,3.20,20.36,19.80,120.07,P<0.001),the differences were also statistically significant.②Among the 49 newborns in the DIC group,PT,APTT,D dimer level,R value,K value were positively correlated with the occurrence of neonatal DIC(r=0.513,P<0.001;r=0.321,P<0.01;r=0.561,P<0.001;r=0.608,P<0.001;r=0.237,P=0.018);FIB level,αangle,MA value,platelet count and the occurrence of neonatal DIC were negatively correlated(r=-0.458,P<0.001;r=-0.436,P<0.001;r=-0.431,P<0.001;r=-0.625,P<0.001).③The ROC-AUC of R value for diagnosing neonatal DIC was 0.919(95%CI:0.874-0.963),which was the highest in these observation indexes.According to the principle of maximum Youden index,the best cut-off value of R value was 7.5 min,and the specificity was 90.0%,the sensitivity was 67.4%,and the Youden index was 0.705.The sensitivity of D dimer level for diagnosing neonatal DIC was the highest(85.7%),the ROC-AVC was 0.892(95%CI:0.836-0.947),the best cut-off value was 2 mg/L,specificity was 62.0%,and Youden index was 0.477.Conclusions TEG has clinical value in the diagnosis of neonatal DIC,and can be used as an supplementary means of routine coagulation function detection.The combination of the two methods can better guide clinical early intervention and accurate treatment of neonatal DIC.