血栓弹力图与常用凝血指标相关性及联合检测对晚期肺癌高凝状态评估价值

目的高凝状态是恶性肿瘤预后差的重要因素。血栓弹力图(thrombelastography,TEG)能全面反映凝血因子、血小板功能、纤维蛋白原(fibrinogen,FIB)功能及纤溶过程。本研究通过分析TEG同常规凝血检查(conventional coagulation tests,CCTs)的关系,评估两者在晚期肺癌高凝状态中的诊断效能,探讨合理有效的联合检测方式,为临床发现晚期肺癌高凝状态提供参考。方法选择2018-03-01-2018-09-30青岛阜外心血管病医院内科就诊的Ⅲ^Ⅳ期不可手术晚期肺癌患者72例,以是否合并栓塞分为高凝组(32例)和非高凝组(40例),分别检测血TEG、CCTs、D-二聚体(D-dimer,D-D)和血小板计数(platelet,Plt)。采用Spearman秩次相关分析各观察指标间的关系;通过二元Logistics回归分析筛选关联因素,通过绘制受试者工作特征曲线(receiver operating characteristic curve,ROC)分析诊断效能,ROC曲线下面积(area under the curve,AUC^ROC)比较采用Z检验。结果TEG参数与CCTs指标之间,凝血反应时间(reaction time,R)与活化部分凝血活酶时间(activated partial thromboplastin time,APTT)及D-D相关(rs值均为0.588,均P<0.001);凝血形成时间(K time,K)与血浆凝血酶原时间(plasma prothrombin time,PT)、APTT、FIB及D-D相关(rs值分别为0.283、0.237、0.273和0.335;P值分别为0.016、0.045、0.020和0.004);凝固角(angle)与D-D相关(rs=0.388;P=0.001);最大凝块强度(maxium amplitude,MA)与PT、国际标准化比率(international normalized ratio,INR)、FIB和D-D相关(rs值分别为0.356、0.340、0.345和0.323;P值分别为0.002、0.004、0.003和0.006);凝血综合指数(coagulation composite index,CI)与PT、APTT、INR、FIB及D-D相关(rs值分别为0.257、0.345、0.260、0.270和0.412;P值分别为0.029、0.003、0.028、0.022和<0.001)。Plt、APTT、D-D及R与血栓形成有统计学意义的相关性(rs值分别为0.394、0.529、0.388和0.628,均P<0.001)。TEG各参数之间均有统计学意义的相关性,均P<0.001。Logistics回归分析显示,CCTs参数中APTT、D-D、Plt对回归方程有统计学意义(R^2=0.386,F=14.264,P<0.001);TEG参数中R和MA对回归方程有统计学意义(R^2=0.396,F=22.698,P<0.001);两者联合,PT、R、Plt、APTT、Angel对回归方程有统计学意义(R^2=0.574,F=17.799,P<0.001)。CCTs与TEG的AUC^ROC差异无统计学意义(AUC^ROC差值=0.004,Z=0.070,P=0.945)。联合应用CCTs及TEG的AUC^ROC最高(AUC^ROC=0.966),约登指数为0.838,敏感度为93.75%,特异度为90.00%,与CCTs、TEG的AUC^ROC差异有统计学意义(AUC^ROC差值分别为0.099和0.103;Z值分别为2.750和2.943;P值分别为0.006和0.003)。结论TEG各参数与常规凝血检查有相关性,APTT、Plt、D-D、R和MA是反映高凝状态的主要因素,联合检测CCTs与TEG能更好地反映晚期肺癌患者的凝血功能状态。

Application of thrombelastography and conventional coagulation tests in advanced lung cancer patients to assess hypercoagulability

OBJECTIVE Hypercoagulability is an important factor in poor prognosis of malignant tumors.Thromboelastography(TEG)can fully reflect coagulation factors,platelet function,fibrinogen function and fibrinolysis process.This study aimed to investigate the correlation between TEG and conventional coagulation tests(CCTs)and determine the diagnostic accuracy of TEG and CCTs for hypercoagulability in patients with advanced lung cancer,in order to explore a reasonable and effective joint detection methods to provide a reference for the clinical detection of advanced lung cancer hypercoagulability.METHODS A total of 72 cases with non-surgical advanced lung cancer,stageⅢ-Ⅳwere collected in the Department of Internal Medicine,Qingdao Fuwai Cardiovascular Hospital from March 1st,2018 to September 30th,2018.The patients were divided into hypercoagulation group(32 cases)and non-hypercoagulation group(40 cases)by whether embolization was combined with or not.TEG,CCTs,D-D,Plt were tested.Spearman rank correlation was adopted to analyze the relationships among the observation indexes.Correlation factors were screened by binary Logistics regression analysis,diagnostic efficacy was analyzed by drawing receiver operating characteristic curve(ROC),and Z test was used for comparison of area under the curve(AUCROC).RESULTS Between the parameters of TEG and the indexes of CCTS,the time of coagulation reaction(R)was correlated with activated partial thromboplastin time(APTT)and D-D(rs value was0.588,all P<0.001).The time of coagulation(K)was correlated with plasma prothrombin time(PT),APTT,fibrinogen(FIB)and D-D were correlated(rs values were 0.283,0.237,0.273 and 0.335;P values were 0.016,0.045,0.020and 0.004).Angle was correlated with D-D(rs=0.388,P=0.001).Maximum coagulation intensity(MA)was correlated with PT,international normalized ratio(INR),FIB and D-D(rs values were 0.356,0.340,0.345 and 0.323,P values were0.002,0.004,0.003 and 0.006,respectively).The coagulation composite index(CI)was correlated with PT,APTT,INR,FIB and D-D(rs values were 0.257,0.345,0.260,0.270 and 0.412,P values were 0.029,0.003,0.028,0.022and<0.001,respectively).Plt,APTT,D-D and R were significantly correlated with thrombosis(rs values were 0.394,0.529,0.388 and 0.628,respectively,P<0.001).There were significant correlations among TEG parameters,all P<0.001.Logistic regression analysis showed that APTT,D-D and Plt in CCTs parameters had statistical significance for regression equation(R^2=0.386,F=14.264,P<0.001).R and MA in TEG parameters had statistical significance for regression equation(R^2=0.396,F=22.698,P<0.001).The combination of PT,R,Plt,APTT and Angel had statistical significance for regression equation(R^2=0.574,F=17.799,P<0.001).There was no significant difference in AUCROC between CCTs and TEG(AUCROCdifference=0.004,Z=0.070,P=0.945).AUCROCwith CCTs and TEG was the highest(AUCROC=0.966),Yoden index was 0.838,sensitivity was 93.75%,specificity was 90.00%.There was significant difference between ACROCand CTCs,TEG(AUCROCdifference was 0.099and 0.103,Z value was 2.750 and 2.943,P value was 0.006 and 0.003).CONCLUSIONS The parameters of TEG are correlated with routine coagulation tests.APTT,Plt,D-D,R and MA are the main factors reflecting hypercoagulability.Combined detection of CCTs and TEG can better reflect the coagulation function of patients with advanced lung cancer.