血栓标志物对恶性肿瘤患者术后发生静脉血栓栓塞症的预测价值

The predictive value of thrombus markers for venous thromboembolism in patients with malignant tumors after surgery

目的:探讨血栓标志物对恶性肿瘤患者术后发生静脉血栓栓塞症(VTE)的预测价值。方法:回顾性分析2020年7月至2021年2月河北省沧州中西医结合医院150例恶性肿瘤手术患者(观察组)的临床资料,术后随访4周,其中发生VTE者30例(血栓组),未发生VTE者120例(无栓组)。另选同期健康体检者60名为对照组。采用化学发光免疫定量分析法检测凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α 2抗纤溶酶复合物(PIC)、血栓调节蛋白(TM)、组织型纤溶酶原激活剂抑制剂1复合物(tPAIC);对照组检测1次,观察组术前1 d和术后1 d各检测1次。采用受试者工作特征(ROC)曲线评价血栓标志物对恶性肿瘤患者术后发生VTE的预测价值。 结果:肺癌( χ^(2)=12.53, P=0.014)、年龄≥60岁( χ^(2)=6.66, P=0.036)、体质量指数>30 kg/m 2( χ^(2)=40.53, P<0.001)、肿瘤转移( χ^(2)=5.38, P=0.031)、肿瘤分期Ⅲ~Ⅳ期( χ^(2)=5.83, P=0.023)患者术后VTE发生率较高,差异均有统计学意义。观察组TAT、PIC、TM水平均高于对照组(均 P<0.05)。术前血栓组TAT和TM水平均高于无栓组(均 P<0.05),TM预测VTE的价值较高[最佳临界值10.70 TU/ml,曲线下面积(AUC)0.786,灵敏度73.30%,特异度81.70%],TAT和TM联合检测可提高预测价值(AUC 0.796,灵敏度80.00%,特异度77.50%);术后血栓组TAT、PIC、TM、tPAIC水平均高于无栓组(均 P<0.05),TAT预测VTE的价值较高(最佳临界值16.50 ng/ml,AUC 0.887,灵敏度82.36%,特异度71.65%),TAT、PIC、TM和tPAIC联合检测可提高预测价值(AUC 0.913,灵敏度90.00%,特异度88.60%)。手术前后PIC与TAT水平均呈正相关( r=0.66, P<0.001;r=0.64, P<0.001)。 结论:TM可作为早期预测恶性肿瘤患者术后VTE发生的敏感指标,用于提前预防;TAT可作为预测VTE即将发生的特异指标,用于及时干预。TAT、PIC、TM、tPAIC联合检测对VTE的预测价值更高,同时可选用PIC评估出血风险。

Objective To explore the predictive value of thrombus markers for venous thromboembolism(VTE)in patients with malignant tumors after surgery.Methods The clinical data of 150 patients with malignant tumors after surgery admitted to Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine in Hebei Province from July 2020 to February 2021 were retrospectively analyzed.All 150 patients followed-up for 4 weeks were treated as the observation group,including 30 cases with VTE(the thrombosis group)and 120 cases without VTE(the non-thrombosis group).Another 60 cases undergoing healthy physical examination during the same period were selected as the control group.The chemiluminescence immunoassay was used to detect thrombin-antithrombin complex(TAT),plasmin-α2 plasmin inhibitor complex(PIC),thrombomodulin(TM),tissue-type plasminogen activator inhibitor-1 complex(tPAIC).The control group was tested once,and the observation group was tested on the 1 day before the operation and 1 day after the operation.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of thrombus markers for VTE in patients with malignant tumors after surgery.Results The patients with lung cancer(χ^(2)=12.53,P=0.014),≥60 years old(χ^(2)=6.66,P=0.036),body mass index>30 kg/m2(χ^(2)=40.53,P<0.001),tumor metastasis(χ^(2)=5.38,P=0.031),Ⅲ-Ⅳstage(χ^(2)=5.83,P=0.023)had higher incidence of VTE after the operation,and the difference was statistically significant.The levels of TAT,PIC and TM in the observation group were higher than those in the control group(all P<0.05).The levels of TAT and TM in the thrombosis group were higher than those in the non-thrombosis group before the operation,and the difference was statistically significant(all P<0.05).The value of TM in predicting VTE was high[the best cut-off value was 10.70 TU/ml,area under the curve(AUC)was 0.786,the sensitivity was 73.30%,the specificity was 81.70%],the combination of TAT and TM could improve the predictive value(AUC was 0.796,the sensitivity was 80.00%,the specificity was 77.50%).The levels of TAT,PIC,TM and tPAIC in thrombosis group were all higher than those in the non-thrombosis group after the operation,and the difference was statistically significant(all P<0.05).The value of TAT in predicting VTE was high(the best cut-off value was 16.50 ng/ml,AUC was 0.887,the sensitivity was 82.36%,the specificity was 71.65%),the combination of TAT,PIC,TM and tPAIC could improve the predictive value(AUC was 0.913,the sensitivity was 90.00%,the specificity was 88.60%).The level of PIC was positively correlated with TAT before and after the operation(r=0.66,P<0.001;r=0.64,P<0.001).Conclusions TM can be used as a sensitive indicator in the early prediction of VTE for the patients with malignant tumors and it aims at the prevention;TAT can be used as a specific indicator in predicting the development of VTE and it aims at the intervention in time.The combined detection of TAT,PIC,TM and tPAIC can improve the predictive value of VTE.At the same time,PIC can be used to evaluate the risk of bleeding.