脓毒症性心肌病患者血浆凝血酶-抗凝血酶复合物水平的临床意义

Clinical significance of plasma thrombin-antithrombin complex levels in patients with sepsis-induced cardiomyopathy

目的探讨血浆凝血酶-抗凝血酶复合物(TAT)水平在脓毒症性心肌病患者中的临床意义。方法回顾性分析解放军联勤保障第九〇八医院重症医学科自2020年1月至2022年3月期间收治的107例脓毒症患者,根据入科时心脏超声显示射血分数是否<50%分为普通脓毒症组(n=79)和脓毒症性心肌病组(n=28),比较两组患者入科2 h内的急性生理与慢性健康评分(APACHEⅡ)、乳酸水平、血常规、肝肾功能、心肌钙蛋白I、N末端脑钠肽前体(NT-proBNP)、常规凝血指标和凝血分子标志物[组织型纤溶酶原激活剂-纤溶酶原激活剂抑制剂-1复合物(t-PAIC)、血栓调节蛋白(TM)、TAT、纤溶酶-α2抗纤溶酶复合物(PIC)],用Logistic回归分析脓毒症性心肌病的危险因素,受试者工作特征曲线(ROC)分析危险因素对脓毒症性心肌病的诊断界值,并用Kaplan-Meier法分析低分子肝素抗凝治疗对脓毒症患者28 d生存率的影响。结果与普通脓毒症组入科时的心肌钙蛋白I[0.02(0.01,0.09)ng/ml]、NT-proBNP[1118.09(333.25,2687.00)pg/ml]、乳酸[1.35(0.90,2.60)mmol/L]、TAT[6.50(3.94,12.14)ng/ml]、PIC[1.256(0.668,2.045)μg/ml]及t-PAIC[10.50(6.70,21.30)ng/ml]比较,脓毒症性心肌病组入科时的心肌钙蛋白I[0.75(0.01,6.02)ng/ml]、NT-proBNP[12125.14(4185.89,33611.62)pg/ml]、乳酸[2.35(1.43,4.34)mmol/L]、TAT[19.85(9.08,45.78)ng/ml]、PIC[2.115(0.878,4.114)μg/ml]及t-PAIC[22.03(15.61,33.20)ng/ml]水平均升高(P<0.05)。Logistic回归显示NT-proBNP阳性和TAT水平升高是脓毒症性心肌病发生的独立危险因素。ROC曲线分析显示血浆TAT水平预测脓毒症性心肌病的曲线下面积为0.78;取血浆TAT水平界值为8.26 ng/ml时,其敏感度和特异度依次为0.82和0.63。K-M分析结果显示针对TAT>8.26 ng/ml的脓毒症患者,接受低分子肝素抗凝者28 d生存率是未抗凝者的8.6倍。结论血浆TAT水平升高是脓毒症性心肌病发生的独立危险因素。TAT>8.26 ng/ml的脓毒症患者接受低分子肝素抗凝治疗可能改善预后。

Objective:To investigate the clinical significance of plasma thrombin-antithrombin complex (TAT) levels in patients with sepsis-induced cardiomyopathy(SIC).Methods:One hundred and seven sepsis patients who were admitted to intensive care units (ICU) of the 908th Hospital of Chinese PLA Logistical Support Force were enrolled in the study. Patients were divided into sepsis group ( n=79) and the sepsis-induced cardiomyopathy group ( n=28) according to whether the cardiac ultrasound examination in 2 hours after admission, and the differences of each indicators between the two groups were compared including acute physiological and chronic health score (APACHEⅡ), lactate, blood routine, liver and kidney function, cardiac troponin I, N-terminal?pro-brain?natriuretic?peptide (NT-pro BNP), conventional coagulation tests and molecular markers of coagulation [tissue plasminogen activator-inhibitor complex (t-PAIC), thrombomodulin (TM), TAT, plasmin-α2-plasmin inhibitor complex (PIC)].Logistical?regression?was?used?to analyze the?risk?factors?for sepsis-induced cardiomyopathy and the receiver operating characteristic (ROC) curve was to analyze their cut-off values. The effect of low-molecular-weight heparin anticoagulation therapy on sepsis patients with TAT>8.26 ng/ml was evaluated by Kaplan-Meier analysis. Results:Compared with the cardiac troponin I[0.02(0.01, 0.09) ng/ml], NT-proBNP [1 118.09 (333.25, 2687.00) pg/ml], lactate[1.35(0.90, 2.60) mmol/L], TAT[6.50(3.94, 12.14) ng/ml], PIC[1.256 (0.668, 2.045) μg/ml] and t-PAIC[10.50 (6.70, 21.30) ng/ml] in sepsis group, the cardiac troponin I [0.75(0.01, 6.02) ng/ml], NT-proBNP[12 125.14(4 185.89, 33 611.62) pg/ml], lactate[2.35(1.43, 4.34) mmol/L], TAT[19.85 (9.08, 45.78) ng/ml], PIC[2.115 (0.878, 4.114) μg/ml] and t-PAIC [22.03(15.61,33.20) ng/ml] levels in the sepsis-induced cardiomyopathy group were significantly increased ( P<0.05). Logistical regression showed that positive NT-pro BNP and elevated TAT levels were independent risk factors for sepsis-induced cardiomyopathy. ROC curve analysis showed that the area under the curve of plasma TAT level for predicting sepsis-induced cardiomyopathy was 0.78. The sensitivity and specificity at the cut-off value of plasma TAT level with 8.26 ng/ml were 0.82 and 0.63, respectively. Conclusions:The elevated TAT level was an independent risk factor for the development of sepsis-induced cardiomyopathy. Low-molecular-weight heparin anticoagulation therapy can improve the 28-day survival rate of sepsis patients with TAT>8.26 ng/ml.