凝血酶原时间对脓毒症患者病情严重程度判断及预后评估的价值研究

Study on the value of prothrombin time for predicting the severity and prognosis of septic patients

目的探讨凝血酶原时间(PT)在脓毒症患者病情严重程度判断及预后评估中的预测价值, 并与其他常规凝血指标比较。方法回顾性纳入2019年1月1日至12月31日华中科技大学同济医学院附属同济医院重症监护病房(ICU)收治的302例脓毒症患者作为研究对象。收集患者人口学及基本临床资料, 入ICU首日PT、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、D-二聚体、纤维蛋白(原)降解产物(FDP)、抗凝血酶(AT)、血小板计数(PLT)等常规凝血指标, 序贯器官衰竭评分(SOFA)、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)等病情评分, 并记录ICU住院期间脓毒性休克、弥散性血管内凝血(DIC)等临床事件发生情况, 观察28 d预后。分别根据是否发生脓毒性休克及28 d预后分组, 比较上述指标在不同组别间的差异。采用Spearman相关法分析常规凝血指标与SOFA评分和APACHEⅡ评分的相关性。绘制受试者工作特征曲线(ROC曲线), 分析常规凝血指标对脓毒性休克及28 d死亡的预测效能, 并进一步根据PT最佳截断值进行危险分层, 比较不同危险分层下主要临床及终点事件的差异;采用Kaplan-Meier生存曲线比较不同危险分层下28 d累积生存率。采用多因素Logistic回归法分析PT延长是否为脓毒性休克及28 d死亡的独立危险因素。结果 302例患者中, 120例发生脓毒性休克, 182例未发生;28 d死亡75例, 存活227例。脓毒性休克组与脓毒症组相比以及死亡组与存活组相比, 均表现为PT、APTT、TT更长, D-二聚体、FDP更高, FIB、AT、PLT更低;相关分析显示, 常规凝血指标中PT、PLT与SOFA评分相关性较好(r值分别为0.503、-0.524, 均P<0.01), PT与APACHEⅡ评分相关性较好(r=0.407, P<0.01)。ROC曲线分析显示, PT对脓毒性休克及28 d死亡均有最佳预测效能, ROC曲线下面积(AUC)及95%可信区间(95%CI)分别为0.831(0.783~0.879)、0.739(0.674~0.805), 最佳截断值分别为16.8 s、16.3 s, 敏感度分别为64.2%、72.0%, 特异度分别为89.0%、70.9%;基于PT水平危险分层显示, 与PT≤16.5 s组(n=199)相比, PT>16.5 s组(n=103)28 d病死率、脓毒性休克和DIC发生率、SOFA及APACHEⅡ评分均更高;Kaplan-Meier生存分析显示, PT>16.5 s组28 d累积生存率显著低于PT≤16.5 s组(52.43%比86.93%;Log-Rank检验:χ^(2)=49.428, P<0.001)。多因素Logistic回归分析显示, PT>16.5 s为脓毒性休克及28 d死亡的独立危险因素〔模型一(纳入SOFA评分):优势比(OR)及95%CI分别为6.003(3.040~11.855)、4.842(2.114~11.089);模型二(纳入APACHEⅡ评分):OR及95%CI分别为7.675(4.007~14.702)、5.160(2.258~11.793)〕。结论与其他常规凝血指标相比, PT对脓毒症患者病情严重程度判断及预后评估均具有潜在的最佳预测价值, 入ICU首日PT>16.5 s的脓毒症患者进展为脓毒性休克及短期死亡的风险更高。

Objective To explore the predictive efficacy of prothrombin time(PT)with regarding for the severity and prognosis of septic patients,along with comparing with other routine coagulation parameters.Methods A retrospective analysis was conducted.The clinical data of 302 septic patients who were admitted to the intensive care unit(ICU)of Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology from January 1 to December 31 in 2019 were enrolled.Demographic and basic clinical data were collected.Laboratory data,including PT,activated partial thromboplastin time(APTT),thrombin time(TT),fibrinogen(FIB),D-dimer,fibrin(fibrinogen)degradation product(FDP),antithrombin(AT),platelet count(PLT)at ICU admission were recorded,and sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluationⅡ(APACHEⅡ)score within 24 hours of admission to ICU were also collected.What's more,some major clinical events,such as septic shock,disseminated intravascular coagulation(DIC),etc.during ICU stay were also monitored.A follow-up 28 days observation of prognosis was performed.The patients were divided into the septic shock group and the non-septic shock group according to the occurrence of septic shock,and they were divided into the survival group and the non-survival group according to the 28-day prognosis.The differences in terms of above parameters between each two groups were compared.Spearman correlation method was used to analyze the correlation between routine coagulation parameters and SOFA score or APACHEⅡscore.Receiver operator characteristic curve(ROC curve)was plotted to determine the predictive efficacy of each routine coagulation parameter with regarding to predict septic shock and 28-day mortality.Based on the cut-off value of PT,the septic patients were divided into two risk stratifications,and then the major clinical and end point outcome were compared.Kaplan-Meier survival curve analysis was applied to investigate the difference of the 28-day cumulated survival rate based on the different risk stratifications of PT level.Finally,multivariate Logistic regression analysis was used to explore whether prolonged PT level was an independent risk factor for septic shock and 28-day mortality.Results The 302 patients were all enrolled,including 120 patients with septic shock and 182 patients without.Seventy-five patients died within 28 days,while 227 survived.Comparing with the non-septic shock group or the survival group,the septic shock group or the non-survival group patients both had longer PT,APTT and TT,higher D-dimer,FDP and lower PLT,FIB and AT.Correlation analysis revealed that PT and PLT were better correlated with SOFA score(r values were 0.503 and-0.524,both P<0.01),and PT was better correlated with APACHEⅡscore(r=0.407,P<0.01).ROC curve analysis showed that PT had the most powerful predictive efficacy for septic shock and 28-day mortality.The area under the ROC curve(AUC)and 95%confidence interval(95%CI)were 0.831(0.783-0.879)and 0.739(0.674-0.805),respectively.The cut-off value were 16.8 s and 16.3 s,respectively,with the sensitivity of 64.2%,72.0%and the specificity of 89.0%,70.9%,respectively.Risk stratification based on PT level revealed that the patients with PT>16.5 s(n=103)had higher rate of 28-day mortality,incidence of septic shock and DIC,and score of SOFA and APACHEⅡcomparing to those with PT≤16.5 s(n=199).Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate was significantly lower in the patients with PT>16.5 s than those with PT≤16.5 s(52.43%vs.86.93%;Log-Rank test:χ^(2)=49.428,P<0.001).Multivariate Logistic regression analysis revealed that PT>16.5 s was an independent risk factor both for septic shock and 28-day mortality[model 1(enrolled SOFA score):odds ratio(OR)and 95%CI were 6.003(3.040-11.855),4.842(2.114-11.089);model 2(enrolled APACHEⅡscore):OR and 95%CI were 7.675(4.007-14.702),5.160(2.258-11.793)].Conclusions Compared with other routine coagulation parameters,PT has the potential best predictive value for evaluating the severity of sepsis and the prognosis.When a patient is diagnosed with sepsis and has a result of PT longer than 16.5 s at ICU admission,the patient may have a higher risk of progression to septic shock and short-term death.