Bai Huan, Shen Ling, Jing Liang, Liu Weiyong, Sun Ziyong, Tang Ning
Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Corresponding author: Tang Ning, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2022 Jul;34(7):682-688. doi: 10.3760/cma.j.cn121430-20210614-00876.
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.
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 evaluation II (APACHE II) 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 APACHE II score. 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.
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 APACHE II score (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 APACHE II comparing 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 = 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 APACHE II score): OR and 95%CI were 7.675 (4.007-14.702), 5.160 (2.258-11.793)].
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.
探讨凝血酶原时间（PT）对脓毒症患者病情严重程度及预后的预测效能，并与其他常规凝血参数进行比较。
进行回顾性分析。纳入2019年1月1日至12月31日在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例脓毒症患者的临床资料。收集人口统计学和基本临床数据。记录ICU入院时的实验室数据，包括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），并收集ICU入院24小时内的序贯器官衰竭评估（SOFA）评分、急性生理与慢性健康状况评分系统II（APACHE II）评分。此外，还监测了ICU住院期间的一些主要临床事件，如脓毒症休克、弥散性血管内凝血（DIC）等。对预后进行28天的随访观察。根据是否发生脓毒症休克将患者分为脓毒症休克组和非脓毒症休克组，根据28天预后分为生存组和非生存组。比较两组间上述参数的差异。采用Spearman相关方法分析常规凝血参数与SOFA评分或APACHE II评分的相关性。绘制受试者工作特征曲线（ROC曲线）以确定各常规凝血参数对脓毒症休克和28天死亡率的预测效能。根据PT的截断值将脓毒症患者分为两个风险分层，然后比较主要临床和终点结局。应用Kaplan-Meier生存曲线分析基于PT水平不同风险分层的28天累积生存率差异。最后，采用多因素Logistic回归分析探讨延长的PT水平是否为脓毒症休克和28天死亡率的独立危险因素。
302例患者全部纳入，其中脓毒症休克患者120例，非脓毒症休克患者182例。28天内75例患者死亡，227例存活。与非脓毒症休克组或生存组相比，脓毒症休克组或非生存组患者的PT、APTT和TT均较长，D-二聚体、FDP较高，PLT、FIB和AT较低。相关性分析显示，PT和PLT与SOFA评分相关性较好（r值分别为0.503和-0.524，均P<0.01），PT与APACHE II评分相关性较好（r=0.407，P<0.01）。ROC曲线分析显示，PT对脓毒症休克和28天死亡率的预测效能最强。ROC曲线下面积（AUC）及95%置信区间（95%CI）分别为0.831（0.783-0.879）和0.739（0.674-0.805）。截断值分别为16.8 s和16.3 s，敏感性分别为64.2%、72.0%，特异性分别为89.0%、70.9%。基于PT水平的风险分层显示，PT>16.5 s的患者（n=103）与PT≤16.5 s的患者（n=199）相比，28天死亡率、脓毒症休克和DIC发生率以及SOFA和APACHE II评分更高。Kaplan-Meier生存曲线分析显示，PT>16.5 s的患者28天累积生存率显著低于PT≤16.5 s的患者（52.43% vs. 86.93%；Log-Rank检验：χ=49.428，P<0.001）。多因素Logistic回归分析显示，PT>16.5 s是脓毒症休克和28天死亡率的独立危险因素[模型1（纳入SOFA评分）：比值比（OR）及95%CI为6.003（3.040-11.855）、4.842（2.114-11.089）；模型2（纳入APACHE II评分）：OR及95%CI为7.675（4.007-14.702）、5.160（2.258-11.793）]。
与其他常规凝血参数相比，PT对评估脓毒症严重程度及预后具有潜在的最佳预测价值。当患者被诊断为脓毒症且ICU入院时PT结果大于16.5 s时，患者进展为脓毒症休克和短期死亡的风险可能更高。
