Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Rizhao Hospital of Traditional Chinese Medicine, Rizhao, China.
Ann Palliat Med. 2021 Oct;10(10):10170-10184. doi: 10.21037/apm-21-2222. Epub 2021 Sep 14.
Endothelium injury and coagulation dysfunction play an important role in the pathogenesis of sepsis. Soluble thrombomodulin (sTM), tissue plasminogen activator-inhibitor complex (t-PAIC), thrombin-antithrombin complex (TAT) and α2-plasmin inhibitor-plasmin complex (PIC) are biomarkers of endothelium injury and coagulation dysfunction. This study aimed to explore the prognostic values and diagnostic performance for septic shock and sepsis-induced disseminated intravascular coagulation (DIC) of endothelial biomarkers.
We conducted an observational study on patients with sepsis admitted to intensive care unit (ICU) at a teaching hospital from January 2016 to December 2018. Levels of sTM, t-PAIC, TAT and PIC were measured at admission day and day 5-7 after admission and detected by qualitative chemiluminescence enzyme immunoassay performed on HISCL automated analyzers.
A total of 179 septic patients and 125 non-septic ICU controls were enrolled. The level of sTM was higher in septic patients compared to ICU controls (OR =1.093, 95% CI: 1.045-1.151, P<0.001). Moreover, higher levels of sTM and t-PAIC were independent predictors of poor 60-day prognosis for septic patients (HR =1.012, 95% CI: 1.003-1.022, P=0.012; HR =1.014, P=0.009). Level of sTM was also higher in patients with septic shock as revealed by multivariate analysis (OR =1.049, 95% CI: 1.020-1.078, P=0.001), as well as in patients with sepsis-induced DIC (OR =1.109, 95% CI: 1.065-1.158, P<0.001). sTM was considered as a sensitive biomarker for the early prediction of septic shock and sepsis-induced DIC, with AUC up to 0.765 (0.687-0.842) and 0.864 (0.794-0.935) of receiver operating characteristic curve.
Most patients developed coagulopathy which was closely linked to endothelial injury in initial phase of sepsis, which was demonstrated by abnormalities in endothelial biomarkers and their strong association with poor 60-day prognosis and development of septic shock and sepsis-induced DIC.
内皮损伤和凝血功能障碍在脓毒症发病机制中起着重要作用。可溶性血栓调节蛋白（sTM）、组织型纤溶酶原激活物-抑制剂复合物（t-PAIC）、凝血酶-抗凝血酶复合物（TAT）和α2-纤溶酶抑制剂-纤溶酶复合物（PIC）是内皮损伤和凝血功能障碍的生物标志物。本研究旨在探讨内皮生物标志物对脓毒症休克和脓毒症诱导的弥散性血管内凝血（DIC）的预后价值和诊断性能。
我们对 2016 年 1 月至 2018 年 12 月在一所教学医院重症监护病房（ICU）收治的脓毒症患者进行了一项观察性研究。在入院当天和入院后 5-7 天测量 sTM、t-PAIC、TAT 和 PIC 水平，并通过 HISCL 自动化分析仪上进行的定性化学发光酶免疫分析进行检测。
共纳入 179 例脓毒症患者和 125 例非脓毒症 ICU 对照组。与 ICU 对照组相比，脓毒症患者的 sTM 水平更高（OR=1.093，95%CI：1.045-1.151，P<0.001）。此外，较高水平的 sTM 和 t-PAIC 是脓毒症患者 60 天预后不良的独立预测因素（HR=1.012，95%CI：1.003-1.022，P=0.012；HR=1.014，P=0.009）。多因素分析显示，sTM 水平在脓毒症休克患者中也更高（OR=1.049，95%CI：1.020-1.078，P=0.001），在脓毒症诱导的 DIC 患者中也更高（OR=1.109，95%CI：1.065-1.158，P<0.001）。sTM 被认为是脓毒症休克和脓毒症诱导的 DIC 早期预测的敏感生物标志物，其 AUC 高达 0.765（0.687-0.842）和 0.864（0.794-0.935）。
大多数患者在脓毒症的初始阶段就出现了凝血功能障碍，这与内皮损伤密切相关，这表现为内皮生物标志物异常，并且与 60 天预后不良以及脓毒症休克和脓毒症诱导的 DIC 的发展密切相关。
