实用医学杂志 ›› 2026, Vol. 42 ›› Issue (18): 3417-3424.doi: 10.3969/j.issn.1006-5725.2026.18.021

• 论著·机制与实践 • 上一篇    

脓毒症患者早期可溶性血栓调节蛋白水平与第5天脓毒症性凝血病的关联

赵宾, 高煜茹, 刘蒙, 苟文钦, 王艺颖, 朱委委, 张东, 宁方玉, 王涛(), 郝东, 王晓芝, 孙婷   

  1. 山东医药大学附属医院重症医学科 (山东 滨州 256603 )
  • 收稿日期:2026-08-17 修回日期:2026-08-31 接受日期:2026-09-01 出版日期:2026-09-25 发布日期:2026-10-19
  • 通讯作者: 王涛
  • 基金资助:
    山东省自然科学基金项目(ZR2024MH116)

Association between early soluble thrombomodulin levels and day-5 sepsis-induced coagulopathy in patients with sepsis

Bin Zhao, Yuru Gao, Meng Liu, Wenqin Gou, Yiying Wang, Weiwei Zhu, Dong Zhang, Fangyu Ning, Tao Wang(), Dong Hao, Xiaozhi Wang, Ting Sun   

  1. Department of Critical Care Medicine,Shandong Medical and Pharmaceutical University Hospital,Binzhou 256603,Shandong,China
  • Received:2026-08-17 Revised:2026-08-31 Accepted:2026-09-01 Online:2026-09-25 Published:2026-10-19
  • Contact: Tao Wang
  • About author:

    Zhao Bin collected and organized the clinical data and wrote the article. Gao Yuru, Liu Meng, Gou Wenqin and Wang Yiying collected and organized the clinical data. Zhu Weiwei, Zhang Dong and Ning Fangyu participated in the statistical analysis. Wang Tao designed the study and performed the final review of the article. Hao Dong, Wang Xiaozhi and Sun Ting revised and reviewed the article. All authors read and approved the final manuscript as submitted.

摘要:

目的 探讨重症监护病房入住第1天(day 1,D1)凝血酶-抗凝血酶复合物(thrombin-antithrombin complex,TAT)、可溶性血栓调节蛋白(soluble thrombomodulin,sTM)、纤溶酶-α₂抗纤溶酶复合物(plasmin-α₂-antiplasmin complex,PIC)及组织型纤溶酶原激活物-纤溶酶原激活物抑制剂-1复合物(tissue plasminogen activator-plasminogen activator inhibitor-1 complex,t-PAIC)与第5天(day 5,D5)脓毒症性凝血病(sepsis-induced coagulopathy,SIC)的关系,并评价sTM的增量区分价值。 方法 基于单中心前瞻性队列开展观察性分析,连续纳入2024年8月至2026年7月入住ICU的成年脓毒症患者。主要分析纳入D1未达SIC标准且D5 SIC状态可评价者,比较两组D1 4项标志物水平及区分能力,并对sTM进行探索性logistic回归和增量区分分析。 结果 共166例纳入主要分析,57例(34.3%)D5达到SIC标准。D5 SIC组4项标志物均较高,Benjamini-Hochberg校正后差异仍有统计学意义。调整SOFA凝血亚评分及APACHE Ⅱ评分后,sTM每升高1个标准差仍与D5 SIC显著相关(OR = 8.93,95%CI:3.91 ~ 20.41,P < 0.001)。4项标志物资料完整的156例中,sTM的AUC最高(0.830)。在163例sTM、PLT和INR资料完整者中,sTM、PLT+INR及PLT+INR+sTM的AUC分别为0.839、0.785和0.888;联合模型高于PLT+INR(P = 0.002)及sTM(P = 0.023)。 结论 D1 sTM升高与D5 SIC显著相关,并显示出较好的单独区分能力;在本研究队列中,将sTM与常规PLT和INR整合后区分度进一步提高。

关键词: 脓毒症, 脓毒症性凝血病, 可溶性血栓调节蛋白, 血小板计数, 国际标准化比值

Abstract:

Objective This study was conducted to investigate the associations between intensive care unit (ICU) day 1 (D1) levels of thrombin-antithrombin complex (TAT), soluble thrombomodulin (sTM), plasmin-α₂-antiplasmin complex (PIC), and tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC) and day 5 (D5) sepsis-induced coagulopathy (SIC), as well as to evaluate the incremental discriminative value of sTM for SIC prediction. Methods This observational analysis was conducted based on a single-center prospective cohort. Consecutive enrollment was performed for adult patients with sepsis admitted to the ICU between August 2024 and July 2026. The primary analysis cohort included patients who did not meet the criteria for SIC on D1 and had evaluable SIC status on D5. We compared D1 levels and discriminative performance of the four candidate biomarkers between patient subgroups, followed by exploratory logistic regression and incremental discrimination analysis focusing on sTM. Results A total of 166 patients were enrolled in this study, among whom 57 (34.3%) met the diagnostic criteria for SIC on D5. The D1 levels of all four biomarkers were significantly higher in the D5 SIC group compared to the non-SIC group, and these differences remained statistically significant after Benjamini-Hochberg multiple testing correction. After adjusting for the SOFA coagulation subscore and APACHE Ⅱ score, each 1-standard-deviation increment in sTM concentration remained independently and significantly associated with D5 SIC (OR = 8.93, 95%CI: 3.91 - 20.41, P < 0.001). Among the 156 patients with complete data for all four biomarkers, sTM yielded the highest area under the receiver operating characteristic curve (AUC) of 0.830. Among the 163 patients with complete data for sTM, PLT, and INR, the AUCs of sTM alone, PLT+INR, and PLT+INR+sTM were 0.839, 0.785, and 0.888, respectively; the AUC of the combined PLT+INR+sTM model was significantly higher than that of PLT+INR (P = 0.002) and sTM alone (P = 0.023). Conclusions Elevated D1 sTM was significantly associated with D5 systemic inflammatory response SIC, and demonstrated good discriminatory performance when used as an independent indicator. In the study cohort analyzed herein, integrating D1 sTM into the routine scoring system based on PLT and INR further improved the discriminatory capacity of the model.

Key words: sepsis, sepsis-induced coagulopathy, soluble thrombomodulin, platelet count, international normalized ratio

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