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