Development of a Unified DIC Scoring System Integrating Endothelial and Hemostatic Molecular Markers for Prognostic Assessment in Sepsis Patients

Background: Diagnosing coagulopathy in sepsis remains challenging, as current Conventional scoring systems based on routine coagulation biomarkers are insufficient to predict mortality accurately. Endothelial molecular markers may improve risk stratification. Objectives: To evaluate the prognostic value of thrombin–antithrombin complex (TAT), tissue-type plasminogen activator–inhibitor complex (t-PAIC), and antithrombin (AT) activity, and to develop a unified score augmenting International Society on Thrombosis and Hemostasis (ISTH) overt-DIC criteria. Methods: In this prospective, longitudinal study, adults with Sepsis-3 presenting to the emergency department underwent serial clinical assessment, routine coagulation testing, and measurement of endothelial markers on Days 1, 3, and 7. Receiver operating characteristic (ROC) analyses screened candidate biomarkers, and multivariable logistic regression identified independent predictors of 28-day mortality. A unified score (Unified ISTH+) was constructed by adding optimal molecular markers to ISTH components and compared with ISTH, JAAM, and SIC criteria. In addition, a non-parametric bootstrap procedure was performed to assess the internal stability and empirical power of the predictive models given the modest sample size. Results: Fifty-four patients (mean age 59.6 ± 16.6 years) were included; 28-day mortality was 31.5%. TAT, t-PAIC, and AT activity were independent predictors of mortality. Individual ROC performance was high for t-PAIC (AUC 0.846), TAT (AUC 0.845), and AT (AUC 0.789). The Unified ISTH+ score achieved superior discrimination (AUC 0.856; 95% CI 0.757–0.955) versus ISTH (0.783), JAAM (0.718), and SIC (0.676), and showed the greatest net benefit on DCA across clinically relevant thresholds. Unified ISTH+-positive patients had higher SOFA/APACHE II scores and worse survival (log-rank p < 0.001). Conclusions: t-PAIC, TAT, and AT activity are strong prognostic markers in sepsis-associated coagulopathy. Incorporating them into a unified ISTH+ score improves mortality prediction versus existing criteria and may enable earlier risk stratification and clinical decision-making.