Endothelial markers are associated with disseminated intravascular coagulation progression and clinical outcomes in sepsis

Abstract Progression of disseminated intravascular coagulation (DIC) is associated with poor outcomes in sepsis. Given the central role of endothelial injury in sepsis-associated coagulopathy, we investigated the associations of endothelium-related markers with DIC progression and clinical prognosis. In this prospective study, serum heparan sulfate (HS), hyaluronic acid (HA), syndecan-1 (SDC-1), and angiopoietin-2 (Ang-2) were measured in 324 septic patients. Participants were divided into DIC progression and non-progression groups based on a ≥1-point increase in the DIC score from days 1 to 4, and further stratified into survivors or non-survivors according to the 28-day all-cause mortality. DIC progression occurred in 33.02% of the cohort, and the 28-day all-cause mortality rate was 25.00%. All four biomarkers were significantly elevated in patients with DIC progression. After adjustment for platelet count, albumin, fibrinogen, and septic shock, multivariable logistic regression identified HA, SDC‑1, and Ang‑2 as independent risk factors for DIC progression. The areas under the receiver operating characteristic curve (AUCs) for predicting DIC progression were 0.607 (0.551–0.660) for HS (ng/mL), 0.599 (0.544–0.653) for HA (ng/mL), 0.735 (0.683–0.782) for SDC-1 (ng/mL), and 0.706 (0.653–0.755) for Ang-2 (ng/mL). Multivariable Cox regression demonstrated that SDC‑1 and Ang‑2 were independently associated with 28‑day mortality. Restricted cubic spline analysis revealed a U-shaped association between platelet count and DIC progression, with both low and high levels linked to adverse outcomes. In conclusion, endothelium‑related markers are associated with DIC progression and 28‑day mortality in patients with sepsis, indicating their potential value for clinical risk stratification, though prospective validation remains needed.