Early Evolution of Sepsis-Associated Coagulopathy and Its Association with Therapeutic Exposures: A Prospective...

Background: Coagulopathy in sepsis represents a dynamic continuum ranging from sepsis-induced coagulopathy (SIC) to disseminated intravascular coagulation (DIC), but its early evolution and clinical determinants remain poorly defined. Objectives: To assess the temporal dynamics of SIC and DIC and examine factors associated with their evolution during the early phases of sepsis. Methods: A prospective longitudinal observational study was conducted on 299 patients with sepsis admitted to the Intermediate Care Unit (IMCU). Patients were evaluated at admission and subsequently at 24, 48, 72, and 96 h, for a total of 1.447 observations. Clinical, laboratory, and hemodynamic data were collected at each time point, and SIC and DIC scores were calculated. The evolution of coagulopathy and its association with clinical and therapeutic variables were analyzed using appropriately adjusted generalized estimating equation (GEE) longitudinal models. Results: The prevalence of SIC increased from 36.8% at baseline to 47.5% at 24 h, and then declined to 20.8% at 96 h. DIC prevalence decreased from 21.7% to 9.7%. Coagulopathy at the previous time point was the main determinant of subsequent coagulopathy (SIC: OR 31.17; DIC: OR 67.17; p < 0.001). Incidence was highest during the early phases (SIC: 12.8% to 2.2%; DIC: 4.7% to 1.1%), whereas persistence decreased over time (SIC: 34.7% to 18.6%; DIC: 18.5% to 8.6%). Higher Sequential Organ Failure Assesment (SOFA) scores were associated with increased risk. Therapeutic anticoagulation was inversely associated with subsequent coagulopathy, including overt DIC positivity among patients without overt DIC at baseline (OR 0.059; 95% CI 0.012-0.290; p < 0.001). Higher cumulative fluid balance was associated with overt DIC in exploratory predicted-probability analyses, independent of vasopressor use, although this gradient did not reach statistical significance in adjusted models and is hypothesis-generating. Diuretic therapy was associated with an increased risk of SIC (OR 2.20; p = 0.008). Conclusions: Coagulopathy in sepsis occurs early and is strongly dependent on its initial trajectory. SIC and DIC represent stages of a continuum, with onset occurring predominantly within the first 24-48 h. The inverse association with therapeutic anticoagulation is hypothesis-generating and should not be interpreted as a treatment effect.