Serum IL-6 levels in sepsis predict the development of sepsis-induced disseminated intravascular coagulation

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Disseminated intravascular coagulation (DIC) significantly increases sepsis mortality rates to 40-80%, making early identification crucial for improved outcomes. Interleukin-6 (IL-6) promotes leukocyte activation and immunothrombosis while serving as an early inflammatory marker, suggesting potential utility for predicting DIC development before overt coagulopathy manifests. This single-center observational study analyzed 105 adult sepsis patients admitted to our ICU between October 2022 and July 2024. Serum IL-6 levels were measured on hospital Day 1 using electrochemiluminescence immunoassay. DIC was diagnosed using Japanese Association for Acute Medicine (JAAM) criteria over three days. We employed simple linear regression to assess correlations between log-transformed IL-6 and JAAM-DIC scores, receiver operating characteristic (ROC) analysis to determine optimal cutoff values, and multivariable logistic regression controlling for age, comorbidities, infection site, and Sequential Organ Failure Assessment (SOFA) scores. DIC developed in 75 patients (71.4%). Log IL-6 concentrations were significantly higher in DIC patients (3.70±0.86 vs 3.00±0.82, p=0.001). Correlations between log IL-6 and JAAM-DIC scores strengthened over time (Day 1: p=0.03; Day 3: p=0.0006). ROC analysis identified an optimal cutoff of log IL-6 3.746 (IL-6 = 5,571 pg/mL) with 88.9% specificity and 58.8% sensitivity (AUC=0.715). Among 46 patients exceeding this threshold, 89.1% developed DIC by Day 3, including 75% of those initially without DIC criteria. Multivariable analysis identified log IL-6 (odds ratio [OR] 2.430, 95% confidence interval [CI] 1.327-4.449, p=0.004) and SOFA score (OR 1.224, 95% CI 1.066-1.407, p=0.004) as independent DIC predictors. A combined IL-6/SOFA logistic regression model achieved an area under the curve of 0.773 (95% CI: 0.684-0.861) with 100% specificity at the optimal threshold of 0.810. Log IL-6 alone achieved an AUC of 0.715 with cutoff 3.746, 88.9% specificity, and 58.8% sensitivity, whereas the combined IL-6/SOFA model demonstrated improved discriminatory performance. Early IL-6 elevation independently predicts DIC development with high specificity, identifying high-risk patients before overt coagulopathy. Incorporation of SOFA score substantially enhances DIC prediction accuracy. Day 1 IL-6 >5,571 pg/mL enables earlier reassessment and intervention, potentially improving septic DIC outcomes.

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