Association between antithrombin levels and prognosis in patients with sepsis: a retrospective cohort study based on the MIMIC-IV and MIMIC-III databases.

backgroundSepsis is a critical determinant of mortality in critical patients. Antithrombin (AT) plays a pivotal role as a serine protease inhibitor with dual anticoagulant and anti-inflammatory functions, yet its precise role in prognostic stratification remains undefined. This study aimed to investigate the association between AT activity and clinical outcomes in sepsis and to identify critical prognostic thresholds.

methodsWe conducted a retrospective cohort study of 222 septic patients from the MIMIC-IV and MIMIC-III databases. AT activity was measured within the first 24 h following sepsis diagnosis, with the primary outcome defined as 28-day all-cause mortality. For preliminary description, AT activity was categorized into tertiles. The primary analysis utilized restricted cubic splines (RCS) to model the dose-response relationship and identify risk thresholds. Multivariable Cox regression models were employed to adjust for demographics, comorbidities, and SOFA score. Subgroup and survival analyses were performed to evaluate effect modification and visualize outcome differences across threshold-defined risk groups. To visually compare survival outcomes between patient groups defined by the RCS-derived risk thresholds, we generated Kaplan-Meier curves and employed log-rank tests.

resultsA non-linear relationship between AT activity and 28-day mortality was identified, with a marked increase in risk observed below approximately 55% in the overall cohort. Patients with AT activity < 55% had significantly higher 28-day mortality (34.2% vs. 14.4%, p = 0.001), ICU mortality (33.3% vs. 9.0%, p < 0.001), and incidences of disseminated intravascular coagulation (DIC) (22.5% vs. 3.6%, p < 0.001) and acute kidney injury (AKI) (78.4% vs. 62.2%, p = 0.013). Subgroup analysis revealed a significant interaction with hypertension. In the hypertensive subgroup, a similarly elevated risk zone was observed below approximately 64% AT activity. Hypertensive patients below this level had markedly increased 28-day mortality (42.3% vs. 9.62%, p < 0.001), ICU mortality (38.5% vs. 5.77%, p < 0.001), and incidences of DIC (19.2% vs. 1.92%, p < 0.001).

conclusionReduced AT activity was significantly associated with higher mortality and organ dysfunction in sepsis. Risk thresholds were observed at approximately 55% for the overall cohort and 64% among hypertensive patients. Patients below these levels exhibited significantly increased mortality and higher incidences of DIC and AKI. These findings support AT activity as a prognostic biomarker for risk stratification and highlight its potential to inform future management strategies for high-risk patients.