Identifying dynamic antithrombin Ⅲ trajectories to predict clinical outcomes in intra-abdominal sepsis

Intra-abdominal infection (IAI) is the leading cause of sepsis and is often complicated by disseminated intravascular coagulation (DIC), leading to increased mortality. Antithrombin Ⅲ (AT Ⅲ), a crucial endogenous anticoagulant, becomes significantly depleted during sepsis due to increased consumption and reduced synthesis. Its levels are closely associated with disease severity and clinical outcomes. Currently, there is a lack of evidence on the dynamic changes of AT Ⅲ and their relationship with the severity and prognosis of sepsis caused by IAI.

This was a prospective observational study. The patients with IAI-induced sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of China Medical University between April 20, 2017, and December 31, 2024, constituted the development cohort. Latent class trajectory modeling (LCTM) was applied to classify patients into different subclasses based on the AT Ⅲ level trajectories over the first 7 days after sepsis diagnosis. Clinical characteristics and outcomes were compared among these subclasses. Additionally, the AT Ⅲ trajectory patterns were validated in an external cohort of IAI patients derived from the China Multicenter Sepsis dataset.

Four dynamic AT Ⅲ trajectory subclasses were identified and further validated by data from the development cohort (n=779) and the external validation cohort (n=820): Class 1 exhibited initially low AT Ⅲ levels with a rapid decline during the first 3 days; Class 2 showed initially low AT Ⅲ followed by gradual recovery; Class 3 started with normal AT Ⅲ levels but experienced a sharp decline in the first 3 days; Class 4 maintained AT Ⅲ levels within the normal range throughout. In the development cohort, patients in Class 1 demonstrated the most pronounced coagulation deterioration, characterized by the lowest platelet counts, significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), more severe inflammatory response, and elevated lactate levels, with the highest ICU and 30-day mortality. Moreover, Class 1 consistently showed significantly higher SOFA scores within 7 days after sepsis diagnosis compared to other subgroups. Incorporating the identification of Class 1 dynamic trajectory significantly improved the predictive performance for 30-day mortality (area under the curve = 0.824, P = 0.0015).

This prospective cohort study uncovers heterogeneity in AT Ⅲ trajectories among IAI-induced sepsis, which were closely associated with the disease severity over time. Incorporating Class 1 (initial low AT followed by rapid decline) improves the predictive value for sepsis prognosis.