Decreased antithrombin activity in the early phase of trauma is strongly associated with extravascular leakage, but not with antithrombin consumption: a prospective observational study

BACKGROUND: We conducted a prospective observational study for investigating coagulofibrinolytic changes and mechanisms of antithrombin (AT) alternations in trauma. METHODS: Trauma patients hospitalized for more than seven days were analyzed for coagulofibrinolytic biomarkers. The patients were stratified into two groups according to AT activity level on admission (day 0), comprising normal AT and low AT patients. RESULTS: Thirty-nine patients (median Injury Severity Score 20) exhibited initial coagulatory activation and triphasic fibrinolytic changes. AT activity did not show a negative linear correlation with levels of thrombin-antithrombin complex (TAT), a marker of coagulation activity and AT consumption, but was strongly correlated with levels of albumin (Alb), an index of vascular permeability, on day 0 (r = 0.702, p < 0.001). Furthermore, Alb was one of the independent predictors for AT on day 0. IL-6 on day 0 and thrombomodulin (TM) levels during the study period, reflecting systemic inflammation and endothelial cell injury, respectively, were significantly higher in the lower AT group (n = 10) than in the normal group (n = 29) (IL-6, p = 0.004; TM, p = 0.017). On days 2 and 4, TAT levels in the lower AT group were significantly higher than in the normal group. CONCLUSIONS: Trauma caused clear triphasic coagulofibrinolytic changes. Decreased AT in the later phase might lead to a prolonged hypercoagulation. AT reduction in the initial phase of trauma is strongly associated with extravascular leakage as suggested by the association of Alb depletion with IL-6 and TM elevation, but not with AT consumption.