Normalization of Plasma Antithrombin Activity in Patients Requiring Hemodynamic and/or Respiratory Support has Anti-inflammatory Properties Related to Survival

The Italian Antithrombin Sepsis Study has shown that maintenance of antithrombin (AT) levels around 100% results in a 53% reduction in the 30-day mortality risk of intensive care unit patients with sepsis and/or post-surgical complications requiring hemodynamic and/or respiratory support [1, 2]. The changes in a series of coagulation and fibrinolysis parameters were evaluated with the aim of correlating such changes with the potential effect of AT treatment on survival and exploring the predictive value of laboratory tests on 30-day mortality [3]. Blood samples from 119 patients were taken at baseline and then daily until day 7 from the beginning of AT or placebo infusion. The parameters evaluated were: AT activity, protein C (PC) and S activity and antigen levels, α2-antiplasmin and plasminogen activity, fibrin and fibrinogen degradation products, plasmin-antiplasmin complex, prothrombin fragment 1.2, and thrombin-antithrombin (TAT) complex. Prealbumin was also measured to correct for impaired liver synthesis of coagulation and fibrinolysis factors and inhibitors. Improvement — but never normalization — in most of the laboratory parameters was observed over time. In addition to AT, treatment only affected TAT levels (p = 0.05). In a Cox survival regression model, including the presence of septic shock, the multiorgan failure (MOF) score and the type of treatment as covariates, baseline AT levels were an independent predictor of mortality in the entire series of patients (p = 0.003). After 24 h of treatment, TAT levels were negatively associated with survival (p = 0.05). On the last day of treatment, the levels of PC (p = 0.006) and of fibrinogen-degradation products (p = 0.005) were negatively and positively associated with mortality in the 91 survivors [3].