Antithrombin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study

BackgroundThe association between antithrombin use and mortality in patients with sepsis-associated disseminated intravascular coagulation (DIC) remains controversial. ObjectivesTo examine the hypothesis that antithrombin could be effective in the treatment of patients with sepsis-associated DIC following severe pneumonia. MethodsPropensity score and instrumental variable analyses were performed by use of a nationwide administrative database, the Japanese Diagnosis Procedure Combination inpatient database. The main outcome was 28-day mortality. ResultsSevere pneumonia patients diagnosed with sepsis-associated DIC (n=9075) were categorized into antithrombin (n=2663) and control (n=6412) groups. Propensity score matching created a matched cohort of 2194 pairs of patients with and without antithrombin use. Mortality differences were found between the two groups (antithrombin vs. control: unmatched, 40.8% vs. 45.7%; propensity-matched, 40.6% vs. 44.2%; inverse probability-weighted, 41.1% vs. 45.1%). Multiple logistic regression analyses showed an association between antithrombin use and 28-day mortality (unmatched with propensity score adjusted, adjusted odds ratio [OR]0.87, 95% confidence interval [CI]0.78-0.97; propensity-matched, adjusted OR0.85, 95%CI0.75-0.97; inverse probability-weighted, adjusted OR0.85, 95%CI0.79-0.90). An analysis with the hospital antithrombin-prescribing rate as an instrumental variable showed that receipt of antithrombin was associated with a 9.9% (95%CI3.5-16.3) reduction in 28-day mortality. ConclusionsThis retrospective, large, nationwide database study demonstrates that antithrombin administration may be associated with reduced 28-day mortality in patients with severe pneumonia and sepsis-associated DIC. A large, multinational randomized trial is required.