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

Abstract

Background: The association between antithrombin use and mortality in patients with sepsis-associated disseminated intravascular coagulation (DIC) remains controversial.

Objectives: To examine the hypothesis that antithrombin could be effective in the treatment of patients with sepsis-associated DIC following severe pneumonia.

Methods: Propensity 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.

Results: Severe 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 OR 0.85, 95% CI 0.75-0.97; inverse probability-weighted, adjusted OR 0.85, 95% CI 0.79-0.90). An analysis with the hospital antithrombin-prescribing rate as an instrumental variable showed that receipt of antithrombin was associated with a 9.9% (95% CI 3.5-16.3) reduction in 28-day mortality.

Conclusions: This 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.

Keywords: anticoagulants; antithrombins; outcomes assessment; pneumonia; sepsis.