title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Clinical Epidemiology and Health Economics, School of Public Health, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tagami
authors.forename: H
authors.initials: H
authors.lastname: Matsui
authors.forename: H
authors.initials: H
authors.lastname: Horiguchi
authors.forename: K
authors.initials: K
authors.lastname: Fushimi
authors.forename: H
authors.initials: H
authors.lastname: Yasunaga
mesh_terms: D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000737:chemistry*; D000991:Antithrombins / Q000737:chemistry / Q000627:therapeutic use*; D016208:Databases, Factual; D004211:Disseminated Intravascular Coagulation / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D011336:Probability; D012044:Regression Analysis; D012189:Retrospective Studies; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D000991:Antithrombins
keywords: anticoagulants; antithrombins; outcomes assessment; pneumonia; sepsis