title: Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan.
abstract: Little evidence supports anticoagulant therapy as effective adjuvant therapy to reduce mortality overall in sepsis. However, several studies suggest that anticoagulant therapy may reduce mortality in specific patients. This study aimed to identify a subset of patients with high benefit profiles for anticoagulant therapy against sepsis.
  
  
  
  This post hoc subgroup analysis of a nationwide multicentre retrospective registry was conducted in 42 intensive care units in Japan. Consecutive adult patients with sepsis were included. Treatment effects of anticoagulants, e.g. antithrombin, recombinant thrombomodulin, heparin, and protease inhibitors, were evaluated by stratifying patients according to disseminated intravascular coagulation (DIC) and Sequential Organ Failure Assessment (SOFA) score. Intervention effects of anticoagulant therapy on in-hospital mortality and bleeding complications were analysed using Cox regression analysis stratified by propensity scores.
  
  
  
  Participants comprised 2663 consecutive patients with sepsis; 1247 patients received anticoagulants and 1416 received none. After adjustment for imbalances, anticoagulant administration was significantly associated with reduced mortality only in subsets of patients diagnosed with DIC, whereas similar mortality rates were observed in non-DIC subsets with anticoagulant therapy. Favourable associations between anticoagulant therapy and mortality were observed only in the high-risk subset (SOFA score 13-17; adjusted hazard ratio 0.601; 95 % confidence interval 0.451, 0.800) but not in the subsets of patients with sepsis with low to moderate risk. Although the differences were not statistically significant, there was a consistent tendency towards an increase in bleeding-related transfusions in all SOFA score subsets.
  
  
  
  The analysis of this large database indicates anticoagulant therapy may be associated with a survival benefit in patients with sepsis-induced coagulopathy and/or very severe disease.
  
  
  
  University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012543 ). Registered on 10 December 2013.
authors.affiliation: Department of Emergency and Critical Care, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka, 558-8558, Japan. k.yamakawa0911@gmail.com.|Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan. k.yamakawa0911@gmail.com.
authors.forename: Kazuma
authors.identifier: 0000-0003-2999-4021
authors.initials: K
authors.lastname: Yamakawa
authors.affiliation: Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Umemura
authors.affiliation: Emergency and Critical Care Center, Hokkaido University Hospital, Kita 15 Nishi 7 Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
authors.forename: Mineji
authors.initials: M
authors.lastname: Hayakawa
authors.affiliation: Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kudo
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Jichi Medical University Saitama Medical Center, 1-847 Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Sanui
authors.affiliation: Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Emergency and Critical Care, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka, 558-8558, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yoshikawa
authors.affiliation: Office of Biostatistics and Data Management, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hamasaki
authors.affiliation: Department of Emergency and Critical Care, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka, 558-8558, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujimi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy / Q000401:mortality; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000458:organization & administration; D007564:Japan; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000401:mortality; D063305:Organ Dysfunction Scores; D011379:Prognosis; D057216:Propensity Score; D016016:Proportional Hazards Models; D012042:Registries / Q000706:statistics & numerical data; D012044:Regression Analysis; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy*; D016019:Survival Analysis
chemical_list: D000925:Anticoagulants
keywords: Anticoagulants; DIC; Disseminated intravascular coagulation; Retrospective studies; Sepsis; Subgroup analysis