title: Antithrombin supplementation and risk of bleeding in patients with sepsis-associated disseminated intravascular coagulation.
abstract: BACKGROUND
  Although antithrombin is commonly used for the treatment of sepsis-associated disseminated intravascular coagulation (DIC) in Japan, the factors influencing the incidence of bleeding complications have not been sufficiently studied. The purpose of this survey was to identify the factors that predict clinically relevant bleeding in patients receiving antithrombin for DIC.
  
  
  METHODS
  We analyzed data from 1026 sepsis-associated DIC patients with a baseline antithrombin activity ≤70% who underwent antithrombin supplementation at two dosages (1500IU/day or 3000IU/day) for three consecutive days. The patients' demographic characteristics, parameters before and after the treatment, and co-administered anticoagulants were analyzed in relation to the bleeding events.
  
  
  RESULTS
  Overall, 55 patients (5.36%) experienced bleeding events (major bleeding: 1.75%). Logistic regression analysis revealed that sustained DIC>7days was significantly associated with bleeding (odds ratio: 2.761, P=0.001). In contrast, the higher dose of antithrombin or the co-administration of recombinant thrombomodulin or heparins were not associated with bleeding events.
  
  
  CONCLUSIONS
  A higher dose of antithrombin or the concomitant use of other anticoagulants were not associated with bleeding events. On the other hand, sustained DIC lasting more than one week was associated with an increased risk of bleeding in patients with sepsis-associated DIC.
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Japan. Electronic address: toshiiba@cf6.so-net.ne.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Iba
authors.affiliation: Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Japan. Electronic address: gando@med.hokudai.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Gando
authors.affiliation: Division of Traumatology, National Defense Medical College Research Institute, National Defense Medical College, Japan. Electronic address: ds0711@ndmc.ac.jp.
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
authors.affiliation: Department of Molecular Laboratory Medicine, Mie University Graduate School of Medicine, Japan. Electronic address: wadahide@clin.medic.mie-u.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University G D'Annunzio of Chieti-Pescara, Italy. Electronic address: mdinisio@unich.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Di Nisio
authors.affiliation: Department of Haematology, Manchester Royal Infirmary, United Kingdom. Electronic address: Jecko.thachil@cmft.nhs.uk.
authors.forename: Jecko
authors.initials: J
authors.lastname: Thachil
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy
chemical_list: D000991:Antithrombins
keywords: Antithrombin; Bleeding; Disseminated intravascular coagulation; Sepsis; Thrombomodulin