title: Post-marketing surveillance data of thrombomodulin alfa: sub-analysis in patients with sepsis-induced disseminated intravascular coagulation.
abstract: BACKGROUND
  Thrombomodulin alfa (TM-α, recombinant thrombomodulin) significantly improved disseminated intravascular coagulation (DIC) when compared with heparin therapy in a phase III study. Post-marketing surveillance of TM-α was performed to evaluate the effects and safety in patients with sepsis-induced DIC.
  
  
  METHODS
  From May 2008 to April 2010, a total of 1,787 patients with sepsis-induced DIC treated with TM-α were registered. DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) criteria. The DIC resolution and survival rates on day 28 after the last TM-α administration, and changes in DIC, systemic inflammatory response syndrome (SIRS), and sequential organ failure assessment (SOFA) scores and coagulation and inflammation markers were evaluated.
  
  
  RESULTS
  The most frequent underlying disease was infectious focus-unknown sepsis (29.8%). The mean ± SD values of age, dose, and the duration of TM-α administration were 64.7 ± 20.3 years, 297.3 ± 111.4 U/kg/day, and 5.6 ± 3.4 days, respectively. A total of 1,320 subjects (73.9%) received combined administration with other anticoagulants. Both coagulation and inflammation markers, such as fibrin/fibrinogen degradation products, prothrombin time ratio, thrombin-antithrombin complex, and C-reactive protein, as well as JAAM DIC, SIRS, and SOFA scores, significantly and simultaneously decreased after TM-α administration (p < 0.001). DIC resolution and 28-day survival rates were 44.4% and 66.0%, respectively. The 28-day survival rate decreased significantly according to the duration of DIC before TM-α administration (p < 0.001). Total adverse drug reactions (ADRs), bleeding ADRs, and serious bleeding adverse events occurred in 126 (7.1%), 98 (5.5%), and 121 (6.8%) subjects, respectively. On day 28, after the last TM-α administration available for an antibody test, only one patient was positive for anti-TM-α antibodies (0.11%).
  
  
  CONCLUSIONS
  Our results suggest that TM-α is most effective for treating patients with sepsis-induced DIC when administered within the first 3 days after diagnosis.
authors.affiliation: Department of Critical and Intensive Care Medicine, Shiga University of Medical Science, Shiga, Japan ; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin® Injection, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Eguchi
authors.affiliation: Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Gando
authors.affiliation: Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ishikura
authors.affiliation: Division of Traumatology, National Defense Medical College Research Institute, National Defense Medical College, Saitama, Japan.
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
authors.affiliation: Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, School of Medicine, Tochigi, Japan ; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin® Injection, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Mimuro
authors.affiliation: Department of Internal Medicine, Niigata Prefectural Kamo Hospital, Niigata, Japan ; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin® Injection, Tokyo, Japan.
authors.forename: Hoyu
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Laboratory and Molecular Pathology, Graduate School of Medical and Pharmaceutical Science, University of Toyama, Toyama, Japan ; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin® Injection, Tokyo, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kitajima
authors.affiliation: Department of Blood Transfusion, Kyoto Prefectural University of Medicine, Kyoto, Japan ; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin® Injection, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Tsuji
authors.affiliation: Department of Transfusion Medicine, Nagoya University Hospital, Aichi, Japan ; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin® Injection, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: ART Project, Pharmaceuticals Sales Division, Asahi Kasei Pharma Corporation, Tokyo, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Tsujita
authors.affiliation: Post-Marketing Surveillance Dept. Reliability Assurance Center, Asahi Kasei Pharma Corporation, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nagao
authors.affiliation: Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, School of Medicine, Tochigi, Japan ; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin® Injection, Tokyo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata
keywords: Anticoagulant; JAAM criteria; SIRS; SOFA score; Sepsis