title: Impact of recombinant soluble thrombomodulin (thrombomodulin alfa) on disseminated intravascular coagulation.
abstract: BACKGROUND
  We assessed the safety and effectiveness of recombinant soluble thrombomodulin (thrombomodulin alfa, TM-α) in the treatment of disseminated intravascular coagulation (DIC) in a post-marketing surveillance.
  
  
  METHODS
  The cases of 3548 patients with DIC caused by infection (n=2516, Infection-DIC) or hematological malignancy (n=1032, Hemat-DIC) were analyzed and compared to the results of a phase III (P-III) study.
  
  
  RESULTS
  The DIC scores were significantly decreased in the Infection-DIC and Hemat-DIC groups with TM-α treatment (both P<0.001). The incidences of critical bleeding adverse drug reactions (ADRs) in the Infection-DIC and Hemat-DIC groups were 2.6% and 2.4%, and the survival rates were 64.1% and 70.7%, respectively. Patients with DIC were subcategorized into three groups (Infection-DIC-1 or Hemat-DIC-1, P-III criteria-matched patients; Infection-DIC-2 or Hemat-DIC-2, P-III criteria-non-matched patients treated solely with TM-α; and Infection-DIC-3 or Hemat-DIC-3, P-III criteria-non-matched patients treated with TM-α and other concomitant anticoagulants). Subcategory analysis revealed that the incidences of critical bleeding ADRs of Hemat-DIC-2 and Hemat-DIC-3 were significantly higher and their survival rates were significantly lower than those of Hemat-DIC-1. By multivariate analysis in Hemat-DIC, younger age (odds ratio: 2.629, P=0.0033) and pre-existing bleeding (odds ratio: 2.044, P=0.019) were found to affect bleeding ADRs and the severity of underlying disease was the most important factor for survival rate (odds ratio: 0.288, P<0.001).
  
  
  CONCLUSIONS
  This surveillance provided real-world data for the safety and effectiveness of TM-α in the treatment of Infection-DIC and Hemat-DIC in general practice settings.
authors.affiliation: The Japanese Society on Thrombosis and Hemostasis Post-marketing Surveillance Committee for Thrombomodulin Alfa, Japan. mimuro-j@jichi.ac.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Mimuro
authors.forename: Hoyu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Isao
authors.initials: I
authors.lastname: Kitajima
authors.forename: Hajime
authors.initials: H
authors.lastname: Tsuji
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Eguchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kuroda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D017326:Clinical Trials, Phase III as Topic; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D011358:Product Surveillance, Postmarketing / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D012307:Risk Factors; D015996:Survival Rate; D018180:Thrombomodulin / Q000097:blood / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D018180:Thrombomodulin