Impact of recombinant soluble thrombomodulin (thrombomodulin alfa) on disseminated intravascular coagulation

Thromb Res. 2013 May;131(5):436-43. doi: 10.1016/j.thromres.2013.03.008. Epub 2013 Apr 6.


Introduction: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clinical Trials, Phase III as Topic
  • Disseminated Intravascular Coagulation / blood
  • Disseminated Intravascular Coagulation / drug therapy*
  • Disseminated Intravascular Coagulation / microbiology
  • Humans
  • Product Surveillance, Postmarketing / methods
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / blood
  • Recombinant Proteins / therapeutic use
  • Risk Factors
  • Survival Rate
  • Thrombomodulin / blood
  • Thrombomodulin / therapeutic use*


  • Recombinant Proteins
  • Thrombomodulin