Recombinant Human Thrombomodulin in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Chest. 2015 Aug;148(2):436-443. doi: 10.1378/chest.14-2746.


Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) presents as episodes of acute respiratory worsening closely associated with endothelial damage and disordered coagulopathy. Recombinant human soluble thrombomodulin (rhTM) regulates the coagulation pathway mainly by reducing thrombin-mediated clotting and enhancing protein C activation. We investigated the efficacy of rhTM for the treatment of patients with AE-IPF.

Methods: This historical control study comprised 40 patients with AE-IPF. Twenty patients treated with rhTM (0.06 mg/kg/d) for about 6 days (rhTM group) and 20 patients treated without rhTM (control group) were evaluated. The predictors of 3-month mortality (logistic regression model) were evaluated.

Results: There was no difference in baseline characteristics between the control group and the rhTM group. Three-month mortality of the rhTM group and control group was 30.0% and 65.0%, respectively. In univariate analysis, C-reactive protein and rhTM therapy were significant determinants for 3-month survival. In multivariate analysis, rhTM therapy (OR, 0.219; 95% CI, 0.049-0.978; P = 0.047) was an independent significant determinant for 3-month survival.

Conclusions: We found that rhTM therapy improved 3-month survival of AE-IPF. The results observed here warrant further investigation of rhTM in randomized control trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • C-Reactive Protein / metabolism
  • Disease Progression
  • Female
  • Historically Controlled Study
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / mortality
  • Logistic Models
  • Male
  • Middle Aged
  • Prognosis
  • Recombinant Proteins / therapeutic use*
  • Thrombomodulin / therapeutic use*
  • Treatment Outcome


  • Recombinant Proteins
  • THBD protein, human
  • Thrombomodulin
  • C-Reactive Protein