Recombinant Human Soluble Thrombomodulin Treatment for Acute Exacerbation of Idiopathic Pulmonary Fibrosis: A Retrospective Study

Abstract

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) can be fatal, and abnormalities in the coagulation system of patients with AE-IPF have been reported. Recombinant human soluble thrombomodulin (rhTM) forms a complex with thrombin to inactivate coagulation. It also inhibits high-mobility group box protein 1 (HMGB-1), which results in the suppression of inflammation. Objectives: We aimed to evaluate the effectiveness of rhTM for the treatment of AE-IPF. Methods: We retrospectively reviewed the medical records of 41 patients with AE-IPF who were admitted to our institution during the period 2006-2013. The clinical features and outcomes of 16 patients treated with rhTM (rhTM group) were compared with those of 25 patients treated with conventional therapy (control group). Patients were treated with corticosteroid (CS) pulse therapy for 3 days, followed by maintenance treatment with a tapered dose of CS. Patients in the rhTM group also received rhTM (0.06 mg/kg/day) for 6 days as an initial treatment, in combination with CS. Results: Except for D-dimer level, there were no significant differences in the baseline characteristics of the 2 groups. When compared with the control group, the rhTM group had a significantly higher survival rate at 3 months (40 vs. 69%, p = 0.048). A univariate Cox proportional hazards regression model showed that the predictive factors for survival were lactate dehydrogenase level and rhTM treatment. Regarding adverse events, 1 patient in the rhTM group developed mild bleeding events. Conclusion: rhTM as an add-on to conventional treatment may improve survival in patients with AE-IPF.

Thrombomodulin for Acute Exacerbations of Idiopathic Pulmonary Fibrosis

“…A total of 11 citations were identified, and after screening, five publications were included in the review [9][10][11][12][13]. All studies were reported from Japan.…”

“…Of enrolled five studies, three were prospective, historical control studies [9,10,13] and two were retrospective studies (11,12). The five studies recruited a total of 77 patients receiving rhTM treatment (rhTM group).…”

“…For rhTM group, the administration of rhTM was started at a dose of 0.06 mg/kg/day once daily for six days, in four of five studies [10][11][12][13]. The treatment with rhTM was followed by continuous intravenous infusion of low-molecular weight heparin (LMWH) (750,000 IU/kg/day) in one study [11].…”

“…As shown in Figure 1, the pooled 1-month mortality was significantly lower in rhTM group (Odds Ratio (OR): 0.25 (95% CI, 0.08-0.77)). Mortality at 3 months was evaluated in four of five studies [9][10][11][12]. It was lower in the rhTM group than in non-rhTM group in all studies.…”

The Influence of Human Soluble Recombinant Thrombomodulin on In-Hospital Mortality in Patients with Acute Respiratory Distress Syndrome and Disseminated Intravascular Coagulation: A Retrospective Multicenter Study

“…In an analysis of acute exacerbation of idiopathic pulmonary fibrosis, Isshiki et al compared outcomes in patients treated with rTM and conventional therapy [10]. That study found that patients treated with rTM had better survival over 90 days.…”