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Review
. 2019 May 20;55(5):172.
doi: 10.3390/medicina55050172.

Therapeutic Role of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Takuma Isshiki  1 , Susumu Sakamoto  2 , Sakae Homma  3
Affiliations
Review

Therapeutic Role of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Takuma Isshiki et al. Medicina (Kaunas). .

Abstract

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an acute respiratory worsening of unidentifiable cause that sometimes develops during the clinical course of IPF. Although the incidence of AE-IPF is not high, prognosis is poor. The pathogenesis of AE-IPF is not well understood; however, evidence suggests that coagulation abnormalities and inflammation are involved. Thrombomodulin is a transmembranous glycoprotein found on the cell surface of vascular endothelial cells. Thrombomodulin combines with thrombin, regulates coagulation/fibrinolysis balance, and has a pivotal role in suppressing excess inflammation through its inhibition of high-mobility group box 1 protein and the complement system. Thus, thrombomodulin might be effective in the treatment of AE-IPF, and we and other groups found that recombinant human soluble thrombomodulin improved survival in patients with AE-IPF. This review summarizes the existing evidence and considers the therapeutic role of thrombomodulin in AE-IPF.

Keywords: HMGB-1; acute exacerbation of IPF; coagulation; inflammation; thrombomodulin.

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Conflict of interest statement

The authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Coagulation and fibrinolysis cascade. PC: protein C; aPC: activated protein C; FDP: Fibrin degradation products; PAI-1: plasminogen activator inhibitor 1; t-PA: tissue plasminogen activator.
Figure 2
Figure 2
High-mobility group box-1 (HMGB-1) actions in lungs of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). TLRs: toll-like receptors; RAGE: receptors for advanced glycation end products.
See this image and copyright information in PMC

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