Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis

Author:

Okamoto Takayuki1,Tanigami Hironobu2,Suzuki Koji13,Shimaoka Motomu12ORCID

Affiliation:

1. Department of Molecular Pathobiology and Cell Adhesion Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Japan

2. Department of Anesthesiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan

3. Faculty of Pharmaceutical Science, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka City 513-8679, Japan

Abstract

Deregulated interplay between inflammation and coagulation plays a pivotal role in the pathogenesis of sepsis. Therapeutic approaches that simultaneously target both inflammation and coagulation hold great promise for the treatment of sepsis. Thrombomodulin is an endogenous anticoagulant protein that, in cooperation with protein C and thrombin-activatable fibrinolysis inhibitor, serves to maintain the endothelial microenvironment in an anti-inflammatory and anticoagulant state. A recombinant soluble form of thrombomodulin has been approved to treat patients suffering from disseminated intravascular coagulation (DIC) and has thus far shown greater therapeutic potential than heparin. A phase II clinical trial is currently underway in the USA to study the efficacy of thrombomodulin for the treatment of sepsis with DIC complications. This paper focuses on the critical roles that thrombomodulin plays at the intersection of inflammation and coagulation and proposes the possible existence of interactions with integrins via protein C. Finally, we provide a rationale for the clinical application of thrombomodulin for alleviating sepsis.

Publisher

Hindawi Limited

Subject

Critical Care and Intensive Care Medicine

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