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Critical Care Research and Practice
Volume 2012 (2012), Article ID 614545, 10 pages
http://dx.doi.org/10.1155/2012/614545
Review Article

Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis

1Department of Molecular Pathobiology and Cell Adhesion Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Japan
2Department of Anesthesiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan
3Faculty of Pharmaceutical Science, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka City 513-8679, Japan

Received 30 September 2011; Revised 1 December 2011; Accepted 1 December 2011

Academic Editor: Edward A. Abraham

Copyright © 2012 Takayuki Okamoto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.