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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. May 4, 2015; 4(2): 105-115
Published online May 4, 2015. doi: 10.5492/wjccm.v4.i2.105
Anticoagulant modulation of inflammation in severe sepsis
Karen S Allen, Eva Sawheny, Gary T Kinasewitz
Karen S Allen, Eva Sawheny, Gary T Kinasewitz, Section of Pulmonary and Critical Care, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States
Author contributions: All authors contributed to this manuscript.
Conflict-of-interest: All authors have no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Karen S Allen, MD, Assistant Professor of Medicine, Section of Pulmonary and Critical Care, University of Oklahoma Health Sciences Center, 920 Stanton L Young Blvd WP1310, Oklahoma City, OK 73104, United States. karen-allen@ouhsc.edu
Telephone: +1-405-2716173
Received: October 16, 2014
Peer-review started: October 16, 2014
First decision: December 17, 2014
Revised: January 13, 2015
Accepted: February 4, 2015
Article in press: February 9, 2015
Published online: May 4, 2015
Processing time: 189 Days and 7.3 Hours
Abstract

Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severely ill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis.

Keywords: Inflammation; Protein C; Heparin; Tissue factor pathway inhibitor; Thrombomodulin; Antithrombin; Sepsis; Coagulation; Neutrophil extracellular traps

Core tip: The interaction between the coagulation and inflammatory cascade contributes to the overall pathophysiology of severe sepsis. These processes become unchecked and thus can lead to significant morbidity and mortality. Many anticoagulants have been studied in clinical trials as a means to modulate the inflammatory and coagulation cascade with the aim to improve outcomes for septic patients via modulation of these cascades. This article outlines the pathophysiology and interaction between inflammation and coagulation in severe sepsis and also reviews the anticoagulants previously studied for modulation.