Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. Feb 4, 2016; 5(1): 17-26
Published online Feb 4, 2016. doi: 10.5492/wjccm.v5.i1.17
Antithrombin in the treatment of burn trauma
Areta Kowal-Vern, Bruce A Orkin
Areta Kowal-Vern, Bruce A Orkin, Department of General Surgery, Rush University Medical Center, Chicago, IL 60612, United States
Author contributions: Kowal-Vern A designed the review, acquired the literature and drafted the article; Kowal-Vern A and Orkin BA analysed and interpreted the data and literature, made critical revisions related to important intellectual content of the manuscript, and approved the final version of the article to be published.
Conflict-of-interest statement: None.
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: Areta Kowal-Vern, MD, FCAP, FASCP, CTBS, Assistant Professor, Department of General Surgery, Rush University Medical Center, Professional Building, Suite 1138, 1725 Harrison Street, Chicago, IL 60612, United States. akvern@comcast.net
Telephone: +1-312-9427088 Fax: +1-312-9427081
Received: July 29, 2015
Peer-review started: July 29, 2015
First decision: October 8, 2015
Revised: October 28, 2015
Accepted: November 24, 2015
Article in press: November 25, 2015
Published online: February 4, 2016
Processing time: 178 Days and 10.3 Hours
Abstract

Antithrombin (AT) is a natural anticoagulant with anti-inflammatory properties that has demonstrated value in sepsis, disseminated intravascular coagulation and in burn and inhalation injury. With high doses, AT may decrease blood loss during eschar excision, reducing blood transfusion requirements. There are no human randomized, placebo-controlled studies, which have tested the true benefit of this agent in these conditions. Two main forms of AT are either plasma-derived AT (phAT) and recombinant AT (rhAT). Major ovine studies in burn and smoke inhalation injury have utilized rhAT. There have been no studies which have either translated the basic rhAT research in burn trauma, or determined the tolerance and pharmacokinetics of rhAT concentrate infusions in burn patients. Advantages of rhAT infusions are no risk of blood borne diseases and lower cost. However, the majority of human burn patient studies have been conducted utilizing phAT. Recent Japanese clinical trials have started using phAT in abdominal sepsis successfully. This review examines the properties of both phAT and rhAT, and analyzes studies in which they have been utilized. We believe that it is time to embark on a randomized placebo-controlled multi-center trial to establish the role of AT in both civilian and military patients with burn trauma.

Keywords: Antithrombin; Burn trauma; Burn injury; Inhalation injury; Recombinant antithrombin

Core tip: Based on ovine and rat research, and civilian population studies, antithrombin (AT) therapy with either human plasma-derived AT or recombinant AT (rhAT) may be a valuable adjunct treatment in patients with ≥ 25% total body surface area burn. AT has anticoagulant and anti-inflammatory properties, a positive effect on cardiopulmonary function, and wound healing, with concomitant decreases in pneumonia and mortality. Studies in human volunteers with endotoxemia have shown that rhAT doses as high as 200% and 500% are tolerated safely. With adequate high doses, AT may decrease blood loss during eschar excision, and reduce blood transfusion requirements.