TorIntroduction As was written in a recent review by Hunt [1], the

TorIntroduction As was written in a recent review by Hunt [1], the fundamental strategy for caring for patients with sepsisassociated disseminated intravascular coagulation (DIC) is the management of underlying infection. During septic DIC, thrombus formation is driven by activated coagulation, the impairment of anticoagulant mechanisms including the antithrombin (AT) system, and compromised fibrin removal arising from the depression of the fibrinolytic system [2]. Microvascular thrombosis contributes to diminished oxygen delivery and subsequent* Correspondence: toshiiba@cf6.so-net.ne.jp 1 Department of Emergency and Disaster Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan Full list of author information is available at the end of the articleorgan dysfunction. Accordingly, anticoagulant therapy is expected to play some role in alleviating this dangerous condition [3]. In the early 2000s, some large-scale randomized controlled trials (RCTs) targeting severe sepsis were conducted [4-6], but none of the anticoagulants that were examined are currently available for clinical use. Actually, sepsis-associated DIC, instead of severe sepsis, might be an appropriate target for these anticoagulant therapies. Indeed, some subgroup analyses of subjects with sepsis-associated DIC in the above-mentioned RCTs have revealed effects on mortality [7,8]. However, the effects of these anticoagulants on septic DIC have not been examined in the well-qualified studies. Recently, a small-sized but properly designed RCT succeeded in demonstrating the efficacy of a physiological dose of AT for? 2014 Iba and Saitoh; licensee BioMed Central. 3-(2,4-Dichlorophenoxy)azetidine This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative bmjopen-2016-011952 Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Iba and Saitoh Journal of Intensive Care (2014)2:Page 2 ofDIC resolution [9]. Following this report, an analysis using a nationwide administrative database in Japan revealed a positive effect of physiological AT use on mortality. Under these circumstances, the ? Harmonized guidance for DIC? has been released by the International Society on Thrombosis and Haemostasis PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/9544797 (ISTH) [10]. 4-Bromopicolinaldehyde In this guidance, AT is graded as ? potentially recommended? . Therefore, our present and future tasks will be to search for appropriate measures for AT use and to accumulate sufficient evidence.ReviewPreclinical evaluationAT is a vitamin K-independent glycoprotein with a molecular weight of approximately 59 kDa and is one of the major natural anticoagulants that have been aggressively studied [8,11,12]. AT inhibits thrombin in a 1:1 fashion and leads to the formation of a thrombin-antithrombin complex (TAT), thereby inactivating the enzymatic activity of thrombin and leading to its elimination from the circulation. Therefore, the inactivation of thrombin is considered to PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/22763976 be a rational therapeutic strategy for DIC. Apart from anticoagulation, the antiinflammatory function of AT can also be explained by the neutralization of thrombin. Thrombin has been implicated in the inflammatory cascade [13]; specifically, it increases leukocyte rolling and adhesion [14] by increasing the e.