CC BY 4.0 · TH Open 2023; 07(01): e65-e75
DOI: 10.1055/a-2009-9073
Original Article

Sepsis-Associated DIC with Decreased Levels of Antithrombin and Fibrinogen is the Target for Combination Therapy with Thrombomodulin Alfa and Antithrombin

Hideo Wada
1   Department of General Medicine, Mie Prefectural General Medical Center, Mie, Japan
Kazuo Kawasugi
2   Faculty of Medical Technology, Teikyo University, Tokyo, Japan
Goichi Honda
3   Department of Medical Affairs, Asahi Kasei Pharma Corporation, Tokyo, Japan
Noriaki Kawano
4   Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan
Toshimasa Uchiyama
5   Department of Laboratory Medicine, National Hospital Organization Takasaki General Medical Center, Gunma, Japan
Seiji Madoiwa
6   Department of Clinical Laboratory Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan
Naoki Takezako
7   Department of Hematology, Nerima Hikarigaoka Hospital, Tokyo, Japan
Kei Suzuki
8   Emergency and Critical Care Center, Mie University Hospital, Mie, Japan
Yoshinobu Seki
9   Department of Hematology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
Takayuki Ikezoe
10   Department of Hematology, Fukushima Medical University, Fukushima, Japan
Toshiaki Iba
11   Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
Kohji Okamoto
12   Department of Surgery, Center for Gastroenterology and Liver Disease, Kitakyushu City Yahata Hospital, Fukuoka, Japan
› Author Affiliations
Funding This work was supported by Asahi Kasei Pharma Corporation, which funded the analysis and English editing of the manuscript.


Background Disseminated intravascular coagulation (DIC) is not a homogeneous condition, but rather includes heterogeneous conditions, and its pathophysiology and outcome vary considerably depending on the background. Although anticoagulant therapy is expected to be of benefit in the treatment of DIC, previous studies have suggested that the benefits are limited only to a specific subtype.

Objects The purpose of this study was to identify the group that would benefit from combination therapy using thrombomodulin/antithrombin.

Methods The data from 2,839 patients registered in the postmarketing surveillance of thrombomodulin were evaluated. The patients were divided into four groups depending on antithrombin and fibrinogen levels, and the additive effects of antithrombin on thrombomodulin were examined in the groups.

Results The DIC score, Sequential Organ Failure Assessment score, and mortality were significantly higher in the DIC group with low-antithrombin/low-fibrinogen than in the DIC groups without either low antithrombin or low fibrinogen. The survival curve was significantly higher in DIC patients with combination therapy than in patients treated with thrombomodulin monotherapy, but this effect was seen only in patients with infection-based DIC.

Conclusion DIC patients with low-antithrombin/low-fibrinogen risk poor outcomes, but they can be the target of combination therapy with antithrombin and thrombomodulin as long as the DIC is due to infection.

Data Availability Statement

The data that support the findings of this study are available from Asahi Kasei Pharma Corporation, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.

Publication History

Received: 28 September 2022

Accepted: 03 January 2023

Accepted Manuscript online:
10 January 2023

Article published online:
22 February 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (

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