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

Hideo Wada; Kazuo Kawasugi; Goichi Honda; Noriaki Kawano; Toshimasa Uchiyama; Seiji Madoiwa; Naoki Takezako; Kei Suzuki; Yoshinobu Seki; Takayuki Ikezoe; Toshiaki Iba; Kohji Okamoto

doi:10.1055/a-2009-9073

TH Open, Table of Contents

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

¹Department of General Medicine, Mie Prefectural General Medical Center, Mie, Japan

,

Kazuo Kawasugi

²Faculty of Medical Technology, Teikyo University, Tokyo, Japan

,

Goichi Honda

³Department of Medical Affairs, Asahi Kasei Pharma Corporation, Tokyo, Japan

,

Noriaki Kawano

⁴Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan

,

Toshimasa Uchiyama

⁵Department of Laboratory Medicine, National Hospital Organization Takasaki General Medical Center, Gunma, Japan

,

Seiji Madoiwa

⁶Department of Clinical Laboratory Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan

,

Naoki Takezako

⁷Department of Hematology, Nerima Hikarigaoka Hospital, Tokyo, Japan

,

Kei Suzuki

⁸Emergency and Critical Care Center, Mie University Hospital, Mie, Japan

,

Yoshinobu Seki

⁹Department of Hematology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan

,

Takayuki Ikezoe

¹⁰Department of Hematology, Fukushima Medical University, Fukushima, Japan

,

Toshiaki Iba

¹¹Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan

,

Kohji Okamoto

¹²Department of Surgery, Center for Gastroenterology and Liver Disease, Kitakyushu City Yahata Hospital, Fukuoka, Japan

› Author Affiliations

Abstract

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.

Keywords

thrombomodulin - antithrombin - fibrinogen - disseminated intravascular coagulation - sepsis

Full Text

References

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