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
Affiliations
Hideo Wada
Department of General Medicine, Mie Prefectural General Medical Center, Mie, Japan
Kazuo Kawasugi
Faculty of Medical Technology, Teikyo University, Tokyo, Japan
Goichi Honda
Department of Medical Affairs, Asahi Kasei Pharma Corporation, Tokyo, Japan
Noriaki Kawano
Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan
Toshimasa Uchiyama
Department of Laboratory Medicine, National Hospital Organization Takasaki General Medical Center, Gunma, Japan
Seiji Madoiwa
Department of Clinical Laboratory Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan
Naoki Takezako
Department of Hematology, Nerima Hikarigaoka Hospital, Tokyo, Japan
Kei Suzuki
Emergency and Critical Care Center, Mie University Hospital, Mie, Japan
Yoshinobu Seki
Department of Hematology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
Takayuki Ikezoe
Department of Hematology, Fukushima Medical University, Fukushima, Japan
Toshiaki Iba
Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
Kohji Okamoto
Department of Surgery, Center for Gastroenterology and Liver Disease, Kitakyushu City Yahata Hospital, Fukuoka, Japan
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.
