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A randomized, controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsis

Satoshi Gando1*, Daizoh Saitoh2, Hiroyasu Ishikura3, Masashi Ueyama4, Yasuhiro Otomo5, Shigeto Oda6, Shigeki Kushimoto7, Katsuhisa Tanjoh8, Toshihiko Mayumi9, Toshiaki Ikeda10, Toshiaki Iba11, Yutaka Eguchi12, Kohji Okamoto13, Hiroshi Ogura14, Kazuhide Koseki15, Yuichiro Sakamoto16, Yasuhiro Takayama15, Kunihiro Shirai17, Osamu Takasu18, Yoshiaki Inoue19, Kunihiro Mashiko20, Takaya Tsubota21, Shigeatsu Endo22 and Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) Study Group for the JAAM DIC Antithrombin Trial (JAAMDICAT)

Author Affiliations

1 Division Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, N15W7 Kita-ku, Sapporo 060-8638, Japan

2 Division of Traumatology, National Defense Medical College Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

3 Department of Emergency and Critical Care Medicine, Fukuoka University, 8-19-1 Nanakuma, Fukuoka 814-0180, Japan

4 Department of Traumatology, Critical Care Medicine and Burn Center, Social Insurance Chukyo Hospital, 1-1-10 Sanjo, Nagoya 457-0866, Japan

5 Department of Acute Critical Care and Disaster Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-0034, Japan

6 Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-33, Yayoi-cho, Chiba 263-8522, Japan

7 Division of Emergency Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Miyagi 986-2242, Japan

8 Division of Emergency and Critical Care Medicine, Department of Acute Medicine Nihon, University School of Medicine, 30-1 Oyaguchi Kamimachi, Tokyo 173-8610, Japan

9 Department of Emergency and Critical Care Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Nagoya 466-8550, Japan

10 Department of Critical Care and Emergency Medicine, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Tokyo 193-0998, Japan

11 Department of Emergency Medicine, Juntendo University, 2-1-1 Hongo, Tokyo 113-8431, Japan

12 Critical and Intensive Care Medicine, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan

13 Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Kitakyushu 807-8555, Japan

14 Department of Traumatology and Acute Critical Care Medicine, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka 565-0871, Japan

15 Emergency and Critical Care Medicine, Kawaguchi Municipal Medical Center, 180 Nishiaraijyuku, Kawaguchi 333-0833, Japan

16 Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 840-8502, Japan

17 Department of Emergency and Disaster Medicine, Advanced Critical Care Center, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan

18 Department of Emergency and Critical Care Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan

19 Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu 279-0021, Japan

20 Shock and Trauma Center, Chiba-Hokusoh Hospital, Nippon Medical School, 1715 Kamagari, Chiba 270-1694, Japan

21 Emergency and Critical Care Center, Toho University Omori Medical Center, 5-21-16 Omorinishi, Tokyo 143-8540, Japan

22 Department of Critical Care Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan

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Critical Care 2013, 17:R297  doi:10.1186/cc13163

Published: 16 December 2013



To test the hypothesis that the administration of antithrombin concentrate improves disseminated intravascular coagulation (DIC), resulting in recovery from DIC and better outcomes in patients with sepsis, we conducted a prospective, randomized controlled multicenter trial at 13 critical care centers in tertiary care hospitals.


We enrolled 60 DIC patients with sepsis and antithrombin levels of 50 to 80% in this study. The participating patients were randomly assigned to an antithrombin arm receiving antithrombin at a dose of 30 IU/kg per day for three days or a control arm treated with no intervention. The primary efficacy end point was recovery from DIC on day 3. The analysis was conducted with an intention-to-treat approach. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) scoring system. The systemic inflammatory response syndrome (SIRS) score, platelet count and global markers of coagulation and fibrinolysis were measured on day 0 and day 3.


Antithrombin treatment resulted in significantly decreased DIC scores and better recovery rates from DIC compared with those observed in the control group on day 3. The incidence of minor bleeding complications did not increase, and no major bleeding related to antithrombin treatment was observed. The platelet count significantly increased; however, antithrombin did not influence the sequential organ failure assessment (SOFA) score or markers of coagulation and fibrinolysis on day 3.


Moderate doses of antithrombin improve DIC scores, thereby increasing the recovery rate from DIC without any risk of bleeding in DIC patients with sepsis.

Trial registration

UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000882