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Thromb Haemost 2016; 115(06): 1157-1166
DOI: 10.1160/TH15-12-0987
Blood Cells, Inflammation and Infection
Schattauer GmbH

Recombinant human soluble thrombomodulin and mortality in sepsis-induced disseminated intravascular coagulation

A multicentre retrospective study
Mineji Hayakawa
1   Emergency and Critical Care Center, Hokkaido University Hospital, Japan
,
Kazuma Yamakawa
2   Department of Emergency and Critical Care, Osaka General Medical Center, Japan
,
Shinjiro Saito
3   Intensive Care Unit, Department of Anesthesiology, Jikei University School of Medicine, Japan
,
Shigehiko Uchino
3   Intensive Care Unit, Department of Anesthesiology, Jikei University School of Medicine, Japan
,
Daisuke Kudo
4   Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Japan
,
Yusuke Iizuka
5   Department of Anesthesiology and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Japan
9   Department of Critical Care, Shonan Kamakura General Hospital, Japan
,
Masamitsu Sanui
5   Department of Anesthesiology and Critical Care Medicine, Jichi Medical University Saitama Medical Center, Japan
,
Kohei Takimoto
6   Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Japan
,
Toshihiko Mayumi
7   Department of Emergency Medicine, University of Occupational and Environmental Health, Japan
,
Kota Ono
8   Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Japan
,
Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study group › Author Affiliations
Further Information

Publication History

Received: 24 December 2015

Accepted after minor revision: 11 February 2016

Publication Date:
27 November 2017 (online)

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Summary

Recombinant human soluble thrombomodulin (rhTM) is a novel class of anticoagulants for treating disseminated intravascular coagulation (DIC). Although rhTM is widely used in clinical settings throughout Japan, there is limited clinical evidence supporting the use of rhTM in patients with sepsis-induced DIC. Furthermore, rhTM is not approved for DIC treatment in other countries. This study aimed to clarify the survival benefits of rhTM administration in critically ill patients. Data from 3,195 consecutive adult patients who were admitted to 42 intensive care units for the treatment of severe sepsis or septic shock between January 2011 and December 2013 were retrospectively analysed, and 1,784 patients were diagnosed with DIC based on the scoring algorithm from the Japanese Association for Acute Medicine DIC (n = 645, rhTM group; n = 1,139, control group). Propensity score matching created 452 matched pairs, and logistic regression analysis revealed a significant association between rhTM administration and lower in-hospital all-cause mortality in the propensity score-matched groups (odds ratio, 0.757; 95 % confidence interval, 0.574–0.999, p = 0.049). Inverse probability of treatment weighted and quintile-stratified analyses also revealed significant associations between rhTM administration and lower in-hospital all-cause mortality. Survival time in the propensity score-matched rhTM group was significantly longer than that in the propensity score-matched control group (hazard ratio, 0.781; 95 % confidence interval, 0.624–0.977, p = 0.03). Bleeding complications were not more frequent in the rhTM groups. In conclusion, this study demonstrated that rhTM administration is associated with reduced in-hospital all-cause mortality among patients with sepsis-induced DIC.

Keywords

Sepsis - disseminated intravascular coagulation - coagulation abnormality - mortality - thrombomodulin

 

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