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Open Access Highly Accessed Research

Treatment effects of recombinant human soluble thrombomodulin in patients with severe sepsis: a historical control study

Kazuma Yamakawa12*, Satoshi Fujimi1, Tomoyoshi Mohri1, Hiroki Matsuda1, Yasushi Nakamori1, Tomoya Hirose2, Osamu Tasaki2, Hiroshi Ogura2, Yasuyuki Kuwagata2, Toshimitsu Hamasaki3 and Takeshi Shimazu2

Author Affiliations

1 Department of Emergency and Critical Care, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka 558-8558, Japan

2 Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka Suita, Osaka 565-0871, Japan

3 Department of Biomedical Statistics, Osaka University Graduate School of Medicine, 2-15 Yamadaoka Suita, Osaka 565-0871, Japan

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Critical Care 2011, 15:R123  doi:10.1186/cc10228

Published: 11 May 2011

Abstract

Introduction

Cross-talk between the coagulation system and inflammatory reactions during sepsis causes organ damage followed by multiple organ dysfunction syndrome or even death. Therefore, anticoagulant therapies have been expected to be beneficial in the treatment of severe sepsis. Recombinant human soluble thrombomodulin (rhTM) binds to thrombin to inactivate coagulation, and the thrombin-rhTM complex activates protein C to produce activated protein C. The purpose of this study was to examine the efficacy of rhTM for treating patients with sepsis-induced disseminated intravascular coagulation (DIC).

Methods

This study comprised 65 patients with sepsis-induced DIC who required ventilatory management. All patients fulfilled the criteria of severe sepsis and the International Society on Thrombosis and Haemostasis criteria for overt DIC. The initial 45 patients were treated without rhTM (control group), and the following 20 consecutive patients were treated with rhTM (0.06 mg/kg/day) for six days (rhTM group). The primary outcome measure was 28-day mortality. Stepwise multivariate Cox regression analysis was used to assess which independent variables were associated with mortality. Comparisons of Sequential Organ Failure Assessment (SOFA) score on sequential days between the two groups were analyzed by repeated measures analysis of variance.

Results

Cox regression analysis showed 28-day mortality to be significantly lower in the rhTM group than in the control group (adjusted hazard ratio, 0.303; 95% confidence interval, 0.106 to 0.871; P = 0.027). SOFA score in the rhTM group decreased significantly in comparison with that in the control group (P = 0.028). In the post hoc test, SOFA score decreased rapidly in the rhTM group compared with that in the control group on day 1 (P < 0.05).

Conclusions

We found that rhTM administration may improve organ dysfunction in patients with sepsis-induced DIC. Further clinical investigations are necessary to evaluate the effect of rhTM on the pathophysiology of sepsis-induced DIC.