Volume 14 Supplement 1

30th International Symposium on Intensive Care and Emergency Medicine

Open Access

Efficacy of recombinant human soluble thrombomodulin in disseminated intravascular coagulation

  • T Yasuda1,
  • N Kiyonaga1,
  • T Ohryorji1,
  • M Nakahara1,
  • N Okayama1,
  • T Kikuchi1,
  • T Imabayashi1,
  • Y Kakihana1 and
  • Y Kanmura1
Critical Care201014(Suppl 1):P408

https://doi.org/10.1186/cc8640

Published: 1 March 2010

Introduction

Soluble thrombomodulin is a promising therapeutic natural anticoagulant that is comparable with antithrombin, tissue factor pathway inhibitor and activated protein C. Recently, a recombinant human soluble thrombomodulin, composed of the active, extracellular domain of thrombomodulin, has become commercially available for patients with disseminated intravascular coagulation (DIC). However, its effect on adhesion molecule or plasminogen activator inhibitor 1 (PAI-1) in patients with DIC is not clear. To elucidate the possible effect of a soluble thrombomodulin on endothelial cell and neutrophil interaction in DIC, we investigated the efficacy of a recombinant human soluble thrombomodulin against not only soluble fibrin (SF) for the sensitive marker of DIC, but also soluble E-selectin (sES) and PAI-1 in patients with DIC.

Methods

We studied 33 patients with DIC associated with sepsis. DIC was diagnosed according to the diagnostic criteria established by the Japanese Association for Acute Medicine. Seventeen of 33 patients (RTM group) were assigned a recombinant human soluble thrombomodulin for 6 consecutive days. SF, sES, and PAI-1 were measured at day 0 (before treatment), and day 7. DIC resolution rate, clinical course of bleeding symptoms, and survival rates at 90 days were evaluated. Data were subjected to Mann-Whitney U test, Kaplan-Meier method and log-rank test (P < 0.05 being considered statistically significant).

Results

The baseline characteristics at study entry in both groups (17 treated and 16 control) were almost similar. There were no significant differences of the serum values of platelet, FDP, D-dimer and PAI-1 between two groups. However, sES and SF values in the RTM group were significantly decreased from 43.9 ± 31.2 (at day 0) to 29.46 ± 15.08 μg/ml (at day 7) (P = 0.044) and from 44.6 ± 35.5 (at day 0) to 18.5 ± 16.6 μg/ml (at day 7) (P = 0.039), respectively. Also both the DIC score and SOFA score improved significantly. There was no incidence of bleeding-related adverse events up to 7 days after the start of infusion in the RTM group. Survival rates at 90 days were 58.8% (RTM group) vs 25.0% (Control group).

Conclusions

In patients administered with recombinant human soluble thrombomodulin, sES and SF decreased and the DIC score and SOFA score improved significantly. There was no significant difference between the thrombomodulin group and Control group in survival rate, but there was a tendency that the RTM group had higher survival rate in comparison with the Control group.

Authors’ Affiliations

(1)
Kagoshima University Hospital

References

  1. Saito H, et al.: J Thromb Haemost. 2007, 5: 31-41. 10.1111/j.1538-7836.2006.02267.xPubMedView ArticleGoogle Scholar

Copyright

© BioMed Central Ltd. 2010

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