Introduction: Thrombomodulin (TM) is a transmembrane protein on the endothelial cell, which forms a 1:1 complex with thrombin. The complex enhances the cascade from protein C to activated protein C (APC), which inactivates factors VIIIa and Va under the presence of protein S, thereby inhibiting further thrombin formation. On the other hand, the N-terminal lectin-like domain (D1) of recombinant human soluble TM (rhTM) decreases the levels of high-mobility group box-1 protein (HMGB1) and lipopolysaccharide in the plasma in experimental endotoxemia. However, it is not known how rhTM is working in the patients with disseminated intravascular coagulation (DIC) following severe sepsis.

Design: Single-center, historical control study.

Materials and Methods: 65 consecutive patients with severe sepsis and septic shock with DIC that needed a ventilator management were included in this study from Jan. 2006 to May 2009. DIC was diagnosed by using the Japanese Association for Acute Medicine DIC criteria. All patients were treated according to the strategy of Surviving Sepsis Campaign Guideline. Initial 45 patients were not treated with rhTM (control group). Last 20 patients were given rhTM (380U/kg/day) for 6 days after fulfilling the entry criteria showing above (rhTM group). Patients were followed for 28 days after the entry. We measured the platelet number and the levels of CRP and FDP on sequential days. We compared increasing rate of platelet and the reduction rate of CRP and FDP as a base for day 0.

Results: The characteristic was the same in two groups. There was higher survival rate in rhTM group compared to control group (75% vs. 53%, p=0.09 by the log-rank test). There was no difference of the increasing rate of platelet number in two groups. The levels of FDP and CRP in the rhTM group were dramatically decreased in day 3 compared to day0, while there was not the same tendency in control group.

Conclusions: We found that rhTM administration reduced the levels of CRP in the patients with DIC following severe sepsis. Although the treatment of rhTM did not statistically improve the survival rate, it might have a crucial role to modulate inflammatory responses in severe sepsis as well as to control the coagulant cascade in DIC.