Abstract
Objectives: Patients with sepsis complicated by disseminated intravascular coagulation (septic DIC) have poor outcomes. Thrombomodulin-α (TM-α) is marketed as an anti-DIC drug in Japan. It has been reported that TM-α has also anti-inflammatory effects on sepsis by neutralizing high mobility group box 1 (HMGB1) in basic researches. The aim of this study was to investigate treatment effects of TM-α in patients with septic DIC. Methods: A historical cohort study was performed in a single tertiary emergency center. Patients with septic DIC were classified based on the period of admission. In the TM-α group (n = 30), all patients with septic DIC received TM-α with or without synthetic protease inhibitors (sPI) and/or antithrombin (AT). In the non-TM-α group (n = 23), all patients received sPI and/or AT without TM-α. The primary endpoint was 30-day survival rate. Secondary endpoints included DIC resolution rate at day 7. Results: Demographics, severity of illness, and interventions other than anti-DIC drugs were similar between the groups. The TM-α group had a significantly higher 30-day survival rate compared with the non-TM-α group [90.0% (27/30) vs. 65.2% (15/23), P = 0.041]. In the TM-α and non-TM-α groups, DIC resolution rates were 50.0% (15/30) and 34.8% (8/23) (P = 0.268), respectively. The rate of change in HMGB1 was -48.1% (-66.1 to 97.0) in the TM-α group (n = 7) and 213% (-6.55 to 473) in the non-TM-α group (n = 6) (P = 0.086). The rate of change in interleukin-6 (IL-6) was similar between the groups. Conclusion: TM-α had a positive treatment effect in patients with septic DIC as assessed by 30-day survival rate. The mechanism of this effect may not only be through anti-DIC action, but also an anti-inflammatory effect through reduction of HMGB1
