In the treatment of
disseminated intravascular coagulation (
DIC), which is a complication of underlying diseases such as
infections and malignant
tumors, effective plasma concentrations of
thrombomodulin (TM) alfa range from 300 to 900 ng/mL; however, appropriate concentrations when treating
sepsis-induced
DIC are unknown. Thus, our aim was to determine the relationship between plasma concentrations of TM alfa and its
therapeutic effects, and hemorrhagic adverse events. First, we calculated the plasma trough concentrations of TM alfa in septic
DIC patients. Next, we divided patients into two groups according to their plasma concentrations into a low- and high-concentration group based on a cut-off value of 600 ng/mL. Fourteen and 35 patients were included in the low- and high-concentration groups, respectively. The Japanese Association for Acute Medicine
DIC diagnostic criteria score 4 days after TM alfa administration decreased significantly by 2.06 points from baseline in the high-concentration group compared with 0.71 points in the low-concentration group. The 90-day survival rate was significantly higher in the high-concentration group (85.4%) than in the low-concentration group (49.0%) (hazard ratio, 0.27; 95% confidence interval: 0.09-0.86). In contrast, the incidence of serious
hemorrhage was not significantly different between the groups. The recommended plasma concentration of TM alfa in the treatment of septic
DIC was determined to be higher than 600 ng/mL, and a dose of 380 U/kg (0.06 mg/kg) was necessary to achieve this concentration.