Optimal Plasma Concentration of Thrombomodulin Alfa to Treat Sepsis-induced Disseminated Intravascular Coagulation

Thrombomodulin alfa (TM alfa) has been shown effective for treatment of disseminated intravascular coagulation (DIC) associated with sepsis, though the optimal therapeutic plasma concentration has not been clarified. In the present study, the plasma trough concentration of TM alfa in septic patients with DIC was determined, then the cutoff value for that concentration showing influence on treatment outcome was calculated using a receiver operating characteristic (ROC) curve. With a cutoff value of 1010, the area under the curve of the ROC was 0.669 (95% CI: 0.530-0.808), with sensitivity of 0.458 and specificity of 0.882. To evaluate its accuracy, patients were divided into those above or below the cutoff value, and 90-day survival rates were compared. The above-cutoff group showed a significantly higher 90-day survival rate (91.7%) as compared to the below-cutoff group (63.4%) (p = 0.017), with a hazard ratio of 0.199 (95% CI: 0.045-0.871). Interestingly, the incidence of hemorrhagic side effects was not significantly different between the groups. Based on these results, the recommended plasma trough concentration of TM alfa for treatment of septic DIC is 1010 ng/mL, which should minimize the risk of severe bleeding while maximizing the therapeutic effect.