Abstract
Disseminated intravascular coagulation is a serious complication of sepsis that leads to severe organ dysfunction and high mortality, thus early and effective treatment is essential. While thrombomodulin alfa is known as an effective therapeutic agent for disseminated intravascular coagulation, its optimal plasma level has yet to be established. The present two-phase investigation was conducted to evaluate the relationship between plasma concentration of thrombomodulin alfa and both therapeutic efficacy and safety in patients with sepsis-induced disseminated intravascular coagulation, in order to clarify the optimal concentration. For the first phase, patients were divided into high- and low-concentration groups based on a plasma trough cutoff level of 600 ng/mL, then treatment efficacy and bleeding-related adverse events were compared. For the second phase, receiver operating characteristic curve analysis was performed to determine the cutoff value for plasma trough concentration that significantly affected clinical outcomes. Treatment efficacy was higher with concentrations ≥600 ng/mL, without an increase in bleeding complications. Furthermore, receiver operating characteristic analysis identified a cutoff value of 1010 ng/mL, with the 90-day survival rate significantly higher at that concentration (91.7% vs. 63.4%, p = 0.017), while safety was maintained. The present findings suggest that for treatment of sepsis-induced disseminated intravascular coagulation, adjustment of thrombomodulin alfa dose to maintain a plasma trough concentration of at least 1010 ng/mL provides an effective and safe therapeutic strategy.