Association between recombinant human soluble thrombomodulin administration dosages and mortality in patients with...

The optimal dosing strategy for recombinant human soluble thrombomodulin (rhTM) in clinical practice for sepsis-induced disseminated intravascular coagulation (DIC) has not been comprehensively evaluated. This study aimed to investigate whether different rhTM dosing strategies influence mortality outcomes in patients with sepsis-induced DIC.

This retrospective, single-center cohort study included hospitalized patients aged ≥ 18 years who were diagnosed with sepsis and received rhTM for DIC treatment between 2011 and 2024. The primary outcome was in-hospital mortality across different rhTM dosing strategies (standard-dose or reduced-dose). The distribution of mortality between the two groups was compared using the log-rank test, and mortality estimates were analyzed using Cox proportional hazards analysis. To address confounding bias, we employed a double robust method that adjusted the model with covariates while accounting for inverse probability weighting of the treatment.

A total of 167 patients were included in the analysis. Of these, 84 patients were in the standard-dose group and 83 patients were in the reduced-dose group. The median rhTM dosage for the entire cohort was 328 U/kg/day, with estimated plasma trough concentrations of 1622 ng/mL and 835 ng/mL in the standard-dose and reduced-dose groups, respectively. The mortality rate was 30% in the standard-dose group and 42% in the reduced-dose group, showing significantly better outcomes (adjusted hazard ratio: 0.561; 95% confidence interval, 0.323-0.973; P = 0.039).

This study demonstrated that a kidney function-based dose reduction strategy for rhTM administration is associated with inferior mortality outcomes in patients with sepsis-induced DIC. Although our findings are limited by the retrospective nature of this study, they provide valuable insights for future verification.