Background 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. Methods 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. Results 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). Conclusions 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.

Association between recombinant human soluble thrombomodulin administration dosages and mortality in patients with sepsis-induced disseminated intravascular coagulation

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2025年10月21日

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Tatsuro Kobayashi,
Ryusei Mikami,
Mineji Hayakawa

摘要

Background

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.

Methods

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.

Results

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).

Conclusions

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.