Effect of combination therapy with recombinant thrombomodulin and antithrombin on outcomes in patients with sepsis-induced disseminated intravascular coagulation in a surgical intensive care unit: a retrospective observational study.

Abstract

Purpose: Sepsis-induced disseminated intravascular coagulation (DIC) is associated with high morbidity and mortality. We evaluated the association of recombinant thrombomodulin (rTM) plus antithrombin (AT) with outcomes in adults with sepsis-induced DIC treated in a surgical intensive care unit (ICU).

Methods: We conducted a single-center retrospective observational study between January 2018 and March 2025. Patients receiving rTM plus AT were compared with those receiving AT alone using 1:1 propensity-score matching. The primary outcome was 28-day all-cause mortality. Secondary outcomes included DIC resolution, ICU length of stay, and severe bleeding requiring transfusion. A predefined subgroup analysis evaluated patients undergoing surgery.

Results: After matching, 45 patient pairs were analyzed. 28-day mortality was 11.1% (5/45) in the rTM + AT group and 15.6% (7/45) in the AT monotherapy group (relative risk, 0.71; 95% confidence interval, 0.24-2.08; log-rank p = 0.53). DIC resolution was more frequent with combination therapy than with AT monotherapy (88.9% vs. 66.7%; p = 0.02), whereas ICU length of stay did not differ significantly. Severe bleeding occurred in 13.3% and 33.3% of patients, respectively (p = 0.04). In the surgical subgroup, 28-day mortality was 6.9% (2/29) vs. 16.0% (4/25; log-rank p = 0.31), while DIC resolution was 93.1% vs. 64.0% (p = 0.02). Severe bleeding occurred in 17.2% and 40.0%, respectively (p = 0.08).

Conclusion: Combination therapy with rTM and AT was associated with a higher rate of DIC resolution and a lower incidence of severe bleeding complications, including among surgical patients. However, no significant difference in 28-day mortality or ICU length of stay was observed.