Efficacy and safety of recombinant human soluble thrombomodulin in patients with sepsis-associated coagulopathy: A systematic review and meta-analysis

Background The efficacy and safety of recombinant human soluble thrombomodulin (rhsTM) have not been definitively proven. The effects may depend on the presence of sepsis-associated coagulopathy (SAC). Objectives The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of rhsTM in patients with SAC defined by high international normalized ratio and low platelet count. Patients/Methods EMBASE, MEDLINE, CENTRAL, and clinicaltrial.gov were searched for randomized controlled trials (RCTs) comparing rhsTM with placebo or no treatment in patients with sepsis. The efficacy outcome was 28-day mortality, and the safety outcome was major bleeding. Results We included 3 RCTs with a total of 1633 patients. Twenty-eight-day mortality was higher in patients with SAC compared with those without SAC (risk ratio [RR] 1.32; 95% confidence intervals [CI], 1.06-1.64). rhsTM was associated with significantly lower 28-day mortality compared with placebo or no treatment in patients with SAC (RR 0.80; 95% CI, 0.65-0.98), but not in those without SAC (RR 1.17; 95% CI, 0.82-1.67) nor in the whole study population (RR 0.88; 95% CI, 0.74-1.04). There was no significant difference in major bleeding between rhsTM and controls in the whole population (RR 1.25; 95% CI, 0.80-1.96), patients with SAC (RR 0.94; 95% CI, 0.45-1.95), and those without SAC (RR 2.26; 95% CI, 0.95-5.35). Conclusions In patients with sepsis, SAC is associated with higher 28-day mortality. The administration of rhsTM reduced 28-day mortality in patients with SAC, but not in those without SAC.