Effects of combination therapy of Antithrombin and Thrombomodulin for Sepsis-associated Disseminated Intravascular Coagulation: A Systematic Review and Meta-analysis

Background: Disseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although some studies have examined the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) in clinical practice, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review of the combined administration of AT and rTM in treating septic DIC to investigate the usefulness of the combination therapy by random-effects analysis model. Method We searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was serious bleeding complications. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study. Results We analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy(HR 0.67 [0.43–1.05], OR 0.73 [0.45–1.18].)The I 2 values were 60 and 72%, respectively, suggesting high heterogeneity. Trial registration This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: 000049820).