Toshiaki Iba

Aims There have been inconsistent reports regarding the effect of antithrombin on sepsis; furthermore, there are limited reports on how dosage affects therapeutic efficacy. Thus, we aimed to perform a systematic review and meta‐analysis of the use of antithrombin for sepsis and a meta‐regression analysis of antithrombin dosage. Methods We included randomized controlled trials (RCTs) and observational studies of adult patients with sepsis who received antithrombin. Outcomes included all‐cause mortality and serious bleeding complications. Statistical analyses and data synthesis were performed using a random‐effects model; further, meta‐regression and funnel plots were used to explore heterogeneity and biases. Results Seven RCTs and six observational studies were included. Most patients in the RCTs and observational studies had severe sepsis and septic‐disseminated intravascular coagulation (DIC), respectively. A meta‐analysis using RCTs showed no significant differences in mortality between the antithrombin and control groups. However, the meta‐analysis of observational studies indicated a trend of decreasing mortality rates with antithrombin administration (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.68–0.92; p = 0.002). Bleeding complications were significantly higher in the antithrombin group than in the control group in both study types (OR, 1.90; 95% CI, 1.52–2.37; p < 0.01). The meta‐regression analysis showed no correlation between antithrombin dosage and mortality. Conclusion A meta‐analysis of RCTs confirmed no survival benefit of antithrombin, whereas that of observational studies, which mostly focused on septic DIC, showed a significant beneficial effect on improving outcomes. Indications of antithrombin should be considered based on its beneficial and harmful effects.