Efficacy of antithrombin administration for patients with sepsis: A systematic review, meta‐analysis, and meta‐regression

• Published in: Acute medicine & surgery Vol. 11; no. 1; pp. e950 - n/a
• Main Authors: Tsuchida, Takumi, Makino, Yuto, Wada, Takeshi, Ushio, Noritaka, Totoki, Takaaki, Fujie, Naoki, Yasuo, Shunsuke, Matsuoka, Tadashi, Koami, Hiroyuki, Yamakawa, Kazuma, Iba, Toshiaki
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2024; John Wiley and Sons Inc; Wiley
• Subjects: Anticoagulants; antithrombin; Bias; bleeding complications; Clinical trials; disseminated intravascular coagulation; Intervention; meta‐analysis; Mortality; Observational studies; Original; Patients; Peritonitis; Sepsis; Systematic review; Thrombosis; Japan; Germany; antithrombin; meta‐analysis; disseminated intravascular coagulation; sepsis; bleeding complications
• ISSN: 2052-8817; 2052-8817
• DOI: 10.1002/ams2.950

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. Antithrombin may benefit septic patients with DIC but not the overall sepsis cohort. Despite potential hemorrhagic risks, considering indications is crucial for balancing benefits and harms. Optimal dosage remains unknown; large‐scale studies are needed to identify the patient population, dosage, administration duration, and target activity levels for effective antithrombin treatment in sepsis.