Efficacy and safety of anticoagulant therapy in patients with sepsis: a meta-analysis of randomized controlled trials.

Summary

Across 18 RCTs (n=8053), anticoagulation reduced 28/30-day all-cause mortality in sepsis (RR 0.92) but increased bleeding (RR 1.32). In sepsis with baseline DIC, anticoagulation improved DIC regression yet did not significantly reduce mortality.

Key Findings

• Overall 28/30-day mortality reduction with anticoagulants vs placebo/no therapy (RR 0.92, 95% CI 0.86–0.98; P=0.02).
• In baseline DIC subgroup, significant improvement in DIC regression (RR 1.62, 95% CI 1.32–2.00) but no significant mortality reduction (RR 0.87, 95% CI 0.62–1.22).
• Bleeding complications increased with anticoagulation (RR 1.32, 95% CI 1.16–1.49).

Clinical Implications

Anticoagulation may be considered in selected sepsis patients with careful bleeding risk assessment and monitoring; DIC-specific strategies should prioritize regression while recognizing uncertain mortality effects.

Limitations

• Heterogeneity in anticoagulant classes, dosing, and sepsis definitions across trials; potential variability in bleeding adjudication.
• Lack of individual patient data limits precision for risk stratification and interaction analyses.

Future Directions

Conduct IPD meta-analyses and biomarker-enriched RCTs to identify patients most likely to benefit while minimizing bleeding; harmonize outcome definitions and anticoagulation protocols.