Supplementary Material for: Comparison of Anticoagulant Effects of Nafamostat Mesilate and Heparin in Continuous Renal Replacement Therapy for Patients with High Bleeding Risk：A Meta- Analysis Systemic Review

Objectives: To evaluate the effects of Nafamostat versus heparin on anticoagulation efficacy, filter lifespan, bleeding and other adverse events in patients with high bleeding risk undergoing continuous renal replacement therapy. Methods: Computerized retrieval was conducted in PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang, and VIP databases for relevant English or Chinese studies published since their establishment until June 22, 2025. Thirteen studies comparing Nafamostat with heparin for patients with high bleeding risk during continuous renal replacement therapy were included. Two researchers independently performed literature screening, data extraction, and evaluation of literature quality. Meta-analysis was conducted using Stata 18 software. Results: A total of 11 observational studies were included in this research, involving 1,354 patients. The meta-analysis results showed that Nafamostat significantly reduced the risk of bleeding compared to heparin [RR = 0.38, 95% CI (0.20, 0.74), P < 0.05], but there were no statistically significant differences in filter lifespan [SMD = -0.01, 95% CI (-0.50, 0.48), P = 0.053], coagulation events [RR = 0.92, 95% CI (0.33, 2.54), P = 0.868], and mortality [RR = 1.20, 95% CI (0.87, 1.66), P = 0.256]. The subgroup analysis comparing the Nafamostat group to the heparin group showed that NM significantly reduced the risk of bleeding compared to LMWH [RR = 0.20, 95% CI (0.06, 0.71), P = 0.013], while the bleeding risk in the unfractionated heparin group [RR = 0.46, 95% CI (0.20, 0.74), P = 0.071] showed a downward trend but did not reach statistical significance. Patients with platelet counts < 100×10⁹/L [RR = 0.25, 95% CI (0.07, 0.88), P = 0.031] had significantly lower bleeding risk compared to those with platelet counts ≥ 100×10⁹/L [RR = 0.48, 95% CI (0.19, 1.22), P = 0.121]. Conclusion: This systematic review and meta-analysis indicate that in patients with a high risk of bleeding who receive continuous renal replacement therapy (CRRT), Nafamostat has similar anticoagulant efficacy to heparin and can effectively maintain the patency of the extracorporeal circulation tubing. Moreover, Nafamostat significantly reduces the risk of bleeding. Therefore, for CRRT patients with a high risk of bleeding, it is recommended to prioritize the use of Nafamostat as the first-line anticoagulation regimen.