The Safety and Efficacy of Regional Citrate Anticoagulation in Therapeutic Plasma Exchange: A Systematic Review and Meta‐Analysis

INTRODUCTION: Regional citrate anticoagulation (RCA) is increasingly utilized for therapeutic plasma exchange (TPE). Currently, many clinical studies have focused on the safety and efficacy of RCA in TPE. However, due to the complex application and the lack of a uniform standard of RCA, the results of these researches, especially citrate-related metabolic complications, varied greatly in different studies. The purpose of this meta-analysis is to assess the safety and efficacy of RCA in TPE. METHODS: We performed a comprehensive search on PubMed, Embase, and the Cochrane Library database from the inception to August 26, 2024. Studies regarding the application of RCA in TPE were included to assess the efficacy and safety of RCA in TPE. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale and the Jadad scale. Meta-analysis was performed using Stata software (version 15.1). RESULTS: There were 13 eligible studies included, involving 4268 RCA-TPE sessions. The pooled rate of extracorporeal circuit clotting, bleeding, citrate accumulation, hypocalcemia, hypernatremia, hypomagnesemia, and metabolic alkalosis was 5.3% (95% CI [2.4-9.2]), 2.0% (95% CI [0.2-5.0]), 1.8% (95% CI [0.0-6.7]), 17.9% (95% CI [2.3-42.5]), 1.7% (95% CI [0.0-5.1]), 45.6% (95% CI [25.9-66.0]), and 14.8% (95% CI [0.5-41.3]), respectively. Subgroup analysis of hypocalcemia and metabolic alkalosis in the membrane therapeutic plasma exchange (mTPE) was 42.1% (95% CI [2.5-89.7]) and 32.4% (95% CI [25.3-39.9]), respectively. Compared to before treatment, the serum sodium and bicarbonate significantly increased, and serum calcium decreased significantly after RCA-TPE treatment. There was no difference in platelet (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), the ratio of total calcium to ionized calcium, total calcium, pH, and base excess (BE) before and after treatment. Subgroup analyses demonstrated that pH and BE in mTPE, and APTT and PT in double filtration plasmapheresis (DFPP) were significantly increased after treatment. CONCLUSION: Regional citrate anticoagulation might be effective in TPE treatments. However, the incidence of hypomagnesemia, hypocalcemia, and metabolic alkalosis is relatively high. Close monitoring and timely adjustment are needed during the process of RCA-TPE treatment to avoid these complications.