Regional Citrate Anticoagulation in Acute on Chronic Liver Failure: Methodological Considerations Regarding Safety Assessment

Dear Editor,

We read with great interest the recent article by Bhagat et al. titled “Regional citrate anticoagulation compared with non-heparin in continuous renal replacement therapy among acute on chronic liver failure patients”. This study addresses a clinically important and underexplored topic, and the data from an Indian cohort are a valuable contribution to the existing literature.

The finding of a 4.5-fold higher filter clotting risk with no heparin (hazard ratio 4.54; 95% confidence interval 1.54–13.0; p = 0.006), despite similar baseline chronic liver failure consortium acute-on-chronic liver failure (ACLF) scores, is clinically significant, as repeated circuit loss may compromise the adequacy of renal support in this critically ill population.¹

However, we wish to highlight two methodological considerations that may influence the interpretation of these results.

Firstly, the regional citrate anticoagulation (RCA) group comprised only 21 patients; although no episodes of severe hypocalcemia or citrate toxicity were reported, uncommon but clinically significant adverse events, such as citrate accumulation, may not have been captured with adequate statistical power. Previous studies have shown that citrate accumulation (defined as a total-to-ionized calcium ratio >2.5) can occur in patients with severe liver dysfunction, even with protocolized monitoring.²

Secondly, although post-continuous renal replacement therapy (CRRT) serum lactate levels were comparable between groups, reporting serial trends in lactate levels and total-to-ionized calcium ratios would have provided greater insight into occult citrate accumulation.³ We kindly invite the authors to comment on the frequency of citrate dose adjustments made during therapy and whether serial total-to-ionized calcium ratio trends were prospectively monitored and analyzed.

Prospective multicenter studies with larger sample sizes and rigorous citrate monitoring protocols are needed to validate these findings, better characterize the safety profile of RCA-CRRT, and define optimal anticoagulation strategies in this high-risk ACLF population.