The role of ionized calcium and magnesium in regional citrate anticoagulation and its impact on inflammatory parameters

Introduction: Regional anticoagulation with citrate has been found to be superior to heparin in terms of biocompatibility, and numerous protocols for regional citrate anticoagulation have been published, while a consensus on the target concentration of ionized calcium (Ca2+) in the extracorporeal circuit has not been reached so far. Methods: The aim of this in vitro study was to assess the impact of different citrate concentrations on coagulation as well as on complement activation and cytokine secretion and to investigate the impact of ionized magnesium (Mg2+) on these parameters. Results: We found that citrate effectively reduced coagulation, complement activation, and cytokine secretion in a dose-dependent manner and that a target Ca2+ concentration of 0.2-0.25 mM was required for efficient anticoagulation. Mg2+ triggered complement activation as well as interleukin (IL)-1 beta secretion in lipopolysaccharide (LPS)-stimulated whole blood in a dose-dependent manner and independently of Ca2+. Additionally, it was found to reduce activated clotting time (ACT) in samples with low Ca2+ levels, but not at physiological Ca2+. Conclusions: Taken together, our data support the notion that regional citrate anticoagulation results in decreased release of inflammatory mediators in the extracorporeal circuit, requiring the depletion of both, Ca2+ and Mg2+.