title: The role of ionized calcium and magnesium in regional citrate anticoagulation and its impact on inflammatory parameters.
abstract: BACKGROUND
  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)-1β 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+.
authors.affiliation:  Center for Biomedical Technology, Department for Health Sciences and Biomedicine, Danube University Krems, Krems - Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Strobl
authors.affiliation:  Center for Biomedical Technology, Department for Health Sciences and Biomedicine, Danube University Krems, Krems - Austria.
authors.forename: Stephan
authors.initials: S
authors.lastname: Harm
authors.affiliation:  Center for Biomedical Technology, Department for Health Sciences and Biomedicine, Danube University Krems, Krems - Austria.| Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Department for Health Sciences and Biomedicine, Danube University Krems, Krems - Austria.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Weber
authors.affiliation:  Center for Biomedical Technology, Department for Health Sciences and Biomedicine, Danube University Krems, Krems - Austria.
authors.forename: Jens
authors.initials: J
authors.lastname: Hartmann
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D019343:Citric Acid / Q000494:pharmacology / Q000627:therapeutic use*; D003165:Complement System Proteins; D016207:Cytokines / Q000097:blood; D006801:Humans; D008274:Magnesium / Q000097:blood; D008297:Male; D006435:Renal Dialysis / Q000379:methods*
chemical_list: D000925:Anticoagulants; D016207:Cytokines; D019343:Citric Acid; D003165:Complement System Proteins; D008274:Magnesium; D002118:Calcium