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Dialyse aktuell 2019; 23(02): 70-76
DOI: 10.1055/a-0828-3410
Schwerpunkt | Dialyse
© Georg Thieme Verlag Stuttgart · New York

Zitratbasierte Antikoagulation

Eine Alternative für die intermittierende Dialysetherapie?
Markus Tölle
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Publication Date:
14 March 2019 (online)

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ZUSAMMENFASSUNG

Seit Beginn der Durchführung von extrakorporalen Verfahren stellt sich die Frage nach einer adäquaten Antikoagulation. In Deutschland wird diese im Rahmen der Dialysetherapie überwiegend systemisch mit unfraktionierten oder mit niedermolekularen Heparinen durchgeführt. Es ist zu bedenken, dass viele der Dialysepatienten aufgrund von Komorbiditäten unterschiedliche Antikoagulanzien einnehmen, unter denen bereits das Blutungsrisiko deutlich ansteigt. Darüber hinaus besteht ein breites Nebenwirkungsprofil im Rahmen der Heparintherapie. Eine regionale Antikoagulation ausschließlich im extrakorporalen Kreislauf ohne systemische Beeinflussung des Gerinnungssystems wäre daher wünschenswert. Hier wird die Nutzung von Zitrat im Rahmen kontinuierlicher Nierenersatzverfahren bereits als Standard empfohlen. Im Bereich der intermittierenden Nierenersatzverfahren ist der Stellenwert von Zitrat nicht im gleichen Maße etabliert, was u. a. an der technischen Ausstattung der derzeitigen Dialysemaschinen liegt. Dennoch gibt es verschiedene Möglichkeiten der zitratbasierten regionalen Antikoagulation im extrakorporalen Kreislauf, die in diesem Beitrag zusammenfassend dargestellt werden.

 

  • Literatur

  • 1 Mollison PL. The introduction of citrate as an anticoagulant for transfusion and of glucose as a red cell preservative. Br J Haematol 2000; 108: 13-18
    CrossrefPubMedGoogle Scholar
  • 2 Morgagni G.. Opera Omnia 1764
  • 3 Bright R.. Reports of medical cases. London: 1827
    Google Scholar
  • 4 Mohri H, Fujimura Y, Shima M. et al. Structure of the von Willebrand factor domain interacting with glycoprotein Ib. J Biol Chem 1988; 263: 17901-17904
    CrossrefPubMedGoogle Scholar
  • 5 Remuzzi G, Cavenaghi AE, Mecca G. et al. Prostacyclin-like activity and bleeding in renal failure. Lancet 1977; 2: 1195-1197
    PubMedGoogle Scholar
  • 6 Weigert AL, Schafer AI. Uremic bleeding: pathogenesis and therapy. Am J Med Sci 1998; 316: 94-104
    PubMedGoogle Scholar
  • 7 Holden RM, Harman GJ, Wang M. et al. Major Bleeding in Hemodialysis Patients. Clin J Am Soc Nephrol 2008; 3: 105-110 doi:10.2215/CJN.01810407
    CrossrefPubMedGoogle Scholar
  • 8 Carrier M, Rodger MA, Fergusson D. et al. Increased mortality in hemodialysis patients having specific antibodies to the platelet factor 4-heparin complex. Kidney Int 2008; 73: 213-219 doi:10.1038/sj.ki.5002631
    CrossrefPubMedGoogle Scholar
  • 9 Pena de la Vega L, Miller RS, Benda MM. et al. Association of Heparin-Dependent Antibodies and Adverse Outcomes in Hemodialysis Patients: A Population-Based Study. Mayo Clin Proc 2005; 80: 995-1000 doi:https://doi.org/10.4065/80.8.995
    CrossrefPubMedGoogle Scholar
  • 10 Gordon LA, Perkins HA, Richards V. Studies in regional heparinization. I. The use of simultaneous neutralization with protamine; preliminary studies. N Engl J Med 1956; 255: 1025-1029 doi:10.1056/NEJM195611292552202
    CrossrefPubMedGoogle Scholar
  • 11 Kozik-Jaromin J, Nier V, Heemann U. et al. Citrate pharmacokinetics and calcium levels during high-flux dialysis with regional citrate anticoagulation. Nephrol Dial Transplant 2009; 24: 2244-2251 doi:10.1093/ndt/gfp017
    CrossrefPubMedGoogle Scholar
  • 12 Gritters M, Grooteman MP, Schoorl M. et al. Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis. Nephrol Dial Transplant 2006; 21: 153-159 doi:10.1093/ndt/gfi069
    CrossrefPubMedGoogle Scholar
  • 13 Calatzis A, Toepfer M, Schramm W. et al. Citrate anticoagulation for extracorporeal circuits: effects on whole blood coagulation activation and clot formation. Nephron 2001; 89: 233-236 doi:10.1159/000046075
    CrossrefPubMedGoogle Scholar
  • 14 Davenport A, Tolwani A. Citrate anticoagulation for continuous renal replacement therapy (CRRT) in patients with acute kidney injury admitted to the intensive care unit. NDT Plus 2009; 2: 439-447 doi:10.1093/ndtplus/sfp136
    PubMedGoogle Scholar
  • 15 Bauer E, Derfler K, Joukhadar C, Druml W. Citrate kinetics in patients receiving long-term hemodialysis therapy. Am J Kidney Dis 2005; 46: 903-907 doi:10.1053/j.ajkd.2005.07.041
    CrossrefPubMedGoogle Scholar
  • 16 Kramer L, Bauer E, Joukhadar C. et al. Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med 2003; 31: 2450-2455 doi:10.1097/01.CCM.0000084871.76568.E6
    CrossrefPubMedGoogle Scholar
  • 17 Schwarzer P, Kuhn SO, Stracke S. et al. Discrepant post filter ionized calcium concentrations by common blood gas analyzers in CRRT using regional citrate anticoagulation. Crit Care 2015; 19: 321 doi:10.1186/s13054–015-1027–1
    CrossrefPubMedGoogle Scholar
  • 18 Section 5: Dialysis Interventions for Treatment of AKI Kidney Int Suppl (2011) 2012; 2: 89-115 doi:10.1038/kisup.2011.35
  • 19 Morita Y, Johnson RW, Dorn RE, Hall DS. Regional anticoagulation during hemodialysis using citrate. Am J Med Sci 1961; 242: 32-43
    CrossrefPubMedGoogle Scholar
  • 20 Pinnick RV, Wiegmann TB, Diederich DA. Regional Citrate Anticoagulation for Hemodialysis in the Patient at High Risk for Bleeding. N Engl J Med 1983; 308: 258-261 doi:10.1056/nejm198302033080506
    CrossrefPubMedGoogle Scholar
  • 21 Apsner R, Buchmayer H, Lang T. et al. Simplified citrate anticoagulation for high-flux hemodialysis. Am J Kidney Dis 2001; 38: 979-987 doi:10.1053/ajkd.2001.28584
    CrossrefPubMedGoogle Scholar
  • 22 Apsner R, Buchmayer H, Gruber D, Sunder-Plassmann G. Citrate for long-term hemodialysis: Prospective study of 1,009 consecutive high-flux treatments in 59 patients. Am J Kidney Dis 2005; 45: 557-564 doi:https://doi.org/10.1053/j.ajkd.2004.12.002
    CrossrefPubMedGoogle Scholar
  • 23 Gubenšek J, Kovač J, Benedik M. et al. Long-Term Citrate Anticoagulation in Chronic Hemodialysis Patients. Ther Apher Dial 2011; 15: 278-282 doi:10.1111/j.1744–9987.2011.00951.x
    CrossrefPubMedGoogle Scholar
  • 24 Gubensek J, Orsag A., Ponikvar R, Buturovic-Ponikvar J. Calcium Mass Balance during Citrate Hemodialysis: A Randomized Controlled Trial Comparing Normal and Low Ionized Calcium Target Ranges. PLoS One 2016; 11: e0168593 doi:10.1371/journal.pone.0168593
    CrossrefPubMedGoogle Scholar
  • 25 Hendrickx L, Kuypers D, Evenepoel P. et al. A comparative prospective study on the use of low concentrate citrate lock versus heparin lock in permanent dialysis catheters. Int J Artif Organs 2001; 24: 208-211
    CrossrefPubMedGoogle Scholar
  • 26 Leung KC, Tai DJ, Ravani P. et al. Citrate vs. acetate dialysate on intradialytic heparin dose: A double blind randomized crossover study. Hemodial Int 2016; 20: 537-547 doi:10.1111/hdi.12433
    CrossrefPubMedGoogle Scholar
  • 27 Stegmayr BG, Jonsson P, Mahmood D. A significant proportion of patients treated with citrate containing dialysate need additional anticoagulation. Int J Artif Organs 2013; 36: 1-6 doi:10.5301/ijao.5000172
    PubMedGoogle Scholar
  • 28 Aniort J, Petitclerc T, Créput C. Safe Use of Citric Acid-Based Dialysate and Heparin Removal in Postdilution Online Hemodiafiltration. Blood Purif 2012; 34: 336-343 doi:10.1159/000345342
    CrossrefPubMedGoogle Scholar
  • 29 Richtrova P, Mares J, Kielberger L. et al. Citrate-Buffered Dialysis Solution (Citrasate) Allows Avoidance of Anticoagulation During Intermittent Hemodiafiltration-At the Cost of Decreased Performance and Systemic Biocompatibility. Artif Organs 2017; 41: 759-766 doi:10.1111/aor.12851
    CrossrefPubMedGoogle Scholar
  • 30 Meijers B, Metalidis C, Vanhove T. et al. A noninferiority trial comparing a heparin-grafted membrane plus citrate-containing dialysate versus regional citrate anticoagulation: results of the CiTED study. Nephrol Dial Transplant 2017; 32: 707-714 doi:10.1093/ndt/gfw461
    CrossrefPubMedGoogle Scholar