Thromb Haemost 2007; 98(06): 1200-1207
DOI: 10.1160/TH07-07-0444
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Use of the pentasaccharide fondaparinux as an anticoagulant during haemodialysis

Robert M. Kalicki
1   Department of Nephrology and Hypertension, Inselspital, University of Bern, Switzerland
,
Fabienne Aregger
1   Department of Nephrology and Hypertension, Inselspital, University of Bern, Switzerland
,
Lorenzo Alberio
2   Division of Haematology and Central Haematology Laboratory, Inselspital, University of Bern, Switzerland
,
Bernhard Lämmle
2   Division of Haematology and Central Haematology Laboratory, Inselspital, University of Bern, Switzerland
,
Felix J. Frey
1   Department of Nephrology and Hypertension, Inselspital, University of Bern, Switzerland
,
Dominik E. Uehlinger
1   Department of Nephrology and Hypertension, Inselspital, University of Bern, Switzerland
› Author Affiliations
Further Information

Publication History

Received 06 July 2007

Accepted after revision 22 September 2007

Publication Date:
30 November 2017 (online)

Summary

No data about the use of the pentasaccharide fondaparinux, a highly selective indirect inhibitor of factor Xa,in patients treated with haemodialysis are available. Therefore, we investigated the pharmacokinetics and -dynamics of fondaparinux in 12 patients during haemodialysis. The anti-Xa activity (expressed as fondaparinux equivalent) was monitored, a semiquantitative clotting scale (SQCS) ranging from 0 (no visible traces of coagula) to 3 (complete clotting of the dialysis circuit) was applied, and the digital compression time necessary to achieve haemostasis at the puncture site was determined. After an initial period, when the regular heparin dose was replaced once weekly by fondaparinux, 0.05 mg/kg, the pentasaccharide was administered for nine consecutive haemodialysis sessions. Peak anti-Xa activity increased from 0.61 ± 0.14 μg/l after the first dose to 0.89 ± 0.24 μg/l after dose 9 (P<0.001), whereas predialysis anti-Xa activity steadily rose to 0.32 ± 0.09 μg/l (P<0.001). A sufficient but slightly less effective anticoagulation with a mean SQCS of 1.19 ± 0.71 (n=121) was obtained by fondaparinux as compared with 0.65 ± 0.58 (n=60, P<0.005) by 4,825 ± 1,703 U of unfractionated heparin. Mean digital compression time rose slightly during fondaparinux from 23.7 ± 7.4 minutes to 24.8 ± 7.5 minutes (P<0.05) and, more important, six of the 12 patients reported minor bleeding problems during the interdialytic interval. Thus, fondaparinux can be used to prevent circuit clotting during haemodialysis; however, accumulation results in an interdialytic increase of anti-Xa activity. Therefore, fondaparinux should be reserved for patients requiring systemic anticoagulation on the days off dialysis.

 
  • References

  • 1 Ambuhl PM, Wuthrich RP, Korte W. et al. Plasma hypercoagulability in haemodialysis patients: impact of dialysis and anticoagulation. Nephrol Dial Transplant 1997; 12: 2355-2364.
  • 2 Sagedal S, Hartmann A, Sundstrom K. et al. Anticoagulation intensity sufficient for haemodialysis does not prevent activation of coagulation and platelets. Nephrol Dial Transplant 2001; 16: 987-993.
  • 3 Perry SL, O’Shea SI, Byrne S. et al. A multi-dose pharmacokinetic study of dalteparin in haemodialysis patients. Thromb Haemost 2006; 96: 750-755.
  • 4 Schmitt Y, Schneider H. Low-molecular-weight heparin (LMWH): influence on blood lipids in patients on chronic haemodialysis. Nephrol Dial Transplant 1993; 8: 438-442.
  • 5 Schrader J, Stibbe W, Armstrong VW. et al. Comparison of low molecular weight heparin to standard heparin in hemodialysis/hemofiltration. Kidney Int 1988; 33: 890-896.
  • 6 Schrader J, Andersson LO, Armstrong VW. et al. Lipolytic effects of heparin and low molecular weight heparin and their importance in hemodialysis. Semin Thromb Hemost 1990; 16 Suppl 41-45.
  • 7 Stefoni S, Cianciolo G, Donati G. et al. Standard heparin versus low-molecular-weight heparin. A medium- term comparison in hemodialysis. Nephron 2002; 92: 589-600.
  • 8 Wiemer J, Scherberich JE. When lipids increase in dialysis: the role of heparin! Standard heparin increases low-molecular-weight heparin lowers triglycerides. MMW Fortschr Med 1999; 141: 29-32.
  • 9 Wiemer J, Winkler K, Baumstark M. et al. Influence of low molecular weight heparin compared to conventional heparin for anticoagulation during haemodialysis on low density lipoprotein subclasses. Nephrol Dial Transplant 2002; 17: 2231-2238.
  • 10 Pettila V, Leinonen P, Markkola A. et al. Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb Haemost 2002; 87: 182-186.
  • 11 11.. Handschin AE, Trentz OA, Hoerstrup SP, Kock HJ, Wanner GA, Trentz O. Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra) on human osteoblasts in vitro. Br J Surg 2005; 92: 177-183.
  • 12 Sarris E, Tsele E, Bagiatoudi G. et al. Diffuse alopecia in a hemodialysis patient caused by a low-molecular- weight heparin, tinzaparin. Am J Kidney Dis 2003; 41: E15.
  • 13 Bredlich RO, Stracke S, Gall H. et al. Heparin-associated platelet aggregation syndrome with skin necrosis during hemodialysis. Dtsch Med Wochenschr 1997; 122: 328-332.
  • 14 Ludwig RJ, Schindewolf M, Utikal J. et al. Management of cutaneous type IV hypersensitivity reactions induced by heparin. Thromb Haemost 2006; 96: 611-617.
  • 15 Greinacher A, Farner B, Kroll H. et al. Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. A retrospective analysis of 408 patients. Thromb Haemost 2005; 94: 132-135.
  • 16 Gregorini G, Bellandi D, Martini G. et al. Heparininduced thrombocytopenia syndrome and thrombosis in patients undergoing periodic haemodialysis. G Ital Nefrol 2002; 19: 672-692.
  • 17 Lord H, Jean N, Dumont M. et al. Comparison between tinzaparin and standard heparin for chronic hemodialysis in a Canadian center. Am J Nephrol 2002; 22: 58-66.
  • 18 Momi S, Nasimi M, Colucci M. et al. Low molecular weight heparins prevent thrombin-induced thrombo- embolism in mice despite low anti-thrombin activity. Evidence that the inhibition of feed-back activation of thrombin generation confers safety advantages over direct thrombin inhibition. Haematologica 2001; 86: 297-302.
  • 19 Florian-Kujawski M, Hoppensteadt D, Maddineni J. et al. Differential regulation of thrombin activatable fibrinolytic inhibitor by low molecular weight heparins. Pharmacologic implications. Int Angiol 2004; 23: 346-354.
  • 20 Linkins LA, Julian JA, Rischke J. et al. In vitro comparison of the effect of heparin, enoxaparin and fondaparinux on tests of coagulation. Thromb Res 2002; 107: 241-244.
  • 21 Shinoda T, Arakura H, Katakura M. et al. Usefulness of thrombelastography for dosage monitoring of low molecular weight heparin and unfractionated heparin during hemodialysis. Artif Organs 1990; 14: 413-415.
  • 22 Farooq V, Hegarty J, Chandrasekar T. et al. Serious adverse incidents with the usage of low molecular weight heparins in patients with chronic kidney disease. Am J Kidney Dis 2004; 43: 531-537.
  • 23 Guillet B, Simon N, Sampol JJ. et al. Pharmacokinetics of the low molecular weight heparin enoxaparin during 48 h after bolus administration as an anticoagulant in haemodialysis. Nephrol Dial Transplant 2003; 18: 2348-2353.
  • 24 Bauersachs RM. Fondaparinux: an update on new study results. Eur J Clin Invest 2005; 35 (Suppl. 01) 27-32.
  • 25 Turpie AG, Eriksson BI, Lassen MR. et al. Fondaparinux, the first selective factor Xa inhibitor. Curr Opin Hematol 2003; 10: 327-332.
  • 26 Turpie AG. Fondaparinux: a Factor Xa inhibitor for antithrombotic therapy. Expert Opin Pharmacother 2004; 5: 1373-1384.
  • 27 D’Angelo A, Valle PD, Fattorini A. et al. Disappearance of anti-PF4/heparin antibodies under prolonged fondaparinux administration in a patient with DVT associated with LMWH-induced thrombocytopenia. Thromb Haemost 2006; 95: 573-575.
  • 28 Walenga JM, Jeske WP, Samama MM. et al. Fondaparinux: a synthetic heparin pentasaccharide as a new antithrombotic agent. Expert Opin Investig Drugs 2002; 11: 397-407.
  • 29 Bonneux IM, Bellemans J, Fabry G. Evaluation of wound healing after total knee arthroplasty in a randomized prospective trial comparing fondaparinux with enoxaparin. Knee 2006; 13: 118-121.
  • 30 Eknoyan G, Beck GJ, Cheung AK. et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002; 347: 2010-2019.