Journal Article

Prevention of clot formation during haemodialysis using the direct thrombin inhibitor melagatran in patients with chronic uraemia

Per-Ola Attman, Pia Ottosson, Ola Samuelsson, Ulf G. Eriksson, Maria Eriksson-Lepkowska and Gunnar Fager

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 20, issue 9, pages 1889-1897
Published in print September 2005 | ISSN: 0931-0509
Published online May 2005 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh915
Prevention of clot formation during haemodialysis using the direct thrombin inhibitor melagatran in patients with chronic uraemia

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Background. This study assessed the feasibility of replacing intravenous (i.v.) dalteparin with the direct thrombin inhibitor (DTI) melagatran administered via dialysis fluid in patients undergoing haemodialysis, and also examined the pharmacokinetics of melagatran with and without dialysis.

Methods. During two 4 h haemodialysis sessions, 10 adult patients were administered i.v. dalteparin. During two subsequent sessions, melagatran was administered as an i.v. bolus before dialysis, and in the dialysis fluid. The pharmacokinetics of melagatran administered as a bolus before dialysis, and of i.v. melagatran during a dialysis-free day, were studied. Dialysis performances were evaluated from clinical criteria including clot formation in the dialyzer and bloodlines, pre-post dialyzer pressures and iohexol clearance. Anticoagulant efficacy was evaluated from dialysis success.

Results. All dialysis sessions were successful, with no apparent difference in clot formation between the two treatments. Median iohexol clearance was similar with dalteparin (99–103 ml/min) and melagatran in the dialysis fluid (98–100 ml/min). There was no difference in pre- and post-dialyzer bloodline pressures between the two treatments. During dialysis sessions with melagatran in dialysis fluid, melagatran concentrations in plasma rapidly equilibrated to ∼70% of those in dialysis fluid. While the clearance of melagatran was low in patients with renal failure (mean±SD, 0.93±0.36 l/h), haemodialysis provided efficient clearance of melagatran (7.20±0.76 l/h). Melagatran clearance by dialysis (104±10 ml/min) was comparable to iohexol clearance.

Conclusions. The DTI melagatran administered via dialysis fluid may provide sufficient anticoagulation for haemodialysis. Melagatran is rapidly cleared from plasma by haemodialysis, suggesting that this method may be used to decrease drug levels in patients with renal impairment.

Keywords: anticoagulant; chronic uraemia; haemodialysis; melagatran; thrombosis; ximelagatran

Journal Article.  5042 words.  Illustrated.

Subjects: Nephrology

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