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

Authors :
Attman PO
Ottosson P
Samuelsson O
Eriksson UG
Eriksson-Lepkowska M
Fager G
Source :
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2005 Sep; Vol. 20 (9), pp. 1889-97. Date of Electronic Publication: 2005 May 31.
Publication Year :
2005

Abstract

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.<br />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.<br />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 approximately 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.<br />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.

Details

Language :
English
ISSN :
0931-0509
Volume :
20
Issue :
9
Database :
MEDLINE
Journal :
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Publication Type :
Academic Journal
Accession number :
15928099
Full Text :
https://doi.org/10.1093/ndt/gfh915