title: Prevention of clot formation during haemodialysis using the direct thrombin inhibitor melagatran in patients with chronic uraemia.
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.
  
  
  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 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.
  
  
  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.
authors.affiliation: Department of Nephrology, Sahlgrenska University Hospital, SE 41345 Göteborg, Sweden. per-ola.attman@vgregion.se
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Attman
authors.forename: Pia
authors.initials: P
authors.lastname: Ottosson
authors.forename: Ola
authors.initials: O
authors.lastname: Samuelsson
authors.forename: Ulf G
authors.initials: UG
authors.lastname: Eriksson
authors.forename: Maria
authors.initials: M
authors.lastname: Eriksson-Lepkowska
authors.forename: Gunnar
authors.initials: G
authors.lastname: Fager
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D000991:Antithrombins / Q000627:therapeutic use; D001384:Azetidines; D001596:Benzylamines; D002908:Chronic Disease; D017985:Dalteparin / Q000627:therapeutic use*; D005998:Glycine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D019934:International Normalized Ratio; D007676:Kidney Failure, Chronic / Q000628:therapy; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D014511:Uremia / Q000097:blood* / Q000628:therapy*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001384:Azetidines; D001596:Benzylamines; C109573:melagatran; D017985:Dalteparin; D005998:Glycine