title: Anticoagulation with fondaparinux for hemodiafiltration in patients with heparin-induced thrombocytopenia: dose-finding study and safety evaluation.
abstract: The optimal anticoagulation regimen for hemodialysis (HD) in patients with heparin-induced thrombocytopenia (HIT) has not been defined. Hemodiafiltration (HDF) adds a large convective component to HD, thereby changing the pharmacokinetics of most anticoagulants. Data on coagulation regimens for HDF are scant. We therefore aimed to study the feasibility, effectiveness, tolerability, and pharmacokinetics of fondaparinux anticoagulation in HDF. This was a prospective observational dose-finding study. Patients were started on fondaparinux at a dose of 0.05 mg/kg postdialysis body weight. Per protocol dose escalation was performed when significant clotting was observed and reduced when the anti-Xa activity postdialysis exceeded 0.4 IU/mL. Dose adjustments were made by steps of 0.01 mg/kg postdialysis weight. Anti-Xa activity was measured using a chromogenic method calibrated with low-molecular-weight heparin and validated against fondaparinux-calibrated anti-Xa activity. Four patients with HIT were followed for 160 sessions in total. At the end of the dose titration study, three patients ended at a maintenance dose of 0.03 mg/kg and one patient at 0.04 mg/kg of fondaparinux. Significant bleeding attributable to fondaparinux did not occur. The occurrence of clotting increased parallel to the reduction of fondaparinux dose, from 0/53 and 0/15 sessions at the higher doses (0.04 and 0.05 mg/kg) to 3/75 (4%) at 0.03 mg/kg and 1/17 (6%) at 0.02 mg/kg. Fondaparinux may be safely used and provides adequate anticoagulation for HDF in patients with HIT. We recommend to adjust dosage of fondaparinux to body weight and to initiate therapy at a dose of 0.03 mg/kg to prevent accumulation. Dose titration can be achieved by targeting postdialysis anti-Xa activity.
authors: Department of Nephrology, University Hospitals Leuven, Leuven, Belgium.
authors: Elien
authors: E
authors: Mahieu
authors: Kathleen
authors: K
authors: Claes
authors: Marc
authors: M
authors: Jacquemin
authors: Pieter
authors: P
authors: Evenepoel
authors: Karel
authors: K
authors: Op De Beek
authors: Anne-Marie
authors: AM
authors: Bogaert
authors: Dirk
authors: D
authors: Kuypers
authors: Peter
authors: P
authors: Verhamme
authors: Björn
authors: B
authors: Meijers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001530:Belgium; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D057915:Drug Substitution; D065427:Factor Xa Inhibitors; D005240:Feasibility Studies; D005260:Female; D000077425:Fondaparinux; D017583:Hemodiafiltration; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011134:Polysaccharides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011134:Polysaccharides; D006493:Heparin; D000077425:Fondaparinux