Anticoagulation With Fondaparinux for Hemodiafiltration in Patients With Heparin‐Induced Thrombocytopenia: Dose‐Finding Study and Safety Evaluation

The optimal anticoagulation regimen for hemo- dialysis (HD) in patients with heparin-induced thromb- ocytopenia (HIT) has not been defined. Hemodiafiltration (HDF) adds a large convective component to HD, thereby changing the pharmacokinetics of most antico- agulants. Data on coagulation regimens for HDF are scant. We therefore aimed to study the feasibility, effec- tiveness, tolerability, and pharmacokinetics of fonda- parinux 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 postdialy- sis weight. Anti-Xa activity was measured using a chro- mogenic 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 ses- sions 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