title: Clinical experience with prophylactic fondaparinux in critically ill patients with moderate to severe renal impairment or renal failure requiring renal replacement therapy.
abstract: BACKGROUND
  Fondaparinux has an increased bleeding risk in patients with a CrCl ≤ 50 mL/min and is contraindicated if CrCl < 30 mL/min. Data regarding dosing and anti-Xa monitoring are lacking in this population.
  
  
  OBJECTIVE
  To describe dosing, monitoring, and safety outcomes of prophylactic fondaparinux in critically ill patients with moderate to severe renal impairment, including renal replacement therapy (RRT).
  
  
  METHODS
  Retrospective analysis from October 2006 to November 2012 of patients ≥ 18 years old who received fondaparinux for ≥ 72 hours with ≥ 1 dose in an intensive care unit and a CrCl ≤ 50 mL/min or RRT during therapy. Participants were divided into 4 cohorts: moderate impairment (CrCl = 30-50 mL/min), severe impairment (CrCl < 30 mL/min), hemodialysis (HD), or continuous venovenous hemofiltration (CVVH). Outcomes included the incidence of clinically significant bleeding and thromboembolic events. Fondaparinux dose, dosing frequency, and anti-Xa level monitoring are described. Pharmacokinetic modeling was performed to assess drug accumulation.
  
  
  RESULTS
  In all, 95 patients met inclusion criteria: 64 (67.4%) with moderate impairment, 10 (10.5%) with severe impairment, 5 (5.3%) with HD, and 16 (16.8%) with CVVH. The median defined daily doses in the moderate, severe, HD, and CVVH cohorts were 2.5, 2.5, 0.9, and 1.9 mg. Anti-Xa monitoring occurred in 19 (20%) patients, although few concentrations were peaks. Clinically significant bleeding occurred in 4 (4.2%) patients. A pharmacokinetic model demonstrated drug accumulation.
  
  
  CONCLUSIONS
  Empirical dose adjustments may be prudent in critically ill patients with renal dysfunction; however, the optimal fondaparinux dosage in this population remains unknown. Peak anti-Xa concentrations may help guide therapy.
authors.affiliation: UF Health Shands Hospital, Gainesville, FL, USA copej@shands.ufl.edu.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cope
authors.affiliation: Barnes-Jewish Hospital, St Louis, MO, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bushwitz
authors.affiliation: University of Florida, Orlando, FL, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: An
authors.affiliation: UF Health Shands Hospital, Gainesville, FL, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Antigua
authors.affiliation: University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Anjan
authors.initials: A
authors.lastname: Patel
authors.affiliation: University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Zumberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D018890:Chemoprevention; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D000077425:Fondaparinux; D006440:Hemofiltration; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006495:Heparin, Low-Molecular-Weight / Q000097:blood; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D011134:Polysaccharides / Q000627:therapeutic use*; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000601:surgery*; D017582:Renal Replacement Therapy; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D011134:Polysaccharides; D000077425:Fondaparinux
keywords: anti-Xa monitoring; dialysis; fondaparinux; heparin-induced thrombocytopenia; major bleeding; renal impairment