title: Thromboprophylaxis with fondaparinux in high-risk postoperative patients with renal insufficiency.
abstract: Fondaparinux is an antithrombin-dependent factor Xa inhibitor that is used for thromboprophylaxis of patients undergoing hip fracture surgery, hip or knee replacement, or abdominal surgery. It is cleared by the kidney and should be used with caution in patients with renal impairment and avoided in patients with severe renal insufficiency. Recently, several studies have demonstrated that a lower dose of fondaparinux in patients with moderate renal impairment appears to be safe and effective. The purpose of this study was to obtain pharmacokinetic and clinical data on the use of prophylactic fondaparinux in patients with renal insufficiency undergoing major abdominal surgery for cancer (n=8) or orthopedic surgery (n=1). Anti-factor Xa levels were obtained, and a published population pharmacokinetic model for fondaparinux was fit to the data. The data were analyzed using NONMEM software. Fondaparinux did not appear to accumulate in these patients, even when the drug was administered for up to twelve days. Pharmacokinetic analysis revealed that the apparent clearance in this population, who were primarily undergoing cancer surgery, was similar to prior studies in orthopedic surgery patients. In contrast, lower estimates were obtained for volume of distribution and absorption rate constant parameters. None of the patients sustained a hemorrhagic complication attributable to fondaparinux. One patient developed hypoxia in the setting of transient atrial fibrillation and clinical suspicion for pulmonary embolism, but this was not confirmed radiographically. These results support the use of 1.5mg of fondaparinux every 24hours for thromboprophylaxis in patients with renal insufficiency undergoing high-risk surgical procedures.
authors: Metrolina Nephrology Associates, Mooresville, NC, USA.
authors: Willie
authors: W
authors: Hester
authors: Hemostasis and Thrombosis Center, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors: Caitlyn
authors: C
authors: Fry
authors: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors: Daniel
authors: D
authors: Gonzalez
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA; Department of Pediatrics, Duke University, Durham, NC, USA.
authors: Michael
authors: M
authors: Cohen-Wolkowiez
authors: Division of Urology, Department of Surgery, Duke University Medical Center, Durham, NC, USA.
authors: Brant A
authors: BA
authors: Inman
authors: Hemostasis and Thrombosis Center, Department of Medicine, Duke University Medical Center, Durham, NC, USA; Department of Pathology, Duke University Medical Center, Durham, NC, USA. Electronic address: thomas.ortel@duke.edu.
authors: Thomas L
authors: TL
authors: Ortel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000077425:Fondaparinux; D006801:Humans; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011184:Postoperative Period; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000378:metabolism*; D012307:Risk Factors; D013923:Thromboembolism / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D011134:Polysaccharides; D000077425:Fondaparinux
keywords: Fondaparinux; Renal failure; Thromboprophylaxis