Thromboprophylaxis with fondaparinux in high-risk postoperative patients with renal insufficiency

Details

• Alternative Title:
  Thromb Res
• Personal Author:
  Hester, Willie ; Fry, Caitlyn ; Gonzalez, Daniel ; Cohen-Wolkowiez, Michael ; Inman, Brant A. ; Ortel, Thomas L.
• Description:
  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.
• Keywords:
  Aged Aged, 80 And Over Anticoagulants Fondaparinux Humans Male Middle Aged Polysaccharides Postoperative Period Prospective Studies Renal Failure Renal Insufficiency Risk Factors Thromboembolism Thromboprophylaxis

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• Source:
  Thromb Res. 133(4):629-633
• Pubmed ID:
  24508189
• Pubmed Central ID:
  PMC4156854
• Document Type:
  Journal Article
• Funding:
  U01 DD000014/DD/NCBDD CDC HHSUnited States/ ; U18 DD000014/DD/NCBDD CDC HHSUnited States/ ; GM086330/GM/NIGMS NIH HHSUnited States/ ; K23 HD064814/HD/NICHD NIH HHSUnited States/ ; T32 GM086330/GM/NIGMS NIH HHSUnited States/ ; 1K23HD064814/HD/NICHD NIH HHSUnited States/ ; DD-000014/DD/NCBDD CDC HHSUnited States/
• Volume:
  133
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:3221dd041d4b2271eec8f0bca756f77b2f6a91bec4ac1fdde43cd1d8ced43251
• Download URL:
  https://stacks.cdc.gov/view/cdc/30105/cdc_30105_DS1.pdf
• File Type:
  [PDF - 192.72 KB ]