Fondaparinux in Critically Ill Patients With Renal Failure

We will be studying fondaparinux 2.5 mg subcutaneously every 48 hr in three distinct patient groups: 1) Acute kidney failure without hemodialysis, 2) Acute kidney failure (AKI) with intermittent hemodialysis (IHD) and 3) Acute renal failure with continuous renal replacement therapy (CRRT). All patients will be assessed for efficacy of the dose. Efficacy will be assessed by following clinically for any evidence of VTE, either deep venous thrombosis (DVT) or pulmonary embolism. In addition, lower extremity duplex studies will be performed at baseline and at the end of the study period to assess for DVT.

Secondary objectives will be safety and accumulation. Safety will be determined by assessment of clinically significant bleeding, defined as a drop in Hgb of > 2 grams (gm) in 24 hr, or the need for red blood cell transfusion related to bleeding. Accumulation may occur in renal failure and will be studied throughout the intensive care unit (ICU) stay through reevaluation of levels over time.

Inclusion criteria

• Age ≥ 18 years old and ≤ 89 years old
• Body weight ≥ 50 kg or ≤ 150 kg
• Estimated creatinine clearance of < 30 mL/min
• Predicted ICU stay of more than 72 hours.

Exclusion criteria

• Pregnant women
• Infective Endocarditis
• Neuraxial anesthesia or spinal puncture
• Active bleeding
• Treatment with vitamin K antagonists or therapeutic doses of unfractionated heparin
• Signs of disseminated intravascular coagulation
• Severe liver failure (serum bilirubin > 5 mg/dL)
• Surgery planned within 24 hours of ICU admission
• Latex allergy