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Abstract

Introduction: Fondaparinux is contraindicated in patients with severe renal impairment and renal failure due to an increased risk of bleeding. Dosing recommendations in this high-risk patient population, including the role of therapeutic drug monitoring using anti-Xa levels, are lacking. Methods: A retrospective chart review was conducted from October 1, 2006 to November 30, 2012. Subjects were identified based on ICD-9 procedure and diagnosis codes for renal insufficiency and RRT. Patients included were at least 18 years old, received prophylactic fondaparinux for 72 hours, received ≥ 1 dose in an intensive care unit, and had a CrCl < 30 mL/min or RRT during therapy. Subjects included were divided into 3 cohorts: CrCl < 30 mL/min without RRT, hemodialysis (HD), or continuous veno-venous hemofiltration (CVVH). Outcomes included the incidence of clinically significant bleeding and VTE. Patients were screened for bleeding and VTE events using ICD-9 codes and validated via chart review. Fondaparinux dose, dosing frequency, and anti-Xa level monitoring are described. The prophylactic fondaparinux anti-Xa range is 0.39-0.5 mcg/mL per our laboratory assay. Results: Thirty-one patients with severe renal impairment were included. Ten (32.3%) patients had a CrCl < 30 mL/min, 16 (51.6%) required CVVH, and 5 (16.1%) HD. The median defined daily dose in the CrCl < 30 mL/min without RRT, HD, and CVVH cohorts was 2.5 mg, 0.9 mg, and 1.9 mg, respectively. Anti-Xa monitoring occurred in 15 (48.4%) patients, most in the CVVH cohort (67%). Only 61% of anti-Xa levels were obtained 3-5 hours post dose. Median anti-Xa serum concentrations in the CrCl < 30 mL/min without RRT, HD, and CVVH cohorts were 0.2, 0.4, and 0.4 mcg/mL. Two (6.5%) patients experienced clinically significant bleeds. Both were receiving RRT and neither underwent anti-Xa monitoring. No patients experienced a VTE post fondaparinux initiation. Conclusions: Optimal fondaparinux dose and dosing frequency in patients with severe renal impairment is unknown and practice is variable. Anti-Xa monitoring may be beneficial to guide therapy in high-risk populations. Additional data is needed to recommend fondaparinux dosing strategies in critically ill patients with severe renal impairment.