Aaron Knopp, PharmD, BCPS, BCCCP
Critical Care Clinical Pharmacy Specialist
Rhode Island Hospital
Providence, Rhode Island
Disclosure information not submitted.
Abdalla Ammar, PharmD, BCCCP, BCPS,
Critical Care Pharmacist, Neurocritical Care
New York Presbyterian Hospital - Weill Cornell Medical College
New York, NY
Disclosure information not submitted.
Ginger Rouse, BCCCP, PharmD, BCPS,
Clinical Pharmacy Specialist II, Medical Intensive Care
Yale New Haven Hospital
New Haven, Connecticut
Disclosure information not submitted.
Lydia Tran, PharmD, BCPS
Senior Clinical Pharmacy Specialist
Yale New Haven Hospital, United States
Disclosure information not submitted.
Mahmoud Ammar, BCCCP, PharmD, BCPS,
Critical Care Pharmacist
Yale New Haven Hospital
New Haven, Connecticut
Disclosure information not submitted.
Title: Safety and Efficacy of Fondaparinux in Renal Insufficiency Utilizing Anti-Xa Monitoring
Introduction: Fondaparinux (FX) is a synthetic anticoagulant that prevents thrombin formation and development through factor Xa inhibition. FX is contraindicated in patients with impaired renal function, yet small reports suggest predictable outcomes of an extended interval dosing regimen for venous thromboembolism (VTE) prophylaxis. This study aims to evaluate the safety and efficacy of an anti-Xa monitoring protocol for extended interval FX dosing for VTE prophylaxis in renal insufficiency.
Methods: Medical records of adult patients admitted to a five-hospital health system between January 1, 2017 and December 31, 2019 who received at least one dose of FX 2.5 mg every 48 hours with renal impairment [CrCl < 30 mL/min, acute kidney injury (AKI), or renal replacement therapy (RRT)] and at least one appropriately timed anti-Xa level (peak or trough) were included. Primary outcome evaluated was efficacy defined as anti-Xa peak measured 3-5 hours post-dose between 0.39 and 0.5 mg/L or trough measured 47-49 hours post-dose of < 0.27 mg/L. Duration of FX exposure and level frequency were assessed as secondary outcomes. Safety outcomes evaluated included incidence of bleeding events or thrombosis within 14 days post-FX administration.
Results: Forty-two patients were screened for inclusion (n=17) with a total of 47 anti-Xa levels. Only 51.1% (n=24) of anti-Xa levels were drawn appropriately and included for analysis, 75% (n=18) peaks and 25% (n=6) troughs. Chronic kidney disease was the most frequent renal function at therapy initiation (41.2%), followed by AKI (35.3%) and RRT (23.5%). Anti-Xa within goal range was observed in 41.7% of levels (n=10), encompassing 22.2% (n=4) of included peak levels and all included trough levels (n=6). Ten anti-Xa peak levels (55.6%) were below goal range and 4 (22.2%) were above goal range. Median (IQR) peak anti-Xa was 0.44 mg/L (0.27-0.58) and trough 0.14 mg/L (0.13-0.21). Patients received a median (IQR) 3 doses (2-10) of FX correlating with 6 days (4-13) of therapy. The safety endpoint of bleeding events occurred in 17.6% (n=3) while there were no thrombotic events.
Conclusion: Extended interval FX for VTE prophylaxis in renal insufficiency is potentially effective at preventing thrombosis. Larger studies are warranted to determine optimal dosing balanced with risk of bleeding.