Abstract: TH-PO194

Recurrent Venous Thromboembolism (VTE) in Membranous Nephropathy despite Direct Xa Inhibitor Therapy

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Reynolds, Monica Lona, University North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Derebail, Vimal K., University North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Background

In membranous nephropathy, the risk of VTE is high and increases significantly with a serum albumin of <2.8 g/dl. Apixaban, a direct factor Xa inhibitor, is non-inferior to warfarin for VTE treatment in the general population but has not been studied in the nephrotic syndrome. We report a patient with recurrent VTE while on therapeutic dosing of apixaban.

Methods

A 51-year-old Caucasian male presented with new hypertension and lower extremity edema. Imaging studies demonstrated bilateral pulmonary emboli and acute DVT of the left external iliac, femoral and popliteal vein with extension to the IVC. After mechanical thrombectomy and catheter-directed thrombolytics, he was placed on apixaban 2.5mg BID. Edema recurred two months later and CT demonstrated extension of clot. He was switched to fondaparinux and referred to Hematology. Serum albumin was 2.1 g/dl and urinalysis showed proteinuria. Urine protein to creatinine ratio was 13 g/g.
Catheter-directed thrombolytics and mechanical thrombectomy were repeated. Thrombophilia work-up was negative for Antithrombin and Protein C/S deficiency. He was discharged on apixaban 5 mg BID as prior dosing was thought to be sub-therapeutic. Anti-Phospholipase A2 receptor (PLA2R) antibody titers were 424 RU/ml, and he was presumed to have membranous nephropathy. Given the need for anticoagulation and recent thrombolytics, renal biopsy was deferred. He was treated with alternating monthly corticosteroids and oral cyclophosphamide.
Six months later, UPC was 5 g/g and serum albumin was 2.6 g/dl. Repeat PLA2R antibody was <2 RU/ml. However, D-dimer was elevated to 2345 ng/mL and doppler ultrasonography revealed left acute mid femoral DVT and acute on chronic proximal femoral DVT. Four-hour apixaban drug level was 50.4 ng/ml (mean peak value in healthy volunteers- 128.5 ng/ml). He was switched back to fondaparinux. At one year, he had no further VTE’s and serum albumin was 3.3 g/dl.

Conclusion

Despite appropriate dosing of apixaban, our patient developed recurrent VTE. A four-hour drug level was below the range reported for healthy volunteers at the same dose. Due to its high protein binding, apixaban may have altered pharmacokinetics and pharmacodynamics in patients with nephrotic syndrome and hypoalbuminemia. More data is needed to determine appropriate use of novel oral anticoagulants in the nephrotic syndrome.