A multicenter prospective real-world cohort study of direct oral anticoagulant use for venous thromboembolism prophylaxis in nephrotic syndrome.

INTRODUCTION

Nephrotic syndrome (NS), especially when associated with severe hypoalbuminia, confers a high risk of venous thromboembolism (VTE). While low-molecular-weight heparin and warfarin are recommended by some guidelines for thromboprophylaxis in high risk patients, data supporting the use of direct oral anticoagulants for primary prophylaxis in NS remain limited and largely observational.

METHODS

We conducted a prospective multicentric cohort study across eight tertiary centers in India, enrolling adults (≥18 years) with NS and severe hypoalbuminia (albumin <2.4 g/dL for Membranous nephropathy; <2.0 g/dL for other etiologies). All patients received apixaban 5 mg once daily as primary VTE prophylaxis until albumin levels improved beyond 2.4 g/dL. The primary composite outcome included VTE occurrence and major or clinically significant bleeding events. Patients were followed until anticoagulation discontinuation.

RESULTS

A total of 212 patients were analyzed (mean age 36.9 ± 14.0 years, 52% male). Median proteinuria was 9.0 g/day and mean serum albumin 1.68 ± 0.49 g/dL; mean serum creatinine was 1.5 ± 0.54 mg/dL. Most patients were categorized as low (80%) or intermediate (20%) bleeding risk by GN tool. Membranous nephropathy was the most common etiology (45%). Immunosuppressive therapy included corticosteroids (81%), rituximab (25.9%), and cyclophosphamide (28.3%). The median duration of apixaban therapy was 90 days (IQR: 27–115 days). No venous or arterial thromboembolic events occurred, and minor bleeding was observed in 4 patients (3.5%), all resolving without transfusion or hospitalization. Overall apixaban was well tolerated.

CONCLUSION

In this large multicenter prospective cohort of patients with NS and severe hypoalbuminemia, apixaban use for primaryVTE was associated with a low incidence of thromboembolic and bleeding events. While these findings provide important real-world safety and feasibility data, randomized controlled trials are required to establish efficacy, optimal dosing, and patient selection for DOAC-based VTE in NS. CLINICAL TRIAL NUMBER: Not applicable.