Safety and effectiveness of direct oral anticoagulants in patients with nephrotic syndrome: a report of 21 cases.

BACKGROUND: Nephrotic syndrome (NS) is associated with increased risk of thromboembolic events (TE) adding to the morbidity and mortality. International guidelines recommend prophylactic anticoagulation in patients with NS and high risk of TE, but no studies have identified the optimal type of anticoagulation in NS. We aimed to assess the effectiveness and safety of direct oral anticoagulant (DOAC) by analyzing the thromboembolic and bleeding events in NS patients prescribed DOAC as primary prophylaxis to prevent TE or as treatment for TE occurring in relation to NS. METHODS: We performed a single-center, retrospective study including patients with NS, a plasma albumin less than 25 g/L and prophylactic anticoagulation treatment with DOAC at the Department of Renal Medicine at Aarhus University Hospital, Denmark from July 2016 to June 2021. Patients treated with DOAC as thromboprophylaxis for other indications than NS were excluded. Baseline characteristics and outcomes, including TE, bleeding and other adverse effects associated with DOAC were obtained from medical records. RESULTS: We identified 268 patients treated with DOAC of which 21 patients with NS were included in the study. Nineteen patients were prescribed DOAC as thromboprophylaxis and two patients received DOAC due to previous TE, which was considered associated with the NS. The type of DOAC prescribed was apixaban (n = 10) and rivaroxaban (n = 11). No patients experienced TE during DOAC treatment, while five patients had a minor bleeding episode. Patients who experienced bleeding episodes were older (median 62 vs 51 years), more often female (80%) and had been on DOAC for a longer period (204 days vs 47 days). Neither the HAS-BLED score nor GN-risk-score predicted the risk of minor bleedings in this population. CONCLUSIONS: In this case series, no new TE and only minor bleeding complications were observed among adult NS patients treated with DOAC.

Prophylactic anticoagulation in nephrotic syndrome prevents thromboembolic complications.

BACKGROUND: An increased incidence of thromboembolic events (TE) are reported in nephrotic syndrome (NS) leading to recommendations for prophylactic anticoagulation (PAC). However, as no randomized clinical trial has established the efficacy or risks associated with PAC, guidelines are empiric or substantiated only by estimates of risks and benefits. This study evaluates the risk of TE and hemorrhagic complications in patients with NS treated with PAC and compares to patients not receiving PAC. METHODS: We included patients diagnosed with NS from two Danish nephrology departments with different practices for the use of PAC. Patients were included if presenting with NS from September 2006 to January 2012, a P-albumin < 30 g/L, and renal biopsy confirming non-diabetic, glomerular disease. Patients aged < 16 years, on renal replacement therapy, or administered anticoagulants at the onset of NS were excluded. Bleeding episodes and/or TE were identified from patient records. Bleeding episodes were divided into minor and major bleeding. RESULTS: Of the 79 patients included, 44 patients received PAC either as low or high dose low-molecular-weight heparin (LMWH) or as warfarin with or without LMWH as bridging, while 35 did not receive PAC. P-albumin was significant lower in the PAC group compared to those not receiving PAC. Significantly more TEs was observed in the non-PAC group compared to the PAC group (4 versus 0 episodes, P = 0.035). The TEs observed included one patient with pulmonary embolism (PE), one with PE and deep vein thrombosis, one with PE and renal vein thrombosis, and one with a stroke. Five patients with bleeding episodes were identified among those receiving PAC, of which two were major and three were minor, while two patients in the non-PAC group experienced a minor bleeding episode (P = 0.45 between groups). The major bleeding episodes only occurred in patients receiving PAC in combination with low dose aspirin. CONCLUSIONS: In patients with NS the use of PAC was associated with a decreased risk of clinically significant TE, but may also be associated with more bleeding episodes although not statistically significant. Only patients treated with PAC in combination with anti-platelet therapy had major bleeding episodes.