Apixaban Concentrations and Effects on Coagulation in Patients With Nephrotic Syndrome.

Rationale & Objective: Venous thromboembolism is a serious complication of nephrotic syndrome (NS). Guidelines recommend prophylactic anticoagulation with warfarin or low molecular weight heparin. Although widely used for other conditions, data on direct oral anticoagulants in NS are limited. We explored the potential of standard-dose apixaban by assessing its steady-state concentrations and anticoagulant effects in patients with NS. Study Design: An open-label, single-arm, controlled interventional clinical trial. Setting & Participants: The study included adult patients with NS (plasma albumin levels < 25 g/L and urine albumin-creatinine ratio > 2,200 mg/g) with a primary glomerular disease compared with healthy individuals. Interventions: Patients with NS received weight-adjusted dalteparin for at least 4 days, followed by a washout period of ≥ 24 hours, before starting apixaban 5 mg twice daily for a minimum of 4 days. Outcomes: The primary outcome was the steady-state plasma concentration of apixaban. Secondary outcomes included thrombin generation measured at baseline, during dalteparin steady-state, and at 2.5, 8, and 24 hours after the first apixaban dose, as well as at steady state. Results: Mean steady-state plasma apixaban level was significantly lower in patients with NS (n=11) than in healthy individuals (n=10) (35 μg/L, 95% CI, 28-43 vs 51 μg/L, 95% CI, 39-64; P = 0.02). Despite this, mean endogenous thrombin potential was comparable at steady-state (1,096 nM/min, 95% CI, 868-1,355 vs 910 nM/min, 95% CI, 713-1,107; P = 0.19). In patients with NS, apixaban reduced in vivo thrombin generation markers (prothrombin fragment 1+2 and thrombin-antithrombin complex) more effectively than dalteparin. Limitations: The small sample size and short study duration may limit the generalizability of the findings. Conclusions: Patients with NS demonstrated lower plasma apixaban concentrations but maintained comparable anticoagulant effects compared to healthy individuals. Apixaban showed greater suppression of in vivo thrombin generation than dalteparin. This supports apixaban as a viable alternative for thromboprophylaxis in NS. Trial Registration: ClinicalTrials.gov: NCT04850378; EudraCT: 2019-001212-29.