Apixaban Concentrations and Effects on Coagulation in Patients With Nephrotic Syndrome

Area of Science:

• Pharmacology
• Nephrology
• Hematology

Background:

• Venous thromboembolism (VTE) is a significant complication in nephrotic syndrome (NS).
• Current guidelines recommend warfarin or low molecular weight heparin (LMWH) for VTE prophylaxis in NS.
• Limited data exist on the use of direct oral anticoagulants (DOACs) in NS patients.

Purpose of the Study:

• To evaluate the steady-state concentrations and anticoagulant effects of standard-dose apixaban in patients with NS.
• To compare apixaban's efficacy with dalteparin in suppressing thrombin generation in NS.

Main Methods:

• An open-label, single-arm clinical trial involving adult patients with NS and healthy controls.
• Patients with NS received dalteparin followed by apixaban 5 mg twice daily.
• Assessed apixaban steady-state plasma concentrations and thrombin generation markers.

Main Results:

• Mean steady-state apixaban levels were lower in NS patients (35 μg/L) compared to healthy individuals (51 μg/L) (P=0.02).
• Endogenous thrombin potential was comparable between groups at steady-state (P=0.19).
• Apixaban demonstrated greater suppression of in vivo thrombin generation markers than dalteparin in NS patients.

Conclusions:

• Patients with NS exhibit lower apixaban concentrations but achieve comparable anticoagulant effects to healthy individuals.
• Apixaban effectively suppresses thrombin generation, outperforming dalteparin in NS.
• Apixaban presents a potential alternative for thromboprophylaxis in nephrotic syndrome.