Andexanet alfa for the reversal of the low-molecular-weight heparin enoxaparin

作者：Thijs F. van Haaps, Alexander P. Benz, Lizhen Xu, Saskia Middeldorp, John W. Eikelboom, Truman J. Milling, Mark Crowther, Lisa Holer, Stephan Nolan, Per Ladenvall, Genmin Lu, Michiel Coppens · 发表于：Research and Practice in Thrombosis and Haemostasis · 年份：2025 · DOI：10.1016/j.rpth.2025.103191 · 被引用次数：2 · 研究领域：Venous Thromboembolism Diagnosis and Management、Blood Coagulation and Thrombosis Mechanisms、Atrial Fibrillation Management and Outcomes

Background: Andexanet alfa (andexanet) is the only approved reversal agent for patients with acute major bleeding during apixaban or rivaroxaban treatment. Its mechanism suggests it may also reverse the effects of low-molecular-weight heparin. Aim: To evaluate the effects of andexanet in healthy volunteers and in patients with acute major bleeding on enoxaparin. Methods: In the first study, healthy volunteers received enoxaparin 1 mg/kg twice daily for ≥3 doses and were randomized to receive either andexanet or placebo in high- or low-dose regimens, given 3 hours (high dose) or 8 hours (low dose) after the last dose. In the second study (Andexanet Alfa, a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors 4), dosing depended on timing and amount of last enoxaparin dose: high dose if > 40 mg or <8 hours since last dose (or unknown), low dose if ≤ 40 mg or ≥8 hours. The high dose consisted of an 800 mg bolus followed by 960 mg >2 hours, while low dose consisted of a 400 mg bolus followed by 480 mg >2 hours. The primary outcome was change in anti-Xa activity. Hemostatic efficacy was assessed in patients with confirmed bleeding and baseline anti-Xa ≥ 0.25 IU/mL. Results: In the first study, 24 volunteers received andexanet (12 at a high dose and 12 at a low dose), and 7 received a placebo. Median anti-Xa activity decreased by 83% (0.92-0.17 IU/mL) in the high-dose cohort, and by 73% (0.78-0.22 IU/mL) in the low-dose cohort. In the second study, 22 patients received and...