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Combined Antithrombin and Heparin Supplementation to Blood for Restoring Heparin Responsiveness After Andexanet Alfa Exposure: An In Vitro Model.


ABSTRACT:

Background

Andexanet alfa, a Gla-domainless mutant factor Xa (GDXa), reverses oral FXa inhibitors but can cause severe heparin resistance during cardiopulmonary bypass (CPB). Antithrombin (AT) supplementation may mitigate this effect, though dosing evidence is limited.

Methods

We evaluated in vitro the effectiveness of combined heparin and AT in restoring heparin responsiveness after andexanet exposure. Whole blood and platelet-poor plasma from surgical patients on CPB were spiked with andexanet at target concentrations of 2.9 and 4 µM, respectively. Heparin responsiveness was assessed using kaolin-activated clotting time (ACT), ellagic acid-activated thromboelastometry (INTEM), and thrombin generation (TG) assays. Heparin alone or with AT (0.8-3.1 µM in whole blood; 1.1-4.4

SUBMITTER: Butt AL 

PROVIDER: S-EPMC12857465 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature