Andexanet-induced Heparin Resistance in Cardiac Surgery - A Rapid Review of Case Reports and Series.

Abstract

Background: Andexanet alfa, a Food and Drug Administration (FDA)-approved antidote for apixaban and rivaroxaban, is used to manage life-threatening or uncontrolled bleeding. In patients undergoing cardiopulmonary bypass (CPB), prior exposure to andexanet can cause severe heparin resistance, necessitating effective mitigation strategies. A comprehensive review of such strategies remains lacking.

Objective: To systematically review and characterize cases of andexanet-induced heparin resistance in patients undergoing CPB and to evaluate management strategies.

Methods: A systematic search was conducted across multiple databases via the Ovid interface, Cochrane Central Register of Controlled Trials, and the FDA Adverse Event Reporting System. Quality appraisal was performed using a validated instrument for case reports and series describing drug-induced adverse events.

Results: Fourteen discrete patient cases met inclusion criteria. Post-andexanet administration, the mean initial activated clotting time (ACT) was 199.5 seconds, falling short of a target of >400 seconds despite additional heparin dosing (mean total: 1,123 U/kg). 35.7% of all cases involved thrombus formation in the reservoir; two of which required a circuit replacement. Antithrombin (AT) concentrate was administered to 75% of those received an adjunct therapy. A prophylactic AT use (mean, 49.9 IU/kg) resulted in an ACT over 400 seconds, while its effects in low-dose after the occurrence of thrombosis varied on ACT values. Nafamostat mesylate was used in some cases reported from Japan CONCLUSIONS: Heparin resistance following andexanet exposure poses significant procoagulant risk during CPB. Preemptive high-dose antithrombin therapy may improve ACT values. Further studies are needed to understand the mechanisms and optimize management of this condition.