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), preoperative exposure to andexanet can cause severe heparin resistance, necessitating effective mitigation strategies. A comprehensive review of such strategies remains lacking.

Objectives

This study aimed 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. After 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, 1123 U/kg). Moreover, 35.7% of all cases involved thrombus formation in the reservoir, 2 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.

Conclusion

Heparin resistance following andexanet exposure poses significant procoagulant risk during CPB. Pre-emptive high-dose AT therapy may improve ACT values. Further studies are needed to understand the mechanisms and optimize management of this condition.