Low Risk of Traumatic Intracranial Hematoma Expansion with Factor Xa Inhibitors without Andexanet Reversal

Abstract

Andexanet alfa, a novel anticoagulation reversal agent for factor Xa inhibitors, was recently approved. Traumatic intracranial hemorrhage presents a prime target for this drug. The Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors study established the efficacy of andexanet alfa in reversing factor Xa inhibitors. However, the association between anticoagulation reversal and traumatic intracranial hemorrhage progression is not well understood. The objective of this study was to determine progression rates of patients with traumatic intracranial hemorrhage on factor Xa inhibitors prior to hospitalization who were managed without the use of andexanet alfa. A retrospective cohort study was performed between 2016 and 2019 at a single institution. An institutional traumatic brain injury (TBI) registry was queried. Patients with recorded use of apixaban or rivaroxaban <18 hours before injury were included. The primary study outcome was <35% increase in hemorrhage volume or thickness on repeated head computed tomography (CT) scans. We identified 25 patients meeting the inclusion criteria. Two patients were excluded because of a lack of necessary CT data. Twelve patients (52%) were receiving apixaban, and 11 were (48%) on rivaroxaban. On admission CT scan, 14 patients had subdural hematoma, 6 had traumatic intraparenchymal hemorrhage, and 3 had subarachnoid hemorrhage. Anticoagulation reversal was attempted in 17 patients (74%), primarily using 4-factor prothrombin complex concentrate. Twenty patients (87%) were adjudicated as having excellent or good hemostasis on repeat imaging. Our results indicate that patients on factor Xa inhibitors with complicated mild TBI have a similar intracranial hemorrhage progression rate to patients who are not anticoagulated or anticoagulated with a reversible agent. The hemostatic outcomes in our cohort were similar to those reported after andexanetalfa administration.