To reverse or not to reverse: Direct oral anticoagulants in mild traumatic brain injury

The growing usage of direct oral anticoagulants (DOACs) has brought into question the need for pharmacologic reversal in patients who develop traumatic brain injuries (TBIs). While there are specific benefits in reversal for TBI patients on warfarin, the impact has not been clearly shown in DOAC populations. This study evaluated radiographic and clinical outcomes among patients with isolated mild TBIs to determine whether DOAC usage or its reversal confers measurable differences in early outcomes.

We conducted a retrospective review of adults (18 to 99 y) with isolated mild TBI (Glasgow Coma Scale: 13 to 15) after ground-level falls at a Level I trauma center from 2016 to 2024. The primary outcome was radiographic hemorrhage progression, defined as >2-mm increase in hemorrhage or need for >2 head computed tomographies within 24 hours. Secondary outcomes included Glasgow Coma Scale decline, intensive care unit length of stay, neurosurgical intervention, thromboembolic events, disposition, and inpatient mortality. Multivariable logistic regression and propensity score matching were used to evaluate associations between DOAC usage, reversal therapy, and outcomes.

Among 273 patients, 96 (35%) were taking a DOAC, and of these, 41 received four-factor prothrombin complex concentrate and 18 received andexanet alfa. DOAC patients demonstrated similar rates of radiographic progression, intensive care unit length of stay, and discharge disposition compared with non-DOAC patients. In multivariate analysis, DOAC usage was not associated with increased radiographic progression, measured by subdural hemorrhage growth (47.5% vs. 44.8%; p = 0.70) or increased need for >2 computed tomography scans (49.1% vs. 48.9%, p = 1.00). Among DOAC users, reversal was also not associated with improved radiographic progression or secondary outcomes. No significant outcome differences were observed between reversal with four-factor prothrombin complex concentrate and andexanet alfa.

In isolated mild TBI after ground-level falls, DOAC usage was not associated with worsened clinical outcomes or increased radiographic progression. Pharmacologic reversal offered no measurable benefit. These findings support selective reversal in stable mild TBI. ( J Trauma Acute Care Surg . 2026;00: 000-000 Copyright © 2026 Wolters Kluwer Health, LLC. All rights reserved.).

Therapeutic/Care Management; Level III.