Pharmacovigilance study of spinal epidural hematoma reports associated with direct oral anticoagulants and warfarin

BACKGROUND: Spontaneous spinal epidural hematoma (SEH) is a rare but potentially catastrophic condition that may be worsened by anticoagulation. We evaluated reporting patterns and signal strength of SEH associated with warfarin and DOACs using pharmacovigilance database analysis. METHODS: A retrospective disproportionality analysis was conducted using the FDA Adverse Event Reporting System (FAERS) from Q4/2003 to Q2/2025. Reports of SEH associated with warfarin, rivaroxaban, apixaban, and dabigatran were analyzed. Signal detection employed Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and chi-squared analysis with Yates' correction. A signal was significant if n > 3, χ2 > 4, and PRR > 2. RESULTS: A total of 143 SEH reports were identified. Warfarin accounted for 83 cases, rivaroxaban 28, apixaban 25, and dabigatran 7. All demonstrated significant disproportionality signals. Warfarin showed the strongest signal (ROR 29.2, 95% CI 22.9-37.1), followed by rivaroxaban (ROR 8.09), dabigatran (ROR 5.75), and apixaban (ROR 4.78). Warfarin patients were younger (mean 62 years) than DOAC users (75-76 years). Mortality occurred in 9 warfarin and 8 rivaroxaban cases. Atrial fibrillation was the most frequent indication for anti-coagulation. CONCLUSIONS: This pharmacovigilance study identified disproportionate reporting signals for spinal epidural hematoma across warfarin and DOACs, with stronger signals observed for warfarin and rivaroxaban. Given the inherent limitations of spontaneous reporting databases, these findings should be interpreted as hypothesis-generating rather than causal. Further controlled studies are needed to determine true incidence and comparative risk.