Research indicates that trauma among patients on anti-factor Xa drugs can produce life-threatening major bleeding in the absence of a reversal agent. Andexanet alfa is a specific reversal agent that acts as a factor Xa decoy to bind molecules that target factor Xa, thus reversing their activity. For a substudy of the ANNEXA-4 trial, patients aged approximately 81, among whom 47% were men and about 87% were taking apixaban or rivaroxaban to prevent blood clots that could lead to strokes due to atrial fibrillation, received an andexanet alfa infusion upon experiencing an adjudicated traumatic intracranial hemorrhage. Among them, 83.9% achieved excellent or good hemostasis within 12 hours of andexanet alfa delivery, with an excellent outcome defined as a 0% to 20% increase from baseline in volume or thickness of the hemorrhage and a good result as a 20% to 35% increase from baseline of the hemorrhage. The 30-day mortality rate among participants was 10.1%. Andexanet alft treatment reduced anti-factor Xa activity by 94.3% in patients on apixaban and by 91.8% in those on rivaroxaban.