Real World studies can provide the foundational support necessary for clinicians to effectively manage anticoagulated patients with severe, often life-threatening intracranial and gastrointestinal bleeding. While randomized controlled clinical trials have provided the initial data necessary for appropriate use of reversal agents such as andexanet alfa for Factor Xa associated bleeding, broader studies enrolling thousands of patients, many with significant co-morbidities, are extremely valuable to clinicians. New information regarding the randomized controlled trial ANEXXA-I, which was halted due to andexanet alfa efficacy, provides additional information supporting reversal therapy for severe bleeding.