Beyond the CHA2DS2VASc: Hypercoagulable States in Anticoagulated AF Patients

Despite the proven efficacy of direct oral anticoagulants (DOACs) in preventing thrombus formation in atrial fibrillation (AF), thrombus formation may rarely occur even with appropriate anticoagulation. We report the case of a 70-year-old woman with a history of AF, initially on warfarin, who underwent percutaneous left atrial appendage closure with a Watchman FLX 27 mm device due to recurrent gastrointestinal bleeding. She subsequently developed multiple unprovoked deep venous thromboses, necessitating the reinitiation of rivaroxaban therapy. She presented to the hospital with complaints of lower abdominal pain. Although the CT abdomen and pelvis was not a dedicated cardiac study, the superior slices incidentally captured the inferior and posterior left atrium, revealing a lobulated soft-tissue density suspicious for thrombus. Labs included INR 1.8, APTT of 40, and D-dimer of 0.62. Transthoracic echocardiography could not visualize thrombus. Transesophageal echocardiography revealed a large mobile thrombus in the superior cavity of LA. The watchman device was well seated with no flow noted across the device. A hypercoagulability workup showed low levels of Protein S antigen at 21. She was placed on warfarin. Follow-up TEE in 3 months showed a decrease in the thrombus size. This case highlights the importance of evaluating an underlying hypercoagulable state when thrombus develops despite DOAC therapy. While DOACs prevent thrombus formation in atrial fibrillation, their failure should not be dismissed as incidental. Clinicians should pursue a hypercoagulability workup, especially when thromboembolic events appear disproportionate to the CHA₂DS₂-VASc score. Early identification of inherited or acquired thrombophilies can guide tailored and effective long-term management.