Direct oral anticoagulants (DOACs) are used for many conditions where anticoagulation is needed such as non-valvular atrial fibrillation, deep vein thrombosis (DVT) and pulmonary embolism (PE). These novel agents have become popular since they do not require monitoring of therapeutic levels and there is a lower risk of certain bleeding complications when compared to warfarin. However, the efficacy and side effect profile of these agents have not been widely studied in certain patient cohorts, namely cancer patients and patients on immunomodulators or hormone analogs. We present a case of a patient with a history of malignancy and autoimmune disease who developed pericardial and pleural effusions shortly after initiating apixaban for treatment of a PE. In addition, we aim to increase awareness of the role that the newly available reversal agents for anticoagulants would offer in the acute management of hemorrhagic pericardial and pleural effusions caused by DOACs in patients with and without malignancy.