Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature.

Brain metastases (BMs) are the most common intracranial malignancy with poor prognosis. Patients with intracranial tumors are at greater risk for thrombotic complications and intracranial hemorrhage. Rivaroxaban is a potent oral anticoagulant with the high selectivity of direct factor Xa inhibition. The incidence and severity of rivaroxaban-triggered intratumoral hemorrhage (ITH) in patients with BMs remain unknown. A 57-year-old woman was diagnosed with multiple lung, bone, and BMs from unknown primary cancer origin, and refused any invasive procedures to confirm tumor pathology. However, this patient had a relatively favorable outcome after treating with cabozantinib, an inhibitor of multiple tyrosine kinases. The patient survived over 2 years and developed deep vein thrombosis of right lower limb. Oral rivaroxaban was prescribed, and the multifocal catastrophic ITH was encountered after 1 week. The last head computed tomography imaging revealed a rare but typical image of diffuse hemorrhagic metastases. Hemorrhagic-prone BMs, therapeutic rivaroxaban, and cabozantinib treatment increase risks to develop ITH. In this case rivaroxaban was the trigger to this terminal event. This case is a miserable lesson and keeps reminding us to stay vigilant in clinical practice even when there is a potential benefit for anticoagulation in such population.