VEXAS Syndrome and Thrombosis: Findings of Inflammation, Hypercoagulability, and Endothelial Dysfunction

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a novel autoinflammatory syndrome due to a ubiquitin like modifier activating enzyme 1 (UBA1) somatic mutation, recently discovered in 2020.[1] This mutation affects the major E1 enzyme that initiates ubiquitin conjugation of cellular proteins meant for degradation by proteasomes, where decreased ubiquitination causes accumulation of prominent intracellular vacuoles seen in myeloid and erythroid precursors in the bone marrow.[2] This autoinflammatory disease has a significant hematologic malignancy and thrombotic burden, with an increased incidence of venous thromboembolism (VTE) (36.4%), where deep vein thrombosis (DVT) is more common than pulmonary embolism (PE), with a lower incidence of arterial thrombosis (1.6%).[3] However, limited information is available on the potential mechanisms of thrombosis in patients with VEXAS syndrome. We describe two male patients with VEXAS syndrome diagnosed in Singapore and performed biomarkers evaluating the hemostatic, inflammatory, and endothelial function.