VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described autoinflammatory syndrome characterized by diffuse inflammatory manifestations, predisposition to hematological malignancy, and an association with a high rate of thrombosis. VEXAS is attributed to somatic mutations in the UBA1 gene in hematopoietic stem and progenitor cells with myeloid restriction in mature forms. The rate of thrombosis in VEXAS patients is approximately 40% in all reported cases to date. Venous thromboembolism predominates thrombotic events in VEXAS. These are classified as unprovoked in etiology, although systemic and vascular inflammation are implicated. Here, we review the clinical and laboratory characteristics in VEXAS that provide insight into the possible mechanisms leading to thrombosis. We present knowledge gaps in the mechanisms and management of VEXAS-associated thromboinflammation and propose areas for future investigation in the field.
Keywords: Antiphospholipid syndrome; Autoimmune; Coagulation; Inflammation; Innate immune; Lupus anticoagulant; Monocyte; Myelodysplastic syndrome; Neutrophil; Thrombosis; Ubiquitin; VEXAS.
Published by Elsevier Inc.