VEXAS cohort links endothelial dysfunction and VWF abnormalities to hypercoagulability

An observational study published in Blood examined mechanisms potentially underlying the high thrombotic risk associated with VEXAS syndrome. Researchers assessed a cohort of 40 patients referred to the National Institutes of Health with defined pathological UBA1 sequence variants, comparing plasma markers of endothelial activation and coagulation with those of age-matched controls.

Twenty-one patients (52.5%) had experienced thrombotic events. Plasma von Willebrand factor (VWF) and factor VIII activity levels were increased compared with controls. VWF propeptide and angiopoietin II levels were significantly elevated, consistent with endothelial activation and Weibel–Palade body exocytosis. Patients also showed accumulation of high-molecular-weight VWF multimers and significantly higher soluble vascular cell adhesion molecule-1 and soluble thrombomodulin levels, supporting ongoing endothelial dysfunction. Thrombin generation and activated protein C resistance were also significantly increased.

These findings implicate endothelial dysfunction and quantitative and qualitative VWF abnormalities in VEXAS-associated hypercoagulability, but do not establish that targeting these pathways prevents thrombosis. The available abstract does not report control-group size, numerical biomarker differences, or associations between individual markers and thrombotic events. The referred cohort and small sample warrant caution in generalizing the findings. Further studies are needed to evaluate interventions targeting endothelial cells or the VWF–ADAMTS13 axis.