Longitudinal assessment of adhesion to vascular cell adhesion molecule‐1 at steady state and during vaso‐occlusive crises in sickle cell disease

Sickle cell disease (SCD) is characterized by frequent and unpredictable vaso‐occlusive crises (VOCs). Sickle erythrocytes (SSRBCs) contribute to VOCs by participating in a series of adhesive events with blood cells and the vascular endothelium. Adhesion assays have been used to evaluate the relationship between SSRBC adhesion and SCD severity. We developed a standardized, clinical flow adhesion assay of whole blood to vascular cell adhesion molecule (FA‐WB‐VCAM). The objective of this study was to assess the variability and clinical predictive value of FA‐WB‐VCAM in a six‐month longitudinal, observational study (ELIPSIS) in SCD subjects during at‐home, steady‐state and self‐reported VOCs, and following VOC resolution. We observed a strong relationship between FA‐WB‐VCAM and SCD severity. Adhesion indices were significantly lower in SCD subjects on hydroxycarbamide and increased during VOCs; at‐home VOCs had significantly higher FA‐WB‐VCAM than steady‐state and contact VOCs. SCD subjects with a high frequency of self‐reported VOCs had a pro‐adhesive phenotype at steady state and were stratified into a high‐adhesive phenotype cohort; two years prospectively we observed a higher frequency of VOCs in the high‐adhesion cohort. This study supports stratifying SCD subjects based on steady‐state FA‐WB‐VCAM and suggests that FA‐WB‐VCAM may be a plausible surrogate end‐point for SCD severity.