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

Abstract

SummarySickle 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.