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

Abstract

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.

Adhesion to VCAM1 and P-selectin Predict Time-to-Resolution (TTR) of Vaso-Occlusive Crisis

“…No correlation was observed with FA-WB-VCAM measured during VOC. Previous reports suggested that FA-WB-VCAM at clinical baseline as one of the determinants of the overall disease severity [13], with such elevated severity potentially contributing to P-selectin-driven onset of VOC.…”

“…No correlation was observed with FA-WB-VCAM measured during VOC. Previous reports suggested that FA-WB-VCAM at clinical baseline as one of the determinants of the overall disease severity [13], with such elevated severity potentially contributing to P-selectin-driven onset of VOC. Additionally, increased VCAM-1/VLA-4 interactions may lengthen TTR because more adhesive sickle RBCs may become trapped in post capillary venules, further contributing to VOC events.…”

“…High levels of VLA-4 and VCAM-1 have been associated with vaso-occlusive adhesive events and severe disease phenotypes, and with a response to SCD-modifying therapy [21][22][23][24][25][26]. Elevated VLA-4/ VCAM-1 binding at baseline strongly correlates with SCD severity, providing an on-going, and relatively slow changing background for RBC-endothelial adhesive interactions [13].…”

“…We also demonstrated that baseline FF-WB-VCAM levels stratifies SCD patients based on disease severity (high or moderate/normal adhesion phenotype). In a 2-year prospective study, the high adhesion cohort experienced significantly more VOCs when compared to the normal/moderate adhesion phenotype [13]. In this study, we investigated additional relationships between FF-WB-VCAM and FF-WB-Psel, along with other chemical biomarkers, and the time to the resolution (TTR) from VOC in SCD subjects.…”

Computing Sickle Erythrocyte Health Index Based on Quantitative Phase Imaging and Machine Learning

“…15,16 While most of these works have been conducted using blood samples collected at one-time point, some have utilized longitudinal studies to better understand the temporal nature of sickle cell disease on the time scale of weeks and months. 17 Our work is not the rst to use QPI to image sickle cell erythrocytes. Previous studies have used QPI to explore a variety of different research questions.…”