Flow adhesion of whole blood to P-selectin: a prognostic biomarker for vaso-occlusive crisis in sickle cell disease

Blood cell adhesion to P-selectin and vascular cell adhesion molecule-1 (VCAM-1) contributes to the pathophysiology of vaso-occlusion crisis (VOC) events in individuals with sickle cell disease (SCD). We evaluated the use of standardized flow adhesion biomarkers in a six-month, 35-subjects longitudinal study (ELIPSIS). Flow adhesion of whole blood on P-selectin (FA-WB-Psel) and VCAM1 (FA-WB-VCAM), and of isolated white blood cells on P-selectin (FA-WBC-Psel) and VCAM-1 (FA-WBC-VCAM) were elevated on VOC days compared with non-VOC days, but only FA-WB-Psel reached statistical significance (P = 0 center dot 015). Optimal cut-off values were established with Cox regression models for FA-WB-Psel [46 cells/mm(2); hazard ratio (HR): 2 center dot 3; 95% confidence interval (CI):1 center dot 4-4 center dot 0; P = 0 center dot 01] and FA-WB-VCAM (408 cells/mm(2), HR:1 center dot 8; 95% CI: 0 center dot 9-3 center dot 45; P = 0 center dot 01). A combined (FA-WB-Psel and FA-WB-VCAM) multimarker risk score was also significantly (P = 0 center dot 0006) correlated with VOC risk that was two-fold higher for intermediate and 5 center dot 64-fold higher for high score. The concordance (C)-index for the multimarker score was 0 center dot 63 in the six-month period (95% CI: 0 center dot 56-0 center dot 70), indicating a better ability to distinguish patient risk of VOC, compared to individual biomarkers FA-WB-VCAM (C-index: 0 center dot 57; 95% CI: 0 center dot 49-0 center dot 65) or FA-WB-Psel (C-index: 0 center dot 58; 95% CI: 0 center dot 53-0 center dot 62). The presented multimarker score can be used to risk-stratify individuals with SCD during their steady state into low, intermediate, and high-risk strata for self-reported VOCs. Such risk stratification could help focus healthcare resources more efficiently to maintiain health, personalize treatment selection to each patient's individual needs, and potentially reduce healthcare costs.