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

Patrick C. Hines, Michael U. Callaghan, Ahmar U. Zaidi, Xiufeng Gao, Ke Liu, Jennell White, Michael Tarasev

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 = 0·015). Optimal cut-off values were established with Cox regression models for FA-WB-Psel [46 cells/mm²; hazard ratio (HR): 2·3; 95% confidence interval (CI):1·4–4·0; P = 0·01] and FA-WB-VCAM (408 cells/mm², HR:1·8; 95% CI: 0·9–3·45; P = 0·01). A combined (FA-WB-Psel and FA-WB-VCAM) multimarker risk score was also significantly (P = 0·0006) correlated with VOC risk that was two-fold higher for intermediate and 5·64-fold higher for high score. The concordance (C)-index for the multimarker score was 0·63 in the six-month period (95% CI: 0·56–0·70), indicating a better ability to distinguish patient risk of VOC, compared to individual biomarkers FA-WB-VCAM (C-index: 0·57; 95% CI: 0·49–0·65) or FA-WB-Psel (C-index: 0·58; 95% CI: 0·53–0·62). 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.

Original languageEnglish
Pages (from-to)1074-1082
Number of pages9
JournalBritish Journal of Haematology
Volume194
Issue number6
DOIs
StatePublished - Sep 2021

Keywords

  • P-selectin
  • biomarker
  • flow adhesion
  • sickle cell disease
  • vascular cell adhesion molecule-1

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