Markers of endothelial dysfunction differ between subphenotypes in children with sickle cell disease

Area of Science:

• Hematology
• Pediatric Medicine
• Vascular Biology

Background:

• Sickle cell disease (SCD) presents distinct subphenotypes in adults: viscosity-vaso-occlusion (VVO) and hemolysis-endothelial dysfunction (HED).
• Current classification methods are not applicable to children due to lower complication rates.
• Endothelial dysfunction is a key factor in SCD pathophysiology.

Purpose of the Study:

• To adapt the adult SCD subphenotype classification for use in children.
• To investigate the utility of von Willebrand factor (vWF) and vWF propeptide as biomarkers for endothelial dysfunction in pediatric SCD.
• To assess for early signs of endothelial dysfunction in children with SCD.

Main Methods:

• Laboratory markers, including vWF and vWF propeptide, were measured in 106 children with SCD (mean age 8.7 years).
• Patients were classified into VVO and HED subphenotypes based on these laboratory markers.
• Genotypes (HbSS/HbSβ°, HbSC/HbSβ(+)) were considered in the analysis.

Main Results:

• vWF and vWF propeptide levels were significantly elevated in children with SCD, particularly in those with HbSS/HbSβ° genotype.
• Patients classified with the HED subphenotype exhibited higher vWF propeptide levels and a trend towards higher vWF levels compared to the VVO subphenotype.
• Persistent endothelial dysfunction markers were evident even in children in stable clinical condition.

Conclusions:

• Laboratory markers, specifically vWF and vWF propeptide, can be used to classify pediatric SCD into VVO and HED subphenotypes.
• Children with SCD demonstrate persistent endothelial dysfunction early in life, irrespective of clinical stability.
• Elevated vWF and vWF propeptide may serve as predictive markers for HED-specific complications in pediatric SCD, warranting further prospective investigation.