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

Thromb Res. 2013;132(6):712-7. doi: 10.1016/j.thromres.2013.10.006. Epub 2013 Oct 12.


In adult patients with sickle cell disease two distinct subphenotypes have previously been defined: patients with the viscosity-vaso-occlusion subphenotype (VVO) suffer mainly from vaso-occlusive pain crises and have a relatively high hemoglobin concentration. Patients classified as the hemolysis-endothelial dysfunction subphenotype (HED) suffer from stroke and pulmonary hypertension and have an elevated concentration of lactate dehydrogenase. However, this classification is not possible in children due to low rates of complications. We used laboratory markers to classify children into the two subphenotypes, and measured vWF and vWF propeptide as markers of endothelial dysfunction. We included 106 children with sickle cell disease (mean age 8.7years), 74 (70%) with HbSS/HbSβ° genotype and 32 (30%) with HbSC/HbSβ(+) genotype. vWF and vWF propeptide were significantly elevated in patients with sickle cell disease; this was more pronounced in patients with the HbSS/HbSβ° genotype. Patients with the HED subphenotype had higher levels of vWF propeptide, and a trend towards higher levels of vWF compared to those with the VVO subphenotype. We demonstrated that even young children in a stable clinical condition show signs of persistent endothelial dysfunction. A prospective study should demonstrate whether elevated levels of vWF and its propeptide are associated with an increased risk of complications specific for the HED subphenotype.

Keywords: CAR; Central African Republic haplotype; ELISA; Endothelial dysfunction; F1+2; HED; Hb; HbF; LDH; MRA; MRI; NO; Pediatric hematology/oncology; SCD; SCI; Sickle cell disease; TAT; VVO; enzyme-linked immunosorbent assay; hemoglobin; hemoglobin F percentage; hemolysis-endothelial dysfunction subphenotype; lactate dehydrogenase; magnetic resonance angiography; magnetic resonance imaging; nitric oxide; prothrombin fragment 1 and 2; sickle cell disease; silent cerebral infarcts; thrombin-antithrombin complex; vWF; viscosity-vaso-occlusion subphenotype; von Willebrand factor; von Willebrand factor propeptide.

MeSH terms

  • Adolescent
  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / classification*
  • Anemia, Sickle Cell / physiopathology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Disease Progression
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Male
  • Phenotype
  • Risk Assessment
  • Stroke / blood
  • Stroke / physiopathology
  • von Willebrand Factor / metabolism


  • von Willebrand Factor