PlGF and sFlt-1 levels in patients with non-transfusion-dependent thalassemia: Correlations with markers of iron burden and endothelial dysfunction

Eur J Haematol. 2018 Jun;100(6):630-635. doi: 10.1111/ejh.13061. Epub 2018 Apr 25.

Abstract

Background: Levels of the angiogenic cytokines placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1) and the angiogenic balance, expressed by sFlt-1/PlGF ratio, are perturbed in sickle-cell disease and iron overload, but they have not been evaluated in non-transfusion-dependent thalassemia (NTDT).

Patients and methods: We measured levels of PlGF, sFlt-1 and vWF:antigen in patients with NTDT of beta-thalassemia genotype, and correlated them with erythrocytic indices and markers of iron overload, inflammation, and tissue hypoxia. Thirty-four NTDT patients with mean hemoglobin level of 8.4 g/dL were included in the study along with 20 apparently healthy individuals who served as controls.

Results: Ferritin, LDH, and hs-CRP were higher in patients as compared to controls. We found significant differences between patients and controls in regard to levels of PlGF (52.2 vs 17.2 pg/mL, P < .001), sFlt-1/PlGF (2 vs 4.7, P < .001), and vWF:antigen (88 vs 77.1 IU/dL, P < .01). There was a strong correlation of ferritin with PlGF (r = .653, P < .001) and with vWF:antigen (r = .503, P = .003).

Conclusions: In this study, we demonstrated an association between increased PlGF and iron overload and the degree of tissue hypoxia in patients with NTDT. High vWF:antigen expressing endothelial damage may be associated with specific NTDT comorbidities.

Keywords: angiogenesis; endothelial dysfunction; inflammation; iron burden; non-transfusion-dependent thalassemia.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • Endothelium, Vascular
  • Female
  • Humans
  • Iron / metabolism
  • Male
  • Membrane Proteins / blood*
  • Middle Aged
  • Sensitivity and Specificity
  • Thalassemia / blood
  • Thalassemia / diagnosis
  • Thalassemia / metabolism*
  • Thalassemia / therapy
  • Vascular Endothelial Growth Factor Receptor-1 / blood*
  • Young Adult

Substances

  • Biomarkers
  • Membrane Proteins
  • PIGF protein, human
  • Iron
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1