Growth differentiation factor-15 in children and adolescents with thalassemia intermedia: Relation to subclinical atherosclerosis and pulmonary vasculopathy

BackgroundHeart disease is the leading cause of mortality and one of the main causes of morbidity in β-thalassemia. Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-β superfamily, is a marker of ineffective erythropoiesis in several anemias.AimTo determine GDF-15 levels in children and adolescents with TI and the relation to hemolysis, iron overload and cardiovascular complications.MethodsGDF-15 was measured in 35 TI patients without symptoms for heart disease and correlated to echocardiographic parameters and carotid intima media thickness (CIMT).ResultsGDF-15 levels were significantly higher in TI patients compared with controls (p < 0.001). Transfusion dependent patients had higher GDF-15 than non-transfusion dependent patients. TI patients with splenectomy, pulmonary hypertension risk, and heart disease had higher GDF-15 levels than those without. GDF-15 was lower among hydroxyurea-treated patients. Multiple linear regression analysis revealed that transfusion index (p = 0.012), serum ferritin (p < 0.001), tricuspid regurgitant jet velocity (p < 0.001), ejection fraction (p = 0.01) and CIMT (p = 0.007) were independently related to GDF-15. According to ROC curve analysis, the cutoff value of GDF-15 at 1500 pg/mL could differentiate patients with and without heart disease.ConclusionGDF-15 would identify TI patients at increased risk of pulmonary and cardiovascular complications as well as subclinical atherosclerosis.