Growth differentiation factor-15 in young sickle cell disease patients: Relation to hemolysis, iron overload and vascular complications

BackgroundHigh expression of growth differentiation factor-15 (GDF-15) contributes to pathological iron overload in thalassemia. Sickle cell syndromes are characterized by increased levels of erythropoiesis, although the primary defect involves the destruction of mature erythrocytes.AimTo determine serum GDF-15 in 35 children and adolescents with sickle cell disease (SCD) compared to 35 healthy controls and assess its relation to markers of hemolysis, iron overload and vascular complications.MethodsGDF-15 was measured and correlated to genotype, frequency of sickling crises, hydroxyurea therapy and serum ferritin.ResultsGDF-15 levels were increased in SCD patients whether sickle cell anemia or sickle β° thalassemia compared with controls (p < 0.001) with no significant difference between patients' groups. GDF-15 was significantly higher in patients who had serum ferritin ≥ 2500 μg/L, previous cerebral stroke, and splenectomy. GDF-15 was not significantly related to frequency of sickling crises, pulmonary hypertension, or hydroxyurea therapy. On regression analysis, transfusion index, lactate dehydrogenase and serum ferritin were independently related to GDF-15.ConclusionIncreased GDF-15 in SCD reflects the importance of ineffective erythropoiesis in the pathophysiology and severity of anemia in SCD. GDF-15 levels are related to hemolysis and iron overload and may provide utility for identifying patients at increased risk of thrombotic events.