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

High 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. To 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. GDF-15 was measured and correlated to genotype, frequency of sickling crises, hydroxyurea therapy and serum ferritin. GDF-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. Increased 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.