The Growth Differentiation Factor-15 (GDF-15) levels are increased in patients with compound heterozygous sickle cell and beta-thalassemia (HbS/βthal), correlate with markers of hemolysis, iron burden, coagulation, endothelial dysfunction and pulmonary hypertension

Abstract

The clinical manifestations of Sickle Cell Disease (SCD) include episodes of vascular occlusion, chronic hemolytic anemia and frequent infections. GDF-15, a multifactorial cytokine, is a member of the transforming growth factor- superfamily. Expression of the GDF-15 gene in cardiomyocytes, vascular smooth muscle cells, and endothelial cells is strongly upregulated in response to oxidative stress, inflammation and tissue injury, while high levels of serum GDF-15 associate with ineffective erythropoiesis and may reflect a certain type of bone marrow stress or erythroblast apoptosis. In this context we aimed to evaluate GDF-15 levels in 89 patients with HbS/βthal at steady phase and in 20 apparently healthy individuals, and correlate with clinical features of the disease and markers of hemolysis, iron burden, inflammation, coagulation and endothelial dysfunction. We found that: GDF-15 levels were elevated in patients with HbS/βthal compared to controls (1980.7 ± 159.8 vs 665.4 ± 50.9 pg/mL, p < 0.0001) and correlated significantly with LDH (p < 0.001), Hepcidin-25/Ferritin molar ratio (p = 0.002), vWF:antigen (p < 0.05), HbA% (p < 0.001) and Mean Pulmonary Artery Pressure (p < 0.001). These findings demonstrate for first time an important multifactorial role of GDF-15 in patients with HbS/βthal, however, prior to its clinical usefulness, this biomarker must undergo through rigorous validation in multiple cohorts.