GDF15 as a Marker of Ineffective Erythropoiesis and Erythroid Expansion in Thalassemia: a Clinical Perspective

BACKGROUND: Ineffective erythropoiesis is a hallmark of thalassemia syndromes. Growth differentiation factors, such as GDF15, play a crucial yet not fully understood role. METHODS: Serum GDF15 levels were measured by ELISA in 486 individuals (362 thalassemia patients, 53 β-trait carriers, and 71 healthy subjects) and analyzed alongside biochemical and clinical parameters. RESULTS: GDF15 levels were elevated in transfusion-dependent (TD) β-thalassemia (26-fold), non-transfusion-dependent (NTD) β-thalassemia (6-fold), and β-thalassemia carriers (2-fold) compared to healthy controls. Moreover, GDF15 levels were elevated in α-thalassemia patients (2-fold) compared to carriers. In TD β-thalassemia, GDF15 correlated inversely with hemoglobin and positively with erythropoietin. GDF15 also correlated with iron metabolism markers. Longitudinal analysis in a TD patient subgroup showed dynamic GDF15 changes post-transfusion, reflecting erythropoietic activity. Furthermore, GDF15 levels correlated with transfusion intervals, particularly in splenectomized patients. CONCLUSIONS: GDF15 represents a promising biomarker for assessing thalassemia severity, monitoring treatment responses, and guiding therapies.