Etiology of Secondary Iron Overload Secondary iron overload typically occurs in patients who have Hemoglobinopathies (eg, sickle cell disease, thalassemia, sideroblastic anemias) Congenital hemolytic anemias (eg, hemoglobinopathies, hereditary spherocytosis) Myelodysplasia Iron overload results from the following mechanisms: Increased iron absorption Exogenous iron given to treat anemia Repeated blood transfusions (each unit of blood provides about 250 mg of iron; tissue deposition becomes significant when more than about 40 units of blood are transfused) Increased iron absorption in patients with ineffective erythropoiesis may be partly due to the secretion, by erythroid precursors, of erythroferrone (ERFE), which suppresses hepcidin (an inhibitor of iron absorption).