Decreased synthesis of transferrin in these cases may also contribute to development of NTBI and LIP, while transfusions in early stages lead to macrophage iron overload and increased serum ferritin with normal TSAT; with increasing transfusion load, iron accumulation overwhelms the capacity of the macrophages, leading to increased TSAT and, thus, parenchymal iron overload [61]. This evidence concerns the gene TF and medical procedure.