Pathophysiology of beta thalassaemia

In beta thalassemia, unbalanced alpha globin chain synthesis results in severely rheologically compromised erythrocytes with premature destruction in the peripheral circulation and ineffective erythropoiesis within the bone marrow and in extramedullary sites. In nontransfused beta thalassemia patients, erythropoiesis,anemia and hypoxia down-regulate hepcidin, the master regulator of iron homeostasis. Hepcidin deficiency in turn allows excessive duodenal iron absorption and development of systemic iron overload. In regularly transfused patients iron overload is mostly due to red cell breakdown. When the iron binding capacity of transferrin is saturated, iron can appear in the serum in a free form, called Non-Transferrin-Bound Iron, a powerful catalyst for the formation of free radicals, capable of causing oxidative stress and damage to mitochondria, lysosomes, lipid membranes, proteins, and DNA. Apart from the iron overload-related complications, other pathological conditions such as bone disease, gallstones and thromboembolic events occur in a relevant proportion of subjects with thalassemia.