4 Pathophysiology of thalassaemia

Abstract

Most of the major clinical manifestations of the β-thalassaemias can be related to the deleterious effects of imbalanced globin chain synthesis on erythroid maturation and red cell survival. The destruction of red cell progenitors and their progeny results from an extremely complex series of mechanisms all related to the presence of excess α-globin chain production. These include mechanical damage, interference with cell division and oxidative destruction of both organelles and components of the red cell membrane. The unequal distribution of γ-globin chains between different precursors, and the intense selection of those with relatively higher levels of γ chain production, lead to an extremely heterogeneous cell population in the peripheral blood. Iron overload, due to increased gastrointestinal absorption and blood transfusion is the major cause of tissue damage, morbidity and death.