Beta Thalassaemia Major

Beta thalassaemia is a serious haematological disorder where the formation of beta chains is impaired. Haemoglobinopathies are where the haemoglobin molecule which is formed is abnormal. Thalassaemias are where the molecule is made with normal chains but at a reduced rate. Thalasaemias therefore include hundreds of different mutations, all of which impair the rate of haemoglobin formation. There are even thalassaemic haemoglobinopathies (such as Hb E) where both the rate and molecule are abnormal. When the beta chain is made too slowly, you get a pattern of abnormal and inadequate haemoglobinisation. This causes anaemia, and in turn drives more ineffective erythropoiesis. 

Morphologically, there is a hypochromic, microcytic anaemia. The cells that are produced are usually abnormal, showing abnormal haemoglobinisation. In beta thalassaemia there are nucleated red blood cells - this is a useful distinction as alpha thalassaemia doesn't cause these. We see frequent pappenheimer bodies, which are inclusions of iron and ferritin. There is basophillic stippling where the inclusions are coarser and larger - these are leftover RNA and ribosomes which were not cleared before the cells were pushed into circulation. The overall effects can all be explained by two issues - not enough haemoglobin (causing the hypochromia and abnormal haemoglobinisation), and the erythropoeitic drive which causes the nRBC, pappenheimer bodies and basophillic stippling. 

We classify thalassaemias clinically normally - as thalassaemia minor where the condition isn't normally a problem, thal intermedia where the patient may need transfusion in times of physiological stress, and thal major where patients need regular transfusions. We blur the lines regularly between thal minor and thal trait - minor is a clinical name, trait refers to the genetics. The reason is that the majority of thal minors are thal trait, where there is one normal and one abnormal beta gene.