Clinical features

Beta-Thalassaemia major

Beta-Thalassaemia major causes severe anaemia in babies within the first year of life. The baby feeds poorly, fails to thrive and is prone to recurrent infections. Without treatment the infant develops various complications including jaundice, gallstones, gout and leg ulcers. The spleen becomes very enlarged as the abnormal haemolysed red blood cells are removed from the circulation. Abnormal red cells pool in the enlarged spleen exacerbating the anaemia.

The bones of the head and face become enlarged and deformed causing an abnormal appearance resulting in a typical “chipmunk facies” appearance. This occurs because the bone marrow, the site of red blood cell production, becomes hyperactive in an attempt to produce sufficient red cells to overcome the effects of the profound anaemia. Deformities of the skull lead to abnormal development of the teeth, sinuses and ears. Other bones in the body may be osteoporotic (thin) and if there are repeated fractures may become deformed due to improper healing. Growth of the limbs and trunk is impaired and the bones tend to fracture easily. Normal puberty is delayed.

Children, who are successfully and intensively treated, grow and develop relatively normally up to puberty and into early adulthood. The cornerstone of treatment of severe anaemia is regular blood transfusions. Children usually cope well in-between transfusions. Adults may be unwell in the week before their regular transfusion. This is because the haemoglobin level drops rapidly after the transfusion and it becomes progressively harder, with age, to compensate for this. Severe fatigue in the pre-treatment week is the main problem. Adults aged 20 and over with Thalassaemia commonly have cardiac or respiratory problems that exacerbate feelings of fatigue and symptoms of anaemia such as breathlessness. They may not for example be able to get up the stairs in the week before transfusion. Regular transfusions lead to an excess of iron in the body – a condition known as iron overload or haemosiderosis. The body absorbs extra iron from the gut as a response to the persistent anaemic state in Thalassaemia, and this adds to the iron overload.

Iron overload is one of the key complications of Thalassaemia treatment and a major cause of disability in the condition. Iron builds up in the tissues and has toxic effects on cells. Cell damage eventually impairs organ function, the conditions this causes are listed below:

• Diabetes mellitus is one of the early effects, often affecting people in their 20s.
• Liver damage leads to cirrhosis and liver failure
• Heart muscle damage leads to arrhythmias - a common cause of sudden death in Thalassaemia
• Heart failure
• Enlarged heart (cardiomyopathy)
• Delayed sexual maturation (termed hypogonadotrophic hypogonadism in the medical evidence),
• Delayed growth and weakened bones (osteoporosis), severe pain from arthritis particularly of the back at a young age is common. Early onset degenerative disease of the joints and discs of the back is exacerbated by osteoporosis. Episodes of very severe pain are common. Back pain may be the main limiter of mobility. MRI scan information will usually be available if this is the case and referral for back surgery is common.

Some individuals may acquire blood borne viral infections as a result of repeated blood transfusions. These include HIV, hepatitis B and hepatitis C. Although blood is now screened for these conditions some people may have become infected while abroad or before routine screening was introduced in the UK. Hepatitis C (see relevant guidance) is the infection most likely to be seen in the UK in someone with Thalassaemia who has received regular blood transfusions. Treatment for this is usually given intensively over a year. Treatment makes Thalassaemia harder to manage, ribavirin causes dramatically increased haemolysis (destruction of red blood cells in the circulation). This increases transfusion requirements to 3-4 units of blood per fortnight. So much blood rapidly leads to iron overload so chelation treatment will need to be stepped up during ribavirin treatment. Additionally Interferon which is commonly used with ribavirin can cause sudden onset suicidal depression and careful monitoring of mood is mandatory.

Thalassaemia intermedia

This group is categorised by the fact that they do not require regular blood transfusions during early childhood to survive. There is much variation between individuals in the severity of their anaemia. Those with the most severe anaemia may only just manage without transfusion and be subject to persistent fatigue and shortness of breath on exertion. They may have poor growth, delayed puberty, abnormalities of the bones, gallstones and iron overload.

Those with milder anaemia may have few problems with their health. Some develop complications of long-term anaemia including enlarged spleen, gallstones, persistent ankle ulceration and chronic pulmonary hypertension.

Thalassaemia minor

People with the minor types of Thalassaemia/Thalassaemia carriers usually have no symptoms and live normal lives. They do not require treatment.

Amended May 2009