Treatment of beta-Thalassaemia

Treatment of affected children and adults is usually undertaken in a specialist Thalassaemia centre with expertise in all aspects of these uncommon blood disorders

The cornerstone of the treatment of Thalassaemia major is regular blood transfusion, given on a 3 - 4 weekly basis. The transfusion takes 4 – 6 hours and is usually given in hospital. The aim of transfusion to maintain a haemoglobin level of 9.5 – 11 g/dl. Normal haemoglobin level is 11 - 13 g/dl. Transfusion corrects the anaemia, enables normal activity, encourages normal growth, prevents enlargement of the spleen and inhibits the excess bone marrow activity that causes bone deformity and thinning.

People with Thalassaemia intermedia may need transfusion on occasions to correct severe anaemia, but it is important to avoid unnecessary transfusion in order to minimise iron overload. Women may need transfusion during pregnancy. The role of transfusion is to improve the quality of life by relief of symptoms; it is not necessary to sustain life, unless serious complications develop. Examples of serious complications include:

• Extramedullary haematopoiesis-blood cells are manufactured in the bone marrow of some bones e.g. the long bones and pelvis. In chronic anaemia, stem cells in other bones may also start producing blood cells. One of the effects of this is expansion of the involved bone. When bones of the spine are involved this may lead to compression of the spinal cord. Early symptoms of this are likely to include severe back pain, which after several months may progress to neurological problems such as weakness or paralysis of the legs and faecal and urinary incontinence. Urgent treatment is required and in the majority of cases the neurological signs resolve. Mobility may be severely affected for 6-12 months during the treatment and recovery phase.
• Pulmonary hypertension – symptoms include progressive breathlessness and eventually right-sided heart failure, this may not completely resolve with treatment. Mobility is likely to be affected.

Treatment is required to avoid or ameliorate the complications of iron overload in Thalassaemia major and in some people with Thalassaemia intermedia. Iron overload is treated with a chelating agent – a substance that is able to bind with excess iron in the body and enable it to be excreted. Iron chelation therapy is time consuming and has unpleasant side effects.

Chelation therapy may be given as an infusion using Desferrioxamine subcutaneously or intravenously. Depending on the severity of iron overload the infusion can be given over 8 hours 5-7 days a week or 24 hours a day every day.

A common regimen is 12 hourly infusions 3-5 times a week. Constant treatment is likely to be given in hospital as part of the treatment of life threatening complications of iron overload such as heart failure. Complications of iron overload such as heart failure can occur suddenly, this is because iron can build up in the tissues and cause toxic effects very rapidly.

An oral chelation agent is available – deferiprone – this is given three times a day 7 days a week. The dose may consist of up to 16 large tablets to be taken on each occasion. This treatment has severe side effects including:

• Neutropenia – reduced white blood cell count - this can lead to life threatening septicaemia – weekly blood test monitoring is required during treatment.
• Arthropathy and joint destruction

Another oral chelation agent called Deferasirox is also available and this has different but equally severe side effects including:

• Kidney toxicity and reduced renal function in 30%
• Liver toxicity in 2%
• Severe diarrhoea

Chelation treatment of one sort or another needs to be commenced usually within one to two years of starting regular transfusions. The amount of iron in the body is monitored regularly by special investigations. It is difficult to comply with these treatments because of side effects, the time-consuming nature of treatment and no immediate and obvious benefit from adhering to them carefully.

Later problems with iron overload increase mortality, if the young person defaults from chelation therapy.

Children and adults should be fully vaccinated. Those who have had their spleen removed should take penicillin on a daily basis to reduce the risks of infection. Those with Thalassaemia intermedia should take regular folate to replace that destroyed by haemolysis.

Surgical removal of the grossly enlarged spleen may be advised to improve the anaemia and relieve abdominal discomfort

Bone marrow transplantation may be curative if a suitable match can be found. There are significant risks and complications associated with this procedure.

Cord blood transfusion is another potentially curative treatment for Thalassaemia major. Blood is taken from the umbilical cord at birth of a sibling who does not have Thalassaemia and transfused subsequently into the older affected sibling. The umbilical blood contains stem cells that are capable of producing healthy red blood cells in the recipient.

Prevention of Thalassaemia

In parts of the world where Thalassaemia is common, screening programmes have been introduced to identify individuals carrying the abnormal genes. Screening is offered to family members of known cases, couples planning a pregnancy and in the antenatal period. Genetic counselling is offered to those who have the Thalassaemia genes. Techniques are also available to determine whether a foetus has one of the severe types of Thalassaemia. In Sardinia, Greece and Cyprus there has been a significant decrease in the number of new cases of Thalassaemia occurring in the community following screening programme introduction.

Screening for Thalassaemia is available in the UK.

Amended May 2009