Thalassaemia 

What is thalassaemia?

Thalassaemia is the term given to a group of inherited blood conditions where the part of the blood known as haemoglobin (Hb) is abnormal. The abnormality means that the affected red blood cells are unable to function normally, which leads to anaemia (a red blood cell deficiency). The abnormality is caused by missing genes that instruct the body on how to make haemoglobin. Thalassaemia syndromes vary in severity and this is decided on by how many genes are missing.

Thalassaemia is a blood disorder that occurs worldwide. It's particularly common in Southeast Asia, and also affects people of Mediterranean, North African, Middle Eastern, Indian and Asian origin.

Red blood cells

Red blood cells are very important because they contain a substance called haemoglobin, which carries oxygen from the lungs to the rest of the body. Haemoglobin is produced in the bone marrow (a spongy material found inside larger bones) using the iron that the body gets from food.

In thalassaemia, haemoglobin production is abnormal, leading to anaemia and a reduced oxygen-carrying capacity. If your body doesn't receive enough oxygen, you can feel tired, breathless, drowsy and faint. If left untreated, the most serious types of thalassaemia can cause other complications, including organ damage, restricted growth, liver disease, heart failure and eventually death. Symptoms of anaemia include lethargy (a lack of energy), tiredness and breathlessness, particularly after exercise.

Who is affected by thalassaemia?

In England, beta thalassaemia major (BTM) is thought to affect around 1,000 people, with an estimated 300,000 people being carriers.

It most commonly affects people of Cypriot, Indian, Pakistani, Bangladeshi and Chinese origin. In the UK, eight out of 10 babies born with thalassaemia have parents of Indian, Pakistani or Bangladeshi ancestry.

Types of thalassaemia

Thalassaemia is caused by alterations (mutations) in the genes that make haemoglobin.

Haemoglobin is made up of matching chains of proteins, which are named after Greek letters of the alphabet. To work properly, haemoglobin needs a pair of alpha chain proteins and a pair of beta chain proteins.

A mutation that affects the alpha chain causes alpha thalassaemia, and a mutation that affects the beta chain causes beta thalassaemia. These are now known as Transfusion Dependent Thalassaemia (TDT) and Non Transfusion Dependent Thalassaemia (NTDT).

  • Alpha thalassaemia

    The alpha chains are produced by four genes, two on each chromosome 16, which are inherited as pairs. The severity of the condition will depend on how many of those genes have been altered. If one gene is mutated, there's little or no effect. If two genes are mutated (one on each chromosome), there may be symptoms of mild anaemia. This condition is known as the alpha thalassaemia trait, a person with thalassaemia trait is also known as a carrier.

    If two people with the alpha thalassaemia zero trait (when two genes on the same chromosome are altered) have a child, there's a one in four chance of the child inheriting the most severe form of alpha thalassaemia.

    If three genes are mutated, the result will be a condition called haemoglobin H (HbH) disease. Someone with this condition will have lifelong (chronic) anaemia and may require regular blood transfusions, but not always.

    If all four genes are mutated, the result will be the most severe form of alpha thalassaemia, known as alpha thalassaemia major. Infants with this condition are unable to produce normal haemoglobin and are unlikely to survive through pregnancy. There have been some cases of unborn babies being treated with blood transfusions while still in the womb, but this type of treatment has a low success rate and is not commonly undertaken.

  • Beta thalassaemia

    Unlike alpha genes, there are only two beta genes, one each on chromosome 11.

    Beta thalassaemia can range from moderate to severe. The most severe form of the condition is known as transfusion dependent thalassaemia (TDT)/ beta thalassaemia major (β thalassaemia major), where both beta genes are affected. People with TDT will require blood transfusions for life starting from a few weeks to months old.

    Beta thalassaemia intermedia (βThal int) is the milder form of the condition, which is also known as non-transfusion-dependent thalassaemia (NTDT). The symptoms of NTDT will vary from person to person. Some people will experience symptoms of mild anaemia, while others will need blood transfusions.

    These pages mainly focus on β Thal Major/ TDT, which is the most common and severe form of the condition in the UK.

What causes thalassaemia?

Thalassaemia is an inherited condition, which means it is passed on to you from your parents.

It's not known exactly what causes the genetic mutations associated with thalassaemia. However, it's likely they've survived because carriers of the condition (both alpha and beta thalassaemias) are protected against malaria.

This is why thalassaemia and other related genetic blood disorders, such as sickle cell anaemia, are more common in parts of the world where malaria is a problem, including certain Mediterranean countries such as Greece, Cyprus and Italy, the Middle East, Asia and sub-Saharan Africa.

Individuals with thalassaemia syndromes are encouraged to obtain genetic counseling before starting a family. More information can be found here:

http://www.nhs.uk/Conditions/pregnancy-and-baby/Pages/screening-sickle-cell-thalassaemia-pregnant.aspx

Living with TDT

Living with TDT can be challenging. You'll need to have regular check-ups to assess and reduce the risk of possible complications.

As well as the chronic anaemia complications of thalassaemia can include:

  • Iron overload – people with TDT need blood transfusions from an early age. This causes individuals to become overloaded with iron. The excess iron from the transfusions causes an accumulation of iron within the blood as well as in the organs. If left untreated, serious and potentially life threatening problems can occur. This can range from cirrhosis of the liver to diabetes. In order to treat this, individuals are given chelation therapy (see below) in order to remove the excess iron. Iron overloading also occurs in NTDT as they have increased gastrointestinal absorption of iron
  • An enlarged spleen – where the spleen has problems recycling red blood cells, making it grow larger
  • Hormone complications – including delayed puberty and restricted growth
  • Heart complications – such as an irregular or disturbed heartbeat (arrhythmia)
  • Liver complications – such as hepatitis (swelling of the liver) or an enlarged liver (fibrosis)

Bone complications – such as bone and joint pain and osteoporosis (where the bones become thin and brittle)

 Consultants

Dr Emma Drasar, Consultant Haematologist

Dr Emma Drasar

Emma Drasar is a consultant haematologist working between UCLH and the Whittington NHS trust. She trained at St Barts and the Royal London School of Medicine, University of London and qualified in 2001 and was awarded MRCP in 2006. She completed her haematology training at King's College Hospital being awarded FRCPath in 2015.

Dr Drasar was appointed Clinical Lecturer in Sickle Cell Disease at King’s from 2009 to 2013. During this time she was awarded a PhD based on research into markers of severity and predictors of organ dysfunction in sickle cell disease and in 2013 was awarded the Early Stage Investigator prize from the British Society of Haematology.

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Dr Perla Eleftheriou, Consultant Haematologist

Dr Perla Eleftheriou

Dr Perla Eleftheriou is clinical governance lead of the Red Cell Haematology department at UCH. Her area of special interest is Red Cell Disorders, which include haemoglobinopathies and rare anaemias, as well as polycythaemias and iron overload disorders. Dr Eleftheriou teaches haematology at the London School of Hygiene and Tropical Medicine and is a visiting lecturer of haematology at the Nicosia Medical School in Cyprus. Dr Eleftheriou also serves as clinical/scientific adviser to Thalassaemia International Federation and is a member of the UK Thalassaemia Society.

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Professor John Porter, Consultant Haematologist

Prof John Porter

Professor John Porter is a consultant haematologist at UCLH, professor of Haematology at UCL and head of the joint Red Cell Unit for UCLH and Whittington Hospitals. His main clinical and research fields have been the treatments of thalassaemia and sickle cell disorders, with particular reference to iron overload in these conditions. Professor Porter has published more than 150 peer-reviewed articles, and has made numerous contributions to books, as well as clinical guidelines and other medical articles.

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Dr Farrukh Shah

Dr Farrukh Shah

Dr Farrukh Shah was awarded her MD thesis for research in iron chelation at University College London. She has already built an international reputation in the management of iron problems and of thalassaemia

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Dr Sara Trompeter, Consultant Haematologist

Dr Sara Trompeter

Dr Sara Trompeter is a consultant haematologist and paediatric haematologist. She specialises in red cell and iron disorders in children and adults, including sickle cell, thalassaemia, enzymopathies, membranopathies and haemochromatosis. Sara also works with the transplant team to develop the haemoglobinopathy stem cell transplant programme for adolescents.

Her main research interest is transfusion in sickle cell disease and thalassaemia, and she also has an academic role with NHS Blood and Transplant to develop and evidence base for transfusion in haemoglobinopathies.

“The most rewarding part of my role at UCLH is that I am constantly interacting with brilliant collaborative colleagues who can inspire and motivate you. The atmosphere at UCLH generated by staff, encourages innovation and improvement in treatments for patients. The junior doctors are also of an extremely high standard.”

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 Clinical Nurse Specialists (CNS)

Bernadette Hylton, Haemoglobinopathies Clinical Nurse Specialist

Bernadette Hylton

Bernadette specialises in sickle cell disease, thalassaemia and conditions associated with red blood cells. She currently doing research in health related quality of life in sickle cell disease as part of her Masters degree.

“The most enjoyable part of my job is getting to know my patients and having a positive impact on their life”.