Thalassaemia (transfusion-dependent and non-transfusion-dependent) : University College London Hospitals NHS Foundation Trust

What is thalassaemia?

Thalassaemia is a disorder of the body’s red blood cells that is genetically inherited and lifelong. It is caused by an abnormality in the genes that control haemoglobin, the part of red blood cells that carries oxygen around the body. This results in the reduced amount of normal haemoglobin. Most of the normal haemoglobin produced by the foetus in the womb is Haemoglobin F (HbF – F is for foetal). Shortly before birth the production switches to Haemoglobin A (HbA – A is for adult).

By 18 months of age children with normal haemoglobin production make very little HbF. Most of their haemoglobin is the HbA type. In most cases of thalassaemia, babies are born without any problems as they make the HbF normally. As they get older, the production of HbF stops and they cannot make HbA. The way this happens is different in different people. Often, it depends on what exactly the genetic problem is.

When the haemoglobin gets low, the body tries even harder to produce the red blood cells. But as they don’t contain much haemoglobin, the person becomes anaemic. This effort can make some of the organs too big, for example the liver and spleen. It can also change the shape of the face.

Currently people start treatment before any significant side effects are present. The timing of this can vary from infancy (previously known as thalassaemia major) to later in life (previously known as thalassaemia intermedia treated as major). These disorders are now referred to as transfusion-dependent thalassaemia (TDT).

Some people may not need transfusions until much later in life, or perhaps never. These people have non-transfusion-dependent thalassaemia (NTDT).

Problems in thalassaemia can come from:

the condition itself
the extra iron from blood transfusions
the extra iron that may be absorbed from food
the medications taken to lower iron levels in the body.

Following your treatment plan carefully is important for better health and a longer life.

Problems related to anaemia

Anaemia can make people feel very tired and may slow down their growth. In babies, severe anaemia can cause poor feeding. Older children may lose their appetite. Their tummy may also swell because of an enlarged liver and spleen. The bone marrow can expand, leading to thinner bones and swelling in the facial bones, which is typical of thalassemia. These signs usually mean that the child will need to begin a transfusion programme.

The transfusion programme will involve having regular blood transfusions. They usually take place every three to four weeks. This helps to keep the haemoglobin levels high enough to reduce or prevent symptoms. If the haemoglobin stays at a good level (usually above 95g/L), the child will grow well and look like any other healthy child.

People with NTDT may eventually need regular blood transfusions, like those who started them in early childhood. Sometimes they may need an occasional transfusion or a course of transfusions. This is usually due to a temporary issue, such as infection or pregnancy.

Problems related to transfusion

Blood transfusions can be lifesaving for people with thalassaemia but they come at a cost. Each time you have a transfusion, you also receive iron which is an essential part of haemoglobin. The body can't naturally get rid of this extra iron, so we need to use medications to help remove it. These medications are called iron chelators and the treatment is called iron chelation therapy.

These medications were not available in the 1950s, so patients often developed serious complications from iron overload and most died. When extra iron is not removed, it builds up in different parts of the body. It can build up in the liver but also in the heart, pancreas and hormone-producing glands. This results in serious problems, such as:

diabetes
stunted growth and delayed puberty
infertility
low thyroid function
liver disease
heart disease.

Heart disease is the most serious and is usually the cause of death in people who don’t have access to chelation treatment.

Even people with NTDT are at risk of iron overload and the complications associated with it. This can be because of occasional transfusions they may need, or due to an increased iron absorption from food. For this reason, we monitor all patients carefully for signs of iron overload.

Infection

People with excess iron in their body may become very sick very quickly if they have an infection. They are also more likely to get rare types of infection. If the extra iron is in their heart, it can make it especially hard for them to cope with an infection.

Blood transfusions

If you have TDT, you will need regular blood transfusions to keep your Hb above 95g/L. Your doctor may decide to raise this level if needed.

Children often have their blood transfusions on weekends. Adults can have theirs overnight or on weekends, if arranged in advance. Most people prefer to come to Supportive Care (adults) or Day Care (children) for their transfusions.

Chelation therapy for iron overload

When your ferritin levels start to reach 1000, we will offer you chelation therapy to help manage iron build-up. Ferritin is a protein that stores iron in the body.

Your doctor will give you more information about the different types of chelation treatment. They will also recommend the one that's best for you. These treatments may include:

deferasirox: a tablet you take once a day
desferrioxamine (also known as Desferal®): an injection given under the skin over several hours, a few days a week
deferiprone (also known as Ferriprox®): a tablet you take three times a day
or a combination of these.

Hydroxyurea

Hydroxyurea can help to increase your HbF levels. It may be suitable if your condition is less severe.

Stem cell transplant

A stem cell transplant is currently the only treatment that can cure the disease. These transplants are often done in childhood if the child has a sibling with matching bone marrow. Transplants where children received bone marrow from a parent are rare, so we don't have much information about the risks involved.

Gene therapy and gene editing

These treatments are similar to transplants and are currently being tested in clinical trials.

Gene therapy involves adding a normal gene to help your body to produce normal HbA.
Gene editing involves changing a gene to increase haemoglobin production.

Although these treatments are licensed, they are not currently available through the NHS. We hope they will be more widely available as a cure in the future.

Other treatment options

Other treatments may depend on any complications you experience from thalassaemia. Talk to your doctor or nurse if you have any concerns about your health or treatment. They will assess your situation and monitor your treatment closely.

For non-urgent medical problems or medical problems unrelated to your thalassaemia, for example a rash or a twisted ankle:

contact your GP or go to your local Emergency Department (A&E). If necessary, they can contact us to discuss your problem.

For non-urgent problems related to your thalassaemia:

ask for your outpatient appointment to be brought forward. You may also be able to have a review in Haematology Day Care.

If you are unwell, you should call the haematology advice line (office hours) on 020 3447 7359. It is manned by administrative staff who will contact your clinical team. Out of hours, call the adult haematology advice line on 07852 220 900 or paediatric helpline on 07950 869745. They are manned by a senior haematology ward nurse who will contact the on-call team.

Even if you are going to an Emergency Department, it is always best to call ahead. We can then try to streamline your assessment as much as possible. We can also make sure that the team treating you have a good understanding of your symptoms.

If you go to an Emergency Department in another hospital, it may take a few days to transfer you to UCLH. We are always happy to support other teams but we would not be able to coordinate your care at another hospital. To avoid any potential delays with transfer, you should try to come to the Emergency Department at UCLH if possible.

Note: If you have an infectious illness, such as cough, cold, diarrhoea, vomiting or chicken pox, do not come to clinic or Haematology Day Care. You should go to the Emergency Department and we will see you there. These seemingly minor illnesses can be very serious for some people with blood conditions and very poor immune systems. For example, those recovering from chemotherapy or stem cell transplants.

Please go to the Emergency Department (A&E). Try to ring your child’s CNS before you come in so that they can contact the Emergency Department’s team.

If you go to an Emergency Department in another hospital, it may take a few days to transfer your child to UCLH. We are always happy to support teams in other hospitals but we would not be able to coordinate your child’s care at another hospital. To avoid any potential delays with transfer, you should try to come to the Emergency Department at UCLH if possible.

The following symptoms require immediate medical attention:

Fever: 38°C or above
Chills
Diarrhoea or vomiting
Feeling very unwell
Palpitations
New weakness.

Thalassaemia is an inherited condition so it can’t be prevented.

Each carrier (trait) parent may pass on an affected gene to their child. If both parents are carriers of the beta thalassaemia gene, the chance that their child will have thalassaemia is one in four. If one person has the disease and the other is a carrier, the risk is greater – one in two.

A thalassaemia gene combined with a sickle gene may result in sickle cell disorder.

We know that the genetics of thalassaemia are complicated. If you have any questions or worries, you can talk to our haemoglobinopathy geneticist.

Contact us as soon as you or your partner become pregnant. We will arrange any necessary tests and counselling if needed. We also ask our patients to tell us as soon as they have met their partner so that we can offer testing at an early stage.

If you need blood transfusions, schedule them in a way that the levels of your Hb are kept higher than 95 g/dL.
Take your chelation therapy exactly as advised. This may be every day.
Make sure infections are treated quickly.
Maintain a good balance of nutrition and activity.
Make sure your vaccinations are up to date.
Avoid smoking.
Take penicillin twice a day for life if you don’t have a spleen.
Attend your clinic appointments so that we can review your health and monitor you for any complications.

Attending your clinic appointments is a requirement stated in the National Standards produced by the Sickle Cell Society and NHS England. These appointments are every six to 12 months in healthy people. They may be more frequent if you have health problems.

If you don’t have an appointment, please ask your GP to refer you.

If your appointment is inconvenient, please change it. We will do our best to schedule an appointment that is convenient for you.

The NHR is a database of people with red cell disorders (mainly sickle cell and thalassaemia) living in the UK. The overall aim of the registry is to improve patient care. It helps the NHS England to understand the specific needs of these patients and improve access to treatment.

The registry is currently being updated. It will have a patient portal where you can access your information. It will also include a research component. Your team will discuss this with you at a clinic appointment.

Mortimer Market Centre offers a wide range of sexual health services. This includes testing for sexually-transmitted infections (STIs) and HIV.

You need to book an appointment to attend the clinic, except for walk-in HIV testing clinics. You can phone the clinic for advice if you have an urgent problem or to find out the opening times.

Mortimer Market Centre

Address: Mortimer Market Centre, off Tottenham Court Road, London, WC1E 6JB

Telephone: 020 3317 5252

The Reproductive Medicine Unit offers a wide range of tests and treatments for couples who experience fertility or hormonal problems, or recurrent miscarriages. You can see a reproductive medicine consultant who will arrange the necessary tests and refer you for further care if needed.

You can talk to your GP, local family planning clinic or community sickle cell and thalassaemia nurse about contraception. You should tell them about your thalassaemia and any other medical problems you may have because of thalassaemia.

If there are any changes to your medication, please let the red cell team know.

If you would like to be referred to the UCLH stop smoking service, please speak to your nurse specialist. You can also find helpful information on the NHS Better Health website.

Haematology admin team:

uclh.redcelladminteam@nhs.net

Haematology clinical nurse specialists (CNSs):

uclh.redcell.cnsteam@nhs.net

Haematology advice line (office hours, adults and children):

020 3447 7359

Adult haematology advice line (out of hours):

07852 220 900

Paediatric helpline (out of hours):