Sickle Cell Disease and Sickle Cell Anaemia

What are sickle cell anaemia and sickle cell disease?

Sickle cell anaemia (SCA) is a serious condition which is genetic (inherited). It affects the red blood cells in the blood. With SCA, the red blood cells have a tendency to go out of shape and become sickle-shaped (like a crescent moon) - instead of their normal disc shape. This can causes various problems, such as episodes of pain, infections and various complications. In between the episodes of illness, people with SCA feel well.

Who gets sickle cell disease?

In the UK, approximately ten thousand people have sickle cell disease. It is more common in people whose origins are African, African-Caribbean, Asian or Mediterranean. It is rare in people of North European origin. On average, 1 in 2,400 babies born in England have sickle cell disease, but rates are much higher in some urban areas - about 1 in 300.

What causes sickle cell disease?

The cause is inherited. It is a change in the genes which tells the body how to make an important chemical called 'haemoglobin'. To get SCD, you need to have two altered haemoglobin genes, one from each parent. If you only have one of these genes, you will have 'sickle cell trait', which is very much milder. See separate leaflet called 'Sickle Cell Trait and Sickle Cell Screening Tests' for more detail.

• Haemoglobin SC
• Haemoglobin S/beta thalassaemia
• Haemoglobin S/Lepore
• Haemoglobin SO Arab

How do the sickle cell genes cause sickle cell disease?

Sickle cell genes affect the production of an important chemical called haemoglobin. Haemoglobin is located in red blood cells, which are part of the blood. Haemoglobin carries oxygen and gives blood its red colour.

The sickle cell genes make the body produce abnormal haemoglobin called HbS. (Normal haemoglobin is called HbA.) HbS behaves differently from normal haemoglobin. Under certain conditions, HbS makes the red blood cells change shape - instead of the normal doughnut shape, they become sickle-shaped, like a crescent moon. This is called 'sickling'. Conditions which trigger sickling are: cold, infection, dehydration (lack of body water), low oxygen, and acid (acid is produced in hard physical exercise).

What happens to the sickle cells?

The sickle cells are harder and less flexible than normal red blood cells. So, they can get stuck in small blood vessels and block them. This can happen quite suddenly, and causes various symptoms which are known as a 'sickle cell crisis' (explained below). Repeated blockages can also lead to complications later in life.

Also, the sickle cells are destroyed more easily than normal red blood cells. This means that people with SCD tend to be short of red blood cells and have a moderate and persistent anaemia. This moderate anaemia is not usually a problem because the HbS (the different haemoglobin) carries oxygen well, and the body can compensate. However, you may get bouts of severe anaemia for various reasons: if too much blood goes to the spleen, if too many red blood cells break down at the same time, or due to certain infections which stop blood cells being made. A severe anaemia can make you very ill.

How is sickle cell disease diagnosed?

The diagnosis is made by a blood test. The blood sample is analysed to see what type of haemoglobin is present in the blood (using a test called 'haemoglobin electrophoresis' or other methods).

In England, there is a screening programme to test pregnant women and newborn babies for SCD and other haemoglobin disorders. See separate leaflet called 'Sickle Cell Trait and Sickle Cell Screening Tests' for more detail.

What are the symptoms of sickle cell disease?

Symptoms of SCD come and go. Usually there are episodes (bouts) of symptoms, but in between episodes you feel well. The reason that symptoms come and go is that the red blood cells can behave normally for much of the time - but if something makes too many of them sickle, the sickle cells cause symptoms. If there are severe and sudden symptoms due to sickling, this is called a 'sickle cell crisis'.

There is a lot of individual variation in symptoms - how many and how often you get them. Some people with SCD have frequent symptoms, while others have very few and their SCD is hardly noticeable. For most people, symptoms are somewhere in between these two extremes.

Symptoms usually begin at around age 3-6 months. (Before that age, the baby has a different haemoglobin, called fetal haemoglobin, which is not affected by the sickle cell gene.)

There are various symptoms that can occur if you have SCD:

Episodes of pain

These are also called a 'pain crisis' or a 'vaso-occlusive crisis'. They occur when sickle cells block small blood vessels in bones, which causes pain. The pain can vary from mild to severe, and may come on suddenly. A common symptom in babies and young children is when small bones in the fingers and toes become swollen and painful - this is known as 'dactylitis'.

Episodes of abdominal (tummy) pain can occur if sickle cells block blood vessels in the abdomen.

Acute chest syndrome

This occurs when there are blocked blood vessels in the lungs, and/or a lung infection. The symptoms are chest pain, fever and shortness of breath. Babies and young children may have more vague symptoms and look generally unwell, be lethargic, restless or have fast breathing. Acute chest syndrome can be very serious, and should be treated urgently in hospital.

Infections

People with SCD are more susceptible to severe infections, particularly from certain types of bacteria, which can cause pneumonia, meningitis, septicaemia or bone infections. (These are the pneumococcal and meningococcal bacteria, and salmonella bacteria which can infect bones.) Symptoms of infection include fever, feeling generally ill, and pain in the affected part of the body.

Children with SCD have a high risk of getting severe or life-threatening infections, and young children are particularly at risk. It is important to see a doctor quickly if you suspect an infection or feel unwell.

Anaemia episodes

Anaemia is a lack of haemoglobin (the red colour) in the blood. As mentioned above, people with SCD will usually have a moderate anaemia, which does not usually cause problems. However, at times, people with SCD can get a severe anaemia, which can be serious. It may come on very suddenly or more gradually. Urgent treatment may be needed.

Symptoms of severe anaemia are:

• Feeling tired, faint, short of breath, dizzyness, nausea or having fast breathing - worse with physical activity.
• Babies and small children may be lethargic, not feeding much or generally unwell.
• A pale skin colour (sometimes easiest to see in the lips, tongue, fingernails or eyelids).
• With children, the spleen sometimes enlarges quickly and causes sudden severe anaemia. The enlarged spleen is in the abdomen (tummy) and can be felt. Parents may be shown how to feel their child's spleen. If the spleen enlarges quickly, it is a sign that urgent treatment is needed.

Is there a cure for sickle cell disease?

A possible cure in some cases is bone marrow transplant.This treatment takes normal blood-making cells from a donor, and gives them to the person with SCD. If the transplant is successful, these cells last for life and make normal haemoglobin - a lifelong cure. However, a bone marrow transplant is not suitable for everyone. You need a suitable donor, and there are some serious risks involved. UK guidelines recommend that all children with SCD (and their families) have the opportunity to discuss bone marrow transplant with a specialist.

What is the treatment for sickle cell disease?

In many cases, SCD cannot be cured, so lifelong treatment and monitoring is needed. There are a number of different treatments which help to prevent sickling episodes, or prevent related problems such as infection.

Principles of treatment

• You should be treated by a specialist doctor or team, who are experienced in treating patients with SCD. If the specialist is a long way from your home, then some of your treatment may be with a more local hospital or doctor - but the local doctors should get advice from your specialist.
• Because symptoms of SCD can start suddenly, you should be able to see a doctor and get hospital treatment urgently, as and when needed.
• You can be shown how to recognise symptoms (in yourself or your child), so that treatment can be started quickly.
• Treatment should be tailored to your individual needs, and you can be involved in decisions.
• It is important to take preventative treatments against infection, and to attend your checkups.

Staying healthy

• A daily antibiotic should be taken (penicillin, or erythromycin if you are allergic to penicillin). This has been proved to protect against serious infections in young children. Side-effects from antibiotics are very unlikely in this situation.
• Immunisations: all the usual childhood vaccinations are advised, PLUS you should have vaccinations against pneumococcus, meningitis and hepatitis B, PLUS a flu (influenza) vaccination once a year.
• Vitamin supplements: extra folic acid, vitamin D and zinc are recommended.
• Travel: if you go to a country where there is malaria, then be extra careful to take malaria prevention medication and to prevent mosquito bites (people with SCD can get very ill from malaria).
• Avoid smoking (which is bad for blood vessels) and excess alcohol.

Avoid factors which can trigger sickling

Factors which can trigger sickling include: cold, lack of oxygen, dehydration, hard exercise, fever and infection. So it can help to:

• Drink plenty of fluid.
• Avoid getting cold; wrap up well. Avoid over-exertion.
• Treat infections and fevers quickly. You will usually be given detailed advice about how to check for signs of fever or infection in yourself or your child, and how to get treatment quickly.
• See a doctor quickly if you feel unwell. Tell doctors and nurses that you have SCD.
• It is probably best to avoid wearing clothing or appliances which are very tight or constricting. A recent report suggested that pressure garments (sometimes used for medical reasons) may trigger sickling.

Treatment of sickling episodes

If blood cells do sickle, then early treatment can help them return to normal, or may at least stop the problem getting worse. This involves:

• Painkillers. Depending on the amount of pain, you can take various types of pain medication. Mild painkillers are paracetamol or ibuprofen. Moderate ones are codeine or dihydrocodeine. A strong painkiller such as morphine may be needed for severe pain - this is given in hospital.
• Good hydration. This can mean drinking extra fluid, or sometimes a 'drip' is needed if you are more unwell.
• Antibiotics. These are used if you have an infection, or when infection is suspected. (You will normally be taking a regular preventative antibiotic already, as explained above. But if an active infection is suspected, you will need a different antibiotic in a higher dose.)

Depending on how unwell you are, treatment may be at home or in hospital.

Blood transfusions

Blood transfusion is a useful treatment for some situations, such as acute chest syndrome or severe anaemia. It can also be used to help prevent or treat certain complications (see below). The transfusion helps because it adds normal red blood cells to the blood. This corrects anaemia and reduces the effects of sickling. There are potential side-effects from blood transfusions. Therefore, transfusions are given for a specific need, rather than routinely.

Treatment of acute chest syndrome

For acute chest syndrome, some of the treatment is the same as for sickling episodes (above) - painkillers, hydration and antibiotics. Also, you may need a blood transfusion and oxygen. A type of chest physiotherapy called 'incentive spirometry' also helps.

Hydroxyurea

Hydroxyurea (also called hydroxycarbamide), taken regularly, may help to reduce the amount of symptoms such as pain episodes and acute chest syndrome. Hydroxyurea can have serious side-effects, and needs monitoring with blood tests. It may be an option, but you and your doctor need to think about the pros and cons of taking it.

Women's health

Contraception
In general, most types of contraception can be used by women with SCD (depending on your individual situation and preferences). However, you may like to know that SCD symptoms can be helped by using one particular type of contraceptive. This is the 'depot' injection called Depo-Provera. Research found that this contraceptive improved the blood and reduced pain episodes for women with SCD.

Planning a baby and pregnancy
Having SCD increases the risk of certain problems in pregnancy, such as high blood pressure or premature birth. Also, your SCD symptoms might increase while you are pregnant. Be aware that some medications such as hydroxyurea should be avoided if you are trying to conceive or become pregnant. So, when planning a pregnancy or when pregnant, see your doctor early on. You will normally have extra monitoring from a specialist during your pregnancy.

You may wish to have tests for your partner and unborn baby, to find out whether your baby could inherit sickle-cell disease. This is explained in more detail in the separate leaflet called 'Sickle Cell Trait and Sickle Cell Screening Tests'.

Anaesthetics and operations

An operation or anaesthetic is one of the things that can trigger sickling. Therefore, always tell your anaesthetist, surgeon and other healthcare staff that you have SCD, so that precautions can be taken to reduce the risk of sickling. For example, sometimes a blood transfusion before the operation or anaesthetic may be advised.

What are the possible complications of sickle cell disease, and how are they prevented or treated?

Possible complications in children

Growth, development and nutrition
As with any long-term illness, a child with SCD may grow more slowly than usual, or be undernourished if the illness affects their appetite. Your child's growth, development and nutrition should be checked regularly, and nutritional supplements may be given if needed.

Some children with SCD take longer than usual to gain control of their bladder at night, so may wet the bed. (The medical name for this is nocturnal enuresis.) We don't know why this sometimes happens with SCD. Various treatments can help.

For teenagers, puberty may start about 2-3 years later than average.

The growth of bones can also be affected. For example, there may be changes in the hip or shoulder joints due to blocked blood vessels in that part of the bone. If a joint is severely affected, surgery may be needed.

Stroke or brain injury
This is a serious complication and affects about 1 in 10 children or teenagers with SCD. If sickle cells block blood vessels in the brain, this may cause a stroke. There may be symptoms of stroke such as weakness of the face or limb, or speech difficulty. For some children, there may be no obvious symptoms. However, many tiny strokes may cause a subtle brain injury and make learning more difficult.

Strokes are treated with blood transfusion, which improves blood flow to the brain. Also, recent research found that blood transfusions help to prevent strokes. An ultrasound test called a 'transcranial Doppler' can be used to look at the blood flow to the brain. This helps doctors to decide whether your child needs blood transfusions for prevention. Children aged over three years should be offered these scans.

Spleen problems
The spleen is an organ located in the abdomen (tummy), in the top left-hand side. Its function is to help the immune system. Sickle cells can block blood vessels in the spleen. This can make the spleen swell up suddenly with blood - in effect, it is like losing blood into the spleen. This is one cause of sudden and severe anaemia, when your child becomes suddenly ill. The medical term is 'splenic sequestration'. It needs urgent treatment with a blood transfusion. If this problem happens often, then one option is surgery to remove the spleen. But, by adulthood the problem normally resolves because the spleen becomes fibrosed (hard) and cannot swell.

Parvovirus infection
Parvovirus is a common infection in childhood. Normally it causes a mild illness with fever, flushed cheeks and a rash. With SCD, the virus can upset the bone marrow, which then stops making blood for a while. This causes a severe anaemia and needs treating with blood transfusions until the bone marrow recovers.

Complications of blood transfusions
Transfusions can cause blood reactions. These are less likely if the blood is carefully matched to your blood type. Infections such as hepatitis B and C can be transmitted by transfusion. This is less likely in the UK and countries where donor blood is tested for infections. Hepatitis B vaccination is also recommended.

Repeated blood transfusions can overload the body tissues with iron. You may need tests to measure the iron level in the body. If iron levels get high, you may need treatment called chelation, which helps the body get rid of excess iron.

Possible complications in older teenagers and adults

Damage to various organs can develop gradually during teenage and adult years, due to repeated, small blockages of tiny blood vessels. The amount of complications varies from person to person.

Lungs, heart and kidneys
Any of these organs may suffer some damage. Therefore, you will normally be offered regular checks on your heart, lungs and kidney function. Various treatments can help.

Eyes
Regular eye checks are important. SCD may cause changes to blood vessels in the back of the eye (retina); this is called 'retinopathy'. For retinopathy, laser treatment is given to prevent further damage.

Also, sickle cells may cause sudden blockage of a blood vessel in the eye. If this happens, you will have a sudden reduction in your vision. This needs immediate treatment. So, always see a doctor quickly if your vision reduces suddenly in any way.

Unwanted erections
Some teenage boys and men with SCD may get unwanted erections of the penis, which may be painful. The medical name for this is 'priapism'. This can be quite brief, but if an erection does not subside then urgent treatment is needed. There are various treatments to relieve or prevent unwanted erections.

Gallstones
Stones in the gall bladder are more common in people with SCD, and can cause bouts of pain in the upper right side of the abdomen (tummy). They may need treatment.

Leg ulcers
Leg ulcers can occur with SCD, but are not common. Treatment is with dressings, and zinc supplements may help.

Complications of blood transfusions
These are explained above for children, and also apply to adults.

What is the outlook with sickle cell disease?

SCD is a serious condition which may shorten life. Without treatment, people with SCD may die in childhood from problems such as infection. Good treatment makes a great difference. Average life expectancy in 2003 for people with SCD in the UK was around 50 years. Improvements in treatment mean that life expectancy may increase in future.

Even with modern treatment, SCD can still cause serious or life-threatening problems. Dangerous problems are severe infection, acute chest syndrome and sudden severe anaemia. Awareness of symptoms and early treatment is important.

There is a lot of individual variation in the severity and outlook for SCD. Some people get very few problems from their SCD; others have more symptoms or more complications.

Further information and help

Sickle Cell Society

54 Station Road, London, NW10 4UA
Tel: 020 8961 7795
Promotes awareness and information about sickle cell disease.
Web: www.sicklecellsociety.org

The Sickle Cell Information Center

A USA website with information about sickle cell disease for patients, families and medical staff.
Web: www.scinfo.org/

Brent Sickle and Thalassaemia Centre

122 High Street, Harlesden
London NW10 4SP
Web: www.sickle-thalassaemia.org

List of specialist centres for thalassaemia and sickle cell disease

Web: www.sickle-thalassaemia.org/Centres.htm