A genetic mutation is a permanent alteration in the normal pattern of DNA that makes up genes. Genes consist of coiled strands of DNA, and each cell contains the same genetic material.

Haemoglobin

Haemoglobin is a substance that is found in red blood cells. It acts as a sort of transport mechanism for your blood.

As blood passes through your lungs, the haemoglobin will pull in oxygen molecules while at the same time releasing carbon dioxide molecules. After moving away from your lungs, the haemoglobin will deliver oxygen molecules to the body’s tissue and will pull in any excess carbon dioxide molecules to take back to your lungs.

The exchange process, where haemoglobin pulls in oxygen and releases carbon dioxide, is known as oxygenation. The process where haemoglobin pulls in carbon dioxide and releases oxygen is known as deoxygenation.

During deoxygenation, healthy haemoglobin molecules should smoothly rearrange themselves into a different shape.

In cases of sickle cell anaemia, the smooth rearrangement does not occur due to the mutated gene. Instead, the haemoglobin inside the blood cells clumps together into solid structures. The clumping distorts the normal shape of the red blood cells, causing the cells to take on a rigid, sickle shape that is characteristic of sickle cell anaemia.

The genetics of sickle cell anaemia

Haemoglobin is created by a pair of genes, one of which is inherited from your mother, the other from your father.

To develop sickle cell anaemia, you must receive two copies of the mutated gene (one from your father and one from your mother).

If you only receive one copy, you will not develop sickle cell anaemia, but you will be a carrier of the sickle cell gene. This is often referred to as having the sickle cell trait. It is estimated that 1 in 10 people of African or Caribbean descent has the sickle cell trait. 

If you have the sickle cell trait, you will not usually notice any obvious symptoms, unless you are in an environment where the oxygen levels are lower, such as on top of a mountain or in a balloon at high altitude.

If both you and your partner have the sickle cell trait, there is a risk that any children that you conceive will inherit a pair of mutated genes and develop sickle cell anaemia. The chances of sickle cell anaemia being passed on are outlined below:

• There is a one in four chance that your baby will receive a pair of normal haemoglobin genes.
• There is a one in two chance that your baby will receive one normal gene and one mutated gene. In this case, they will not have sickle cell anaemia, but they will have the sickle cell trait.
• There is a one in four chance that your baby will receive a pair of mutated genes. This means that they will have sickle cell anaemia.

If one parent has the sickle cell trait and the other parent has normal haemoglobin, their baby will not get sickle cell anaemia. However, there is a one in two chance that the baby will receive the sickle cell trait.

Sickle cell anaemia can be diagnosed with a blood test. The blood can be checked for the presence of defective haemoglobin. A small level of defective haemoglobin would suggest that you have the sickle cell trait, but not sickle cell anaemia. A high level would suggest that you have sickle cell anaemia.

Antenatal screening

The purpose of antenatal screening (screening that is carried out during pregnancy) is to check for inherited disorders, such as sickle cell anaemia, and to provide parents with the information that they need to make informed decisions.

Antenatal screening for the sickle cell trait is available in areas where the condition is most common. These are typically cities and towns that have large black communities. In areas where sickle cell anaemia is uncommon, a questionnaire that focuses on family origin is used as an initial screening device to assess the risk of sickle cell disorders.

Pregnant women are routinely screened for the sickle cell trait. If they test positive for the trait, their partner will also be offered the test. If both parents have the sickle cell trait, there is a one in four chance that their baby will have sickle cell anaemia.

Further testing is available (if you want it) to confirm whether your baby will definitely be born with sickle cell anaemia. One method is to take a sample of cells from the placenta (the organ that is attached to the womb lining during pregnancy). This test is commonly known as chorionic villus sampling (CVS).

Counselling

Being told that your baby will be born with sickle cell anaemia can be a traumatic and upsetting experience. Therefore, you will be offered counselling to give both you and your partner the opportunity to express your feelings, and to ask questions about how the diagnosis may affect you.

The counsellor will be able to make you aware of the different options that are available to you, allowing you to make a more informed decision about how to proceed with the pregnancy.

Pre-implantation Genetic Diagnosis (PIGD)

Pre-implantation Genetic Diagnosis (PIGD) is an option for couples who do not want to give birth to a child with sickle cell anaemia but are unwilling, for whatever reason, to terminate a pregnancy.

PIGD is similar to in vitro fertilisation (IVF). IVF is a method of helping infertile couples to conceive by surgically removing an egg from the woman's ovaries and fertilising it with the man’s sperm in a laboratory.

As with IVF, PIGD involves removing eggs from a woman’s ovaries. These are fertilised using a sample of sperm taken from her partner. The fertilised embryo can be tested for sickle cell anaemia. If the results of the test are negative, the embryo can then be implanted into the woman’s womb.

PIGD is a new procedure that is only available at a number of specialist sickle cell centres. Newborn babies are now routinely screened for sickle cell anaemia. This is because the condition increases the risk of infection. Newborn babies with sickle cell anaemia are at particular risk of developing potentially dangerous infections, such as pneumonia, and they will need to receive treatment with antibiotics.

For more information about screening for sickle cell anaemia and related disorders, visit the Antenatal Screening Wales website.

If your child is diagnosed with sickle cell anaemia, you will be referred to a care team in a specialist sickle cell centre. Sickle cell centres are specialist units, usually based in large hospitals, that have a high level of experience and expertise in treating people with sickle cell anaemia.

After your child has been referred to a specialist sickle cell unit, a detailed plan outlining future medical care will be drawn up and you will be given information and support to help you manage your child’s condition.

Your care team

Sickle cell anaemia is a complex disorder that requires a number of different healthcare professionals working together as a team. Members of your care team may include:

• a paediatrician (a doctor who specialises in the treatment of children)
• a haematologist (a doctor who specialises in the treatment of blood disorders)
• a clinical psychologist
• a pharmacist
• a physiotherapist
• a social worker
• a specialist nurse

Your care plan

The care plan that is drawn up for your child will have four important objectives:

• to try to prevent sickle cell crises occurring
• to provide adequate pain relief when a crisis does occur
• to reduce the risk of serious complications occurring, such as infections and stroke
• to treat other associated symptoms of sickle cell anaemia, such as anaemia (lack of red blood cells) or priapism (persistent and painful erection)

Preventing a sickle cell crisis

Following lifestyle advice, such as drinking plenty of fluids, can help reduce the risk of experiencing a sickle cell crisis. See Self-help for sickle cell anaemia for more details.

Some children (and adults) will continue to experience episodes of pain despite their best preventative efforts. In such circumstances, a medication called hydroxyurea may be recommended.  

Hydroxycarbamide

Hydroxycarbamide is usually recommended if a child or adult has recurring episodes of a sickle cell crisis which require treatment in hospital. This is usually more than three episodes within the past 12 months.

Hydroxycarbamide was originally designed as a type of chemotherapy medication to treat cancer, but researchers found that it stimulated the production of a type of haemoglobin called foetal haemoglobin.

As the name suggests, foetal haemoglobin is a type of haemoglobin found in unborn babies. It is gradually replaced by adult haemoglobin as the child gets older.

As foetal haemoglobin is not affected by the sickle cell mutation, it is able to take over the role of adult haemoglobin to some extent, helping to reduce the risk of someone with the condition experiencing a sickle cell crisis.

Hydroxycarbamide has also proved effective in preventing acute chest syndrome (see Complications of sickle cell anaemia for more details). Therefore, the medication may also be recommended if a person has had two or more episodes of acute chest syndrome.

Hydroxycarbamide is available in capsule form and people with sickle cell anaemia are usually required to take one tablet every day.

A short-term side effect of hydroxycarbamide is that it can lower the amount of other blood cells, such as:

• White blood cells: these cells help fight infection, so having a low number of them can make a person more vulnerable to infection
• Platelets: these cells help the blood to thicken and form clots, so having a low number of them makes a person bleed and bruise more easily

As a result of this side effect, it is usually recommended that a person taking hydroxycarbamide has regular blood tests to monitor the number of blood cells. If the blood cells drop below a certain level, the dosage may need to be adjusted.

As a precaution, the use of hydroxycarbamide is not recommended during pregnancy. This is because high doses of hydroxycarbamide may increase the risks of the baby being born with birth defects. However, there is no evidence that much lower doses pose a similar risk. Sexually active men and women are advised to use a reliable method of contraception while taking hydroxycarbamide.

The use of hydroxycarbamide has also been linked to an increased risk of developing leukaemia (cancer of the white blood cells) in later life. However, as yet there is not enough evidence to assess the exact size of the risk, although it is thought to be very small.

Discuss the benefits and risks of hydroxycarbamide with your care team before you start treatment.

Pain management

Although sickle cell crises can be distressing, most episodes can be managed at home.

Over-the-counter (OTC) painkillers, such as paracetamol, can be used to control symptoms of mild to moderate pain. Always follow the dosage instructions and ensure that the recommended amount is not exceeded.

If your child’s pain is more troublesome, your GP may prescribe stronger painkillers, which usually contain a combination of paracetamol and codeine, which is a mild opiate-based medication.

Other ways that you can help to ease your child’s pain are described below.

• Ensure that your child drinks plenty of fluids. Fluids can help thin the blood and clear out the sickle cells that are clogging the blood vessels.
• Place your child in a warm bath. Ensure that the water is not too hot and do not let it get too cold because changes in temperature could trigger another crisis.
• Use a warm towel or a heated pad to gently massage the affected body part. Many pharmacists sell electrical pads that can be used for this purpose.
• Use suitable distractions. For example, reading them a story, watching a DVD or playing their favourite computer game will help to take their mind of the pain.

If your child’s pain is severe, take them to your local accident and emergency (A&E) department. If they are too unwell to travel by car, call 999 for an ambulance.

Severe pain can be treated by giving your child injections of a strong opiate-based painkiller, such as morphine.

Some parents are concerned that regular use of opiate-based painkillers will cause their child to become addicted. Your specialist or staff at the treatment clinic will carefully regulate the dosage to minimise the chances of addiction. People with sickle cell anaemia are no more likely to become addicted to opiates than anyone else.

Reducing the risk of infection

Due to the increased risk of developing serious infections, such as meningitis, it is recommended that your child takes daily doses of antibiotics, usually penicillin. In children who are allergic to penicillin, an alternative antibiotic, such as erythromycin, can be used.

Ideally, your child should take penicillin for the rest of their life or, at the very least, until they reach adulthood. The long-term use of penicillin does not pose any risks to your child’s health.

It is very important that your child’s vaccinations are up to date. As well as the routine childhood vaccinations, such as meningitis C and polio, your child will probably require some additional vaccinations due to their increased risk of infection. These may include:

• annual influenza (flu) vaccinations
• hepatitis B vaccine

As children with sickle cell anaemia often require blood transfusions, there is a small risk that they could develop blood-borne viruses, such as hepatitis B. The hepatitis B vaccination will prevent this.

Reducing the risk of a stroke

A stroke is one of the most serious complications that can arise from sickle cell anaemia. Reducing the risk of a stroke will be an important part of your child’s treatment.

Your child’s risk of a stroke can be assessed by using a test known as a Transcranial Doppler (TCD) scan. A TCD scan involves using ultrasound to measure the flow of blood through the brain. A higher than expected blood flow could be the result of the blood vessels becoming blocked and narrowed by sickled blood cells. This is a major risk factor for having a stroke.

If your child is diagnosed with sickle cell anaemia, it is recommended that they have an annual TCD scan from the age of three.

The results of the scan will highlight whether your child has a high, moderate or low risk of having a stroke. If the test results show that there is a high or moderate risk, a further TCD scan will be carried out within two months.

If the results continue to show that your child has a high risk of having a stroke, it will usually be recommended that they receive regular blood transfusions to improve the blood supply to their brain and reduce the risk of strokes.

Exactly how often your child will require a blood transfusion will depend on the result of their TCD scan and how successful the transfusions are in boosting their normal haemoglobin level. Most children require a transfusion every three to four weeks, usually up to 18 years of age.

Chelation therapy

Regular blood transfusions can help reduce your child’s risk of having a stroke by 90%, but there is an associated disadvantage. Regular blood transfusions leave an excess amount of iron in the body. This can be potentially dangerous because it can cause a number of complications, including:

• liver damage
• delayed physical and sexual development
• heart disease

This means that people who receive blood transfusions must also receive treatment to remove the excess iron from their body. This treatment is known as chelation therapy.

Deferasirox is a medication that is increasingly used during chelation therapy. It works by locking onto or binding the iron molecules in the body, before releasing them through urine or faeces (stools). Deferasirox is available in tablet form and most children need to take one tablet a day.

Common side effects of deferasirox include

• nausea
• vomiting
• abdominal pain
• diarrhoea, which is more common in younger children than older children

These side effects are usually mild and should pass once your child’s body becomes used to the medication.

Your child will require regular blood and urine tests to measure the amount of iron in their body so that the effectiveness of their chelation therapy can be assessed.

Treating associated symptoms

Anaemia

In most cases, making sure that your child eats a healthy diet should help them receive enough nutrients to compensate for the lack of healthy red blood cells.

Additional dietary supplements, such as folic acid (which helps stimulate the production of red blood cells) are usually only required if your child has a restricted diet, such as a vegetarian or vegan diet.

Never give your child iron supplements without first consulting your GP.

The type of anaemia associated with sickle cell is not due to an iron deficiency and increasing your child’s levels of iron could be potentially dangerous, particularly if they have been receiving blood transfusions.

A sudden worsening of your child’s anaemia, such as an aplastic crisis, will usually require a blood transfusion so that the amount of red blood cells can be increased to a healthy level.

Gallstones

If your child develops repeated symptoms of pain due to gallstones, it is usually recommended that they have their gallbladder surgically removed. This type of operation is known as a cholecystectomy.

Avascular necrosis

Mild to moderate cases of avascular necrosis can be treated with painkillers to relieve the pain and a type of medication, called bisphosphonates, to prevent any further loss of bone tissue.

More severe cases may require referral to an orthopaedic surgeon (a surgeon who specialises in treating bone and joint conditions) as surgery may be required to repair damage to the bone.

Leg ulcer

A leg ulcer can be treated by cleaning out the ulcer with sterile (germ-free) water and dressing the ulcer with a bandage. See Leg ulcer treatment for more information about how leg ulcers are treated. 

Delayed growth

Most children with sickle cell anaemia should ‘catch up’ on growth and reach a normal height by their early adulthood.

In more severe cases of delayed growth, zinc supplements may be recommended. Zinc is a metal that plays an important role in stimulating bone and muscle growth.

If your child does not show any physical signs of puberty by the time they have reached 14 or 15 years of age, a referral to an endocrinologist is recommended. An endocrinologist is a doctor who specialises in treating hormonal conditions.

The endocrinologist may prescribe a short course of hormonal medication to help trigger the onset of puberty.

Priapism

If your child develops the symptoms of priapism (a persistent and painful erection of the penis), carry out some self-care techniques to try to relieve symptoms:

• Make sure your child drinks plenty of fluids.
• Encourage your child to urinate regularly.
• Use over-the-counter (OTC) painkillers to help relieve pain.
• A warm shower or bath can help encourage blood circulation.

If these techniques fail to control your child’s symptoms of priapism and an episode lasts for more than two hours, take your child to the nearest accident and emergency (A&E) department.

Available treatment options include medication to help stimulate blood circulation and a needle to drain away the blood from the penis.

Bone marrow transplant

The only current cure for sickle cell anaemia is a bone marrow transplant. The procedure involves replacing the affected bone marrow with bone marrow donated from someone who does not have sickle cell anaemia. After a bone marrow transplant, the new bone marrow will begin to produce healthy blood cells.

There are some significant risks involved in having a bone marrow transplant. For example, sometimes the new bone marrow will start to produce cells that attack parts of your child’s body. This is known as graft-versus-host disease (GVHD).

GVHD can affect many parts of the body, although the eyes, skin, stomach and intestines are most commonly affected. Symptoms include:

• a rash
• nausea
• weight loss
• irritation of the eyes
• jaundice (yellowing of the skin and whites of the eyes)

Other risks related to bone marrow transplants include an increased chance of:

• strokes
• seizures (fits)
• tumours

As a result of these risks, it is estimated that 1 in 10 people who receive bone marrow will die due to complications that arise from the procedure. Due to the risk, a bone marrow transplant is only usually recommended if:

• your child is under 17 years of age (children often have less organ damage from sickle cell disease than adults, which improves their chances of survival)
• your child has a brother or sister with healthy bone marrow (a close family connection reduces the risks of developing GVHD)
• your child’s symptoms are severe enough to be life threatening, for example if they have had one or more episodes of acute chest syndrome.

As sickle cell anaemia can block the flow of oxygen to parts of your child’s body, it can cause a number of serious complications. These are described below.

Stroke

A stroke is one of the most serious complications of sickle cell anaemia. It can happen when the sickle cells block the flow of oxygen to your child’s brain.

The symptoms of a stroke in children with sickle cell anaemia include:

• weakness and paralysis on one side of the body
• seizures (fits)
• sudden difficulty with speech
• disturbed vision
• changes in mental state, such as confusion or a sudden loss of emotional control

If you suspect that your child has had a stroke, dial 999 immediately and ask for an ambulance.

Some children with sickle cell anaemia may experience a transient ischaemic attack (TIA), or ‘mini-stroke’. A TIA occurs when the supply of blood to the brain is temporarily interrupted.

The symptoms of a TIA are similar to those of a stroke, but they only last for a few minutes to a few hours before they completely disappear. However, do not ignore a TIA because it is a serious warning sign that there is a problem with the brain’s blood supply.

If your child has had a TIA, contact your GP, local hospital or out-of-hours service immediately to arrange for a specialist assessment.

Strokes can be treated by blood transfusions. Blood transfusions are not effective for treating strokes in adults who do not have sickle cell anaemia because the causes are usually different, such as a blood clot or burst artery.

Once your child’s condition has stabilised, it is usually recommended that they continue to receive regular blood transfusions to reduce the risk of further strokes.

Acute chest syndrome

Acute chest syndrome is a life-threatening lung condition. The exact cause of acute chest syndrome is unknown, although it is thought that an infection in the lungs, which are already damaged by sickle cell anaemia, can cause problems with the air circulating in the lungs.

The symptoms of acute chest syndrome include:

• high temperature (fever) of 38C (100.4F) or above
• chest pain
• cough
• breathing difficulties
• breathing much more quickly than normal

If you think your child has developed acute chest syndrome, dial 999 immediately and ask for an ambulance.

Acute chest syndrome requires emergency medical treatment with antibiotics, blood transfusions, oxygen and intravenous fluids (where liquids are pumped directly into your child’s veins to help rehydrate their body).

Splenic sequestration crisis

Splenic sequestration crisis (SCC) is a complication that can affect younger children with sickle cell anaemia. It usually affects children between the age of six months and three years.

SSC occurs when the sickled red blood cells become trapped inside the spleen. This causes the spleen to swell and at the same time leads to a dangerous drop in the number of red blood cells in the rest of the body.

The symptoms of SSC include:

• unusually pale skin
• fatigue
• shortness of breath
• irritability
• rapid heartbeat (tachycardia)
• abdominal pain, usually in the left side of your child’s abdomen
• swelling of the spleen (you should be able to check for this by gently touching the upper left side of your child’s abdomen, just underneath their rib cage)

If you think your child has experienced SCC, immediately contact your GP or a member of their sickle cell care team for advice. If this is not possible, call your local out-of-hours service or NHS Direct Wales (0845 46 47).

Some episodes of SSC are minor and resolve themselves without the need for treatment. However, more severe episodes will require hospital admission for treatment with a blood transfusion.

Vision problems

In cases of sickle cell anaemia, the blood vessels that lead to the eyes can get blocked by sickled cells. This can cause damage to the retina, which is known a retinopathy. The retina is a light-sensitive layer of cells that processes the light that comes into the eye and sends signals to the brain.

The symptoms of retinopathy can include:

• floaters (coloured spots that ‘float’ in your field of vision)
• blurred vision
• vision that is blocked by patches or streaks
• reduced night vision
• most seriously, sudden vision loss

If your child complains of any deterioration in their vision, contact your sickle cell care team for advice.

Retinopathy can be treated using laser surgery to repair damage to the blood vessels and retina. It is recommended that your child has regular eye examinations (at least once a year).

Depression

Living with a condition that is as unpredictable as sickle cell anaemia can cause considerable feelings of anxiety and stress, which can often trigger an episode of depression.

Research has found that around half of people living with sickle cell anaemia will experience at least one episode of depression during their life.

It can often be difficult to spot the signs of depression in children, particularly in teenagers, because they are often reluctant to talk about their feelings with their parents.

Signs that your child may be depressed include:

• no longer showing interest or taking pleasure in activities that they used to enjoy
• an inability to make or keep friends
• lack of energy
• problems sleeping or, alternatively, sleeping much more than usual
• changes in their diet, either eating much more or much less than usual,
• a sudden worsening of behaviour, such as getting into trouble at school or frequent rule breaking at home
• a general lack of enjoyment in their day-to-day life

If you are concerned that your child may be depressed, encourage them to talk about their feelings in a calm, non-judgemental way while stressing that additional help and support is available if they need it.

Mild to moderate depression in children and young people is often treated with talking therapies such as cognitive behavioural therapy (CBT). CBT is based on the principle that the way a person feels is partly dependent on the way that they think about things. It teaches children and young people to behave in ways that challenge negative thoughts, for example being active to challenge feelings of hopelessness.

More severe cases of depression are usually treated using a combination of talking therapies, such as CBT, and antidepressant medications, such as fluoxetine.

Reducing the risk of a sickle cell crisis

In addition to the medication hydroxyurea, there are a number of self-care techniques that you should encourage your child to use to reduce their risk of having a sickle cell crisis. These are described below.

Drink plenty of water

It is particularly important to drink fluids in hot weather because dehydration increases the likelihood that sickle cells will form.

The exact amount of water that your child will need each day depends on their weight, although older children who weigh more than 20 kilograms (3 stone) should drink at least a litre of water a day. Your child’s sickle care team can give you more detailed advice about your child’s recommended fluid intake.

Exercise regularly

Your child should take regular exercise, but should avoid becoming too tired or seriously out of breath. Your GP can give you further advice and recommend an appropriate level of exercise for your child.

Eat a healthy, balanced diet

Eating a healthy diet will encourage your child’s growth and development, and strengthen their immune system, which will help reduce their risk of developing infections.

A low-fat, high-fibre diet is recommended, including plenty of fresh fruit and vegetables (five portions a day) and whole grains.

The same advice applies to adults with sickle cell anaemia who, in addition, should:

• limit the amount of alcohol they drink: the recommended daily limits are 3-4 units for men and 2-3 units for women (a unit of alcohol is equal to about half a pint of normal strength lager, a 25ml measure of spirits or a small glass of wine)
• avoid smoking: for advice and encouragement to stop smoking, call the Smokers helpline Wales on 0800 169 0 169.
• As well as making healthy changes to your diet and lifestyle, you should also avoid:
• extremes of temperature: exposure to extreme heat or cold can trigger the formation of sickle cells
• high altitude areas: the lack of oxygen at high altitudes may trigger a crisis
• stress: stressful events have been shown to trigger a crisis

Learning relaxation techniques, talking about your problems with your family and friends, or joining a support group have all been shown to reduce stress in people who are living with sickle cell anaemia.

Flying with sickle cell anaemia

Flying in commercial airliners should not be a problem for people with sickle cell anaemia because the aeroplanes are completely pressurised. However, make sure that you drink plenty of non-alcoholic fluid to ensure that you do not become dehydrated.

Smaller aeroplanes, military planes and helicopters may not be pressurised and flying in them could cause a sickle cell crisis. Before flying, check with the cabin crew or other members of the aircrew that the aircraft is completely pressurised.