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Sickle-cell anaemia

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Sickle-cell anaemia


  


Introduction 

Sickle cell anaemia is a serious inherited blood disorder where the red blood cells, which carry oxygen around the body, develop abnormally.

The disorder mainly affects people of African, Caribbean, Middle Eastern, Eastern Mediterranean and Asian origin. In the UK, sickle cell disorders are most commonly seen in African and Caribbean people.

Normal red blood cells are flexible and disc-shaped, but in sickle cell anaemia they can can become rigid and shaped like a crescent (or sickle).

The sickle-shaped cells contain defective haemoglobin, the iron-rich protein that enables red blood cells to carry oxygen from your lungs to the rest of the body.

The abnormal cells are also unable to move around as easily as normal shaped cells and can block blood vessels, resulting in tissue and organ damage and episodes of severe pain.

Such episodes are known as a sickle cell crisis or a vaso-occlusive crisis. They can last from a few minutes to several months, although on average most last five to seven days.

The abnormal blood cells also have a shorter lifespan and aren't replaced as quickly as normal blood cells. This leads to a shortage of red blood cells, known as anaemia.

Symptoms of anaemia include lethargy (a lack of energy), tiredness and breathlessness, particularly after exercise.

What causes sickle cell anaemia?

Sickle cell anaemia is caused by a mutation (an abnormal change) in the gene that instructs the body to produce haemoglobin.

The sickle cell gene is inherited (passed on between family members). To get sickle cell anaemia you have to inherit the defective gene from both parents.

If you only inherit the gene from one parent, you have what's known as the sickle cell trait. It's likely that your blood will contain some sickle cells, but you'll be able to produce normal haemoglobin and won't usually experience symptoms. However, you'll be a carrier of sickle cell anaemia and may pass the abnormal gene on to your children.

In England, about 250,000 people are thought to have the sickle cell trait, with those of African-Caribbean origin primarily affected.

If two people with the sickle cell trait have a child, there's a one in four chance that the child will be born with sickle cell anaemia.

Diagnosing and screening for sickle cell anaemia

Sickle cell anaemia can be diagnosed using a blood test. The blood is checked for defective haemoglobin.

A small level of defective haemoglobin would indicate that a person has the sickle cell trait but not sickle cell anaemia. A high level would indicate sickle cell anaemia.

Antenatal screening (screening carried out during pregnancy) is used to check for inherited disorders, such as sickle cell anaemia.

Antenatal screening for the sickle cell trait is available in areas where the condition is most common, such as where there are large Afro-Caribbean communities.

In parts of the country where sickle cell anaemia is uncommon, a questionnaire that focuses on family origin is used to assess the risk of sickle cell disorders.

All babies born in the UK are tested for sickle cell anaemia as part of the heel prick newborn screening test that's carried out by the midwife.

People in high risk groups should be tested for the sickle cell trait or thalassaemia (see box) before having a general anaesthetic. This is because this type of anaesthesia temporarily lowers the amount of oxygen in the blood, which could be dangerous for someone with these blood conditions.

Treating sickle cell anaemia

If your child is diagnosed with sickle cell anaemia, they'll be referred to a specialist sickle cell centre.

Sickle cell centres are specialist units usually based in large hospitals. The staff at these units have a high level of expertise in treating people with sickle cell anaemia.

A detailed plan outlining future medical care will be drawn up and you'll be given information and support to help manage your child’s condition.

Following simple lifestyle advice, such as drinking plenty of fluids, can help reduce the risk of experiencing a sickle cell crisis. 

Sometimes, a person with sickle cell anaemia will continue to experience pain despite taking preventative measures. In such cases, a medication called hydroxycarbamide may be recommended.

Complications of sickle cell anaemia

The symptoms of sickle cell anaemia can have a significant impact on a person's quality of life. If complications develop, these can be very serious. Possible complications include:


stroke – where the blood supply to part of the brain is cut off

increased vulnerability to infection

acute chest syndrome – where the lungs suddenly lose their ability to breathe in oxygen (often the result of an infection)

pulmonary hypertension – where the blood pressure inside the blood vessels that connect the heart to the lungs becomes dangerously high


However, following improvements in preventative treatment, many complications associated with sickle cell anaemia can be avoided.

The life expectancy of a person with sickle cell disease has increased significantly over recent decades. A person with the condition can expect to live into their late 40s or early 50s.

When to seek urgent medical advice

Because of the risk of potentially life-threatening complications, it's important to look out for any signs or symptoms that the health of a person with sickle cell anaemia has suddenly deteriorated. These include:


a high temperature (fever) of 38C (100.4F) or above

breathing difficulties

severe pain that develops during a sickle cell crisis that can't be controlled using over-the-counter painkillers, such as paracetamol or ibuprofen




 


Sickle cell anaemia: Pamela's story

Pamela, 18, was born with sickle cell anaemia, a genetic blood disorder. She describes how to cope with the disease on a daily basis, and explains why it is important to raise awareness of the condition.


Media last reviewed: 28/08/2013

Next review due: 28/08/2015



Similar inherited blood disorders


Thalassaemia:
– affects production of haemoglobin (protein that transports oxygen in the blood) 
– an estimated 1,000 people in the UK have it 
– most affected people are of Mediterranean, Middle Eastern and South Asian origin

Haemoglobin C disease:
– thought to affect about one in 1,000 people of African and Caribbean origin
– much less serious than sickle cell anaemia
– usually causes mild anaemia and sometimes joint pain


Symptoms of sickle cell anaemia 

Sickle cell anaemia can cause a wide range of symptoms, although not everyone with the condition will experience all of the symptoms.

Sickle cell crisis

Episodes of pain during a sickle cell crisis are one of the most common and upsetting symptoms of the condition.

A sickle cell crisis (also known as a vaso-occlusive episode or VOE) is triggered when the abnormal blood cells block the small blood vessels that supply the body’s tissues.

This damages the cells in the affected tissue, resulting in the tissue becoming swollen, which irritates nearby nerve endings.

During a sickle cell crisis, younger children may develop painful swelling in their hands or feet. This is often the first noticeable symptom.

As a child gets older, pain can occur in any area of the body. However, the most commonly affected areas are the:


ribs

spine

pelvis

abdomen

sternum (breastbone)

long bones in the legs and arms


People with sickle cell anaemia describe the pain as aching, throbbing, sharp and shooting, penetrating or burning.

The pain can be severe and episodes can last from a few minutes to several weeks, with an average duration of around five to seven days.

Children may experience one or two, or as many as 14, episodes a year.

A sickle cell crisis can often occur for no apparent reason, but there are often certain triggers such as:


sudden changes in body temperature which can either be from an infection or a change in the outside environment

dehydration – when the body loses more fluid than it takes in

a sudden shortage of oxygen as a result of exercise, sudden exertion or stress


Potential triggers in older children and adults with sickle cell anaemia include:


alcohol

cigarettes

illegal drugs, such as cannabis and cocaine


It's important to learn what triggers a painful episode so that they can be avoided.

Anaemia

Anaemia, where the amount of haemoglobin in the blood is lower than normal or there are less red blood cells than normal, is a common symptom of sickle cell anaemia. The abnormal cells have a shorter lifespan and aren't replaced quickly enough.

Symptoms include:


fatigue – extreme tiredness and a general lack of energy 

shortness of breath 

palpitations (irregular heartbeat)


Children are often able to compensate for the lack of red blood cells by an increase in heartbeat, although symptoms of fatigue may persist. This can make it difficult to participate in physical activities such as sport.

Aplastic crisis

A more serious type of anaemia called aplastic crisis can occur if your child develops a common childhood infection known as slapped cheek syndrome or parvovirus B19.

The combination of infection and pre-existing anaemia can cause a sharp and sudden drop in the number of red blood cells inside your child’s body.

Symptoms of an aplastic crisis include:


very pale skin

fatigue

headache

fever (high temperature) of 38C (100.4F) or above

tachycardia (rapid heartbeat)

dizziness

fainting


Vulnerability to infection

Children with sickle cell anaemia are more vulnerable to infection, particularly those younger than three years. This is because the abnormal blood cells can disrupt the normal functions of the spleen.

The spleen is an organ found in the abdomen (in the lower left side of the body, behind the stomach). It plays an important role in filtering harmful bacteria and viruses from the blood.

Children with sickle cell anaemia are particularly vulnerable to three types of infection:


pneumonia – a lung infection

osteomyelitis – an infection that develops inside a bone

meningitis – an infection of the lining of the brain


As younger children with sickle cell anaemia are at increased risk of developing an infection, daily doses of antibiotics are often recommended as a precaution.

Other vaccinations may also be recommended, such as the Pneumovax, which protects against some types of bacteria that can cause pneumonia; the meningococcal vaccines, which protect against meningitis and septicaemia; and the annual flu vaccinations.

Jaundice and gallstones

Jaundice (yellowing of the skin and whites of the eyes) is a common symptom of sickle cell anaemia. It occurs because the rapid breakdown of abnormal red blood cells leads to a build-up of a waste product in the body called bilirubin.

The build-up of bilirubin often leads to the formation of small crystals called gallstones. Most gallstones don't cause symptoms but they can occasionally block the bile duct, which drains bile from the liver into the bowel. This can trigger jaundice.

More commonly, a gallstone can get stuck in the gallbladder, causing it to become swollen and leading to abdominal pain and nausea.

Avascular necrosis

Avascular necrosis (AVN) is the loss of bone tissue due to a restriction of blood supply.

In children with sickle cell anaemia, AVN usually affects the hip. The first sign can be a limp or pain in the groin. AVN can cause persistent hip pain that can last for several months. In severe cases, it may be necessary for your child to avoid putting weight on the affected leg and they may need to use crutches or a wheelchair.

Less commonly, AVN can affect the shoulder joint or elbow.

Leg ulcer

A leg ulcer is a painful, open sore that develops on the lower leg, usually close to the ankle. Leg ulcers often develop after a skin infection or injury, such as a cut or puncture wound.

Children with sickle cell anaemia have an increased risk of developing leg ulcers. This is because the lack of normal red blood cells means that their leg doesn't receive the nutrients it needs to keep the skin and surrounding tissue healthy.

Delayed growth

Red blood cells provide the oxygen required for physical development. If your child has sickle cell anaemia, it's likely they'll experience delayed growth compared with other children.

Many children with sickle cell anaemia will also experience puberty at a later stage (around 13-14 years of age for girls and 13½-14½ years of age for boys).

The average age of puberty in children who don't have sickle cell anaemia is 11 years of age for girls and 12 years of age for boys.

Priapism

Priapism is the medical term that describes a persistent and painful erection of the penis. Episodes of priapism can sometimes last for several hours.

Priapism can affect teenage boys and men with sickle cell anaemia because the abnormal blood cells can cause blood to become trapped in the penis.

Priapism doesn't usually develop as a result of sexual stimulation and it can often occur for no apparent reason, usually during a sickle cell crisis.

Teenage boys may be too embarrassed to mention that they're experiencing priapism.

If you have a teenage son with sickle cell anaemia, it's very important that you make them aware of the importance of seeking immediate treatment for priapism.

This is because episodes of priapism that last for more than two hours can permanently damage the penis and may affect your son's ability to obtain an erection in the future.

When to seek urgent medical advice

Because of the risk of the potentially life-threatening complications associated with sickle cell anaemia, it's important that you're aware of any signs or symptoms that your child’s health has suddenly worsened.

Signs and symptoms to look out for are:


fever (high temperature) of 38C (100.4F) or above

severe pain that develops during a sickle cell crisis that can't be controlled using over-the-counter painkillers

breathing difficulties

severe abdominal pain or swelling

severe headache, stiff neck or dizziness

changes in mental state, such as appearing confused or drowsy

episodes of priapism (see above) that last longer than two hours

seizures (fits)


Contact your GP immediately if your child develops any of the above symptoms. If this isn't possible, take your child to your local accident and emergency (A&E) department.

You can take them by car if they are well enough to travel. However, if this isn't the case, dial 999 to request an ambulance.

It's very important when requesting an ambulance or visiting A&E that you inform all ambulance, medical and nursing staff that your child has sickle cell anaemia. This will ensure that they're aware of the potentially serious nature of your child’s condition.

Causes of sickle cell anaemia 

Sickle cell anaemia is caused by a genetic mutation that affects the normal development of haemoglobin.

A genetic mutation is a permanent change in the normal pattern of genetic information inside all living cells. This results in one or more of the body's processes not working properly.

Haemoglobin

Haemoglobin is an iron-rich protein found in red blood cells. It enables the blood cells to carry oxygen from your lungs to the rest of your body.

As blood passes through your lungs, the haemoglobin pulls in oxygen and at the same time releases carbon dioxide. This process is known as oxygenation. 

After leaving your lungs, the haemoglobin delivers oxygen to the body’s tissue and removes excess carbon dioxide to take back to your lungs. This process is called deoxygenation.

During deoxygenation, healthy haemoglobin molecules smoothly rearrange themselves into a different shape. However, in sickle cell anaemia, the smooth rearrangement doesn't occur because of the mutated gene.

Instead, the haemoglobin inside blood cells clumps together into solid structures. The clumping distorts the normal shape of the red blood cells, causing them to take on a rigid, sickle shape.

The genetics of sickle cell anaemia

Genes come in pairs. You receive one copy of a gene from your mother and one copy from your father.

To have sickle cell anaemia, you would need to receive a pair of mutated genes – one mutated gene from your mother and one from your father.

If you only receive one mutated gene, you won't have sickle cell anaemia, but you'll be a carrier of the sickle cell gene. This is often referred to as having the sickle cell trait. It's estimated that one in 10 people of African or Caribbean descent has the sickle cell trait.

If you're a carrier, you won't usually notice any obvious symptoms unless you're somewhere where there's a low amount of oxygen in the air, such as on top of a mountain.

If both you and your partner have the sickle cell trait, there's a risk that any children you have will inherit a pair of mutated genes and develop sickle cell anaemia.

The chances of sickle cell anaemia being passed on are:


a one in four chance that your baby will receive a pair of normal haemoglobin genes

a one in two chance that your baby will receive one normal gene and one mutated gene and be a carrier of the sickle cell gene 

a one in four chance that your baby will receive a pair of mutated genes and have sickle cell anaemia


If one partner has the sickle cell trait and the other partner has normal haemoglobin, their baby won't develop sickle cell anaemia. However, there's a one in two chance that the baby will have the sickle cell trait.

If you have sickle cell anaemia and your partner has the sickle cell trait (or vice versa), any baby you conceive will have a one in two chance of developing sickle cell anaemia. This is because they'll definitely receive a mutated gene from you, and there's a one in two chance they'll also receive a mutated gene from your partner.






A crescent- or sickle-shaped blood cell (left) alongside three normal shaped red blood cells

 

Diagnosing and screening for sickle cell anaemia 

Sickle cell anaemia can be diagnosed using a blood test to check for defective haemoglobin.

A small amount of defective haemoglobin would suggest that you have the sickle cell trait (you're a carrier of the sickle cell gene), but don't have sickle cell anaemia. A high level of defective haemoglobin would indicate that you have sickle cell anaemia.

 

Hydroxycarbamide

Hydroxycarbamide is usually recommended if a person with sickle cell anaemia has recurring episodes of a sickle cell crisis. This is usually more than six episodes in the past 12 months.

Hydroxycarbamide may also be recommended if:


testing shows that a person is at increased risk of having a stroke (see below)

a person has severe symptoms of anaemia that aren't responding to other treatments


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

Foetal haemoglobin is found in unborn babies. It's gradually replaced by adult haemoglobin as a child gets older.

As foetal haemoglobin isn't affected by the sickle cell mutation, it's able to take over the role of adult haemoglobin to some extent. This helps reduce the risk of someone with the condition experiencing a sickle cell crisis.

Hydroxycarbamide has also proved effective in preventing acute chest syndrome (a life-threatening lung condition). 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 including:


white blood cells – these cells help fight infection; having a low number of them can make you more vulnerable to infection

platelets – these cells help the blood to thicken and form clots; having a low number of them can make you bleed and bruise more easily


If you're taking hydroxycarbamide, regular blood tests will usually be recommended to monitor your blood cells. If your blood cells drop below a certain level, the dosage may need to be adjusted.

Other side effects can include:


diarrhoea

constipation

feeling sick


As a precaution, the use of hydroxycarbamide isn't recommended during pregnancy. This is because high doses of the medication may increase the risks of the baby being born with birth defects.

There's no evidence that much lower doses pose a similar risk. However, as a precaution, 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, this risk is thought to be extremely small.

In most cases the potential benefits of using hydroxycarbamide outweigh the risks, but you should discuss any concerns that you have with your child’s (or your) care team.

 

Pain management

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

Over-the-counter painkillers, such as paracetamol, can be used to control symptoms of mild pain. Always follow the dosage instructions and ensure the recommended amount isn't exceeded.

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

Other ways of easing your child’s pain are described below.


Ensure that your child has plenty to drink. Fluids help thin the blood and clear out the sickle cells that are clogging the blood vessels.

Place your child in a warm bath. Make sure that the water isn't too hot and don't 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 film or playing their favourite computer game will help to take their mind off the pain.


If your child’s pain is severe, take them to your nearest accident and emergency (A&E) department. If they're too unwell to travel by car, dial 999 to request an ambulance.

Hospital treatment for a painful episode is usually only needed if the pain is uncontrolled or there’s no access to analgesia (pain relieving medication).

Once your child has been admitted to hospital, they may need to stay in for several days until their pain has been effectively controlled.

This can usually be achieved by trying a number of different pain relief medications and carrying out regular assessments to help determine how effective each medication has been.

The treatment should take into account the needs and preferences of the individual and, where possible, they or you should be given the opportunity to make informed decisions about their treatment and care.

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's recommended that children take daily doses of antibiotics, usually penicillin. If your child is 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 won't pose any risks to your child’s health.

It's vitally important that your child’s vaccinations are up to date. As well as the routine childhood vaccinations, such as meningitis C and tetanus, your child will probably need some additional vaccinations, such as an annual flu vaccination and the hepatitis B vaccine. 

As children with sickle cell anaemia often require blood transfusions, there's 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 of 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 using a test known as a transcranial doppler (TCD) scan. The scan uses ultrasound to measure the blood flow through the brain. A fast blood flow could be caused by narrowed blood vessels that are clogged by abnormal red blood cells. This is a major risk factor for having a stroke.

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

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

If the results of the second scan still indicate a high stroke risk, regular blood transfusions to improve blood supply to the brain will usually be

Chelation therapy

Regular blood transfusions can help reduce your child’s risk of having a stroke by 90%. However, blood transfusions can also leave excess iron in the body.

This can cause a number of potentially dangerous complications, including liver damage, delayed physical and sexual development and heart disease.

As a result, people who have regular blood transfusions must also be treated to remove excess iron from their body. This treatment is known as chelation therapy.

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

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

Treating associated symptoms

 

Anaemia

In most cases, if your child eats a healthy, balanced diet they should get enough nutrients to compensate for their lack of healthy red blood cells.

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 consulting your GP first.

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

A sudden worsening of your child’s anaemia, such as an aplastic crisis (an abnormal decrease in immature red blood cells), may require a blood transfusion to restore the number of red blood cells to a healthy level.

Gallstones

If your child has pain due to gallstones, it's usually recommended they have their gallbladder surgically removed. This type of operation is known as a cholecystectomy.

 

Depression

Living with a condition as unpredictable as sickle cell anaemia can cause anxiety and stress, which often leads to depression.

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

It can be difficult to spot depression in children, particularly in teenagers, because they're often reluctant to talk about their feelings with their parents.

Signs your child may be depressed include:


no longer showing interest or taking pleasure in activities 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 day-to-day life


If you're concerned that your child may be depressed, encourage them to talk about their feelings in a calm, non-judgemental way.

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 they think about things. It teaches children and young people to behave in ways that challenge negative thoughts – for example, confronting feelings of hopelessness.

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


Sickle-cell-anaemia