What is sickle cell anaemia?

Genetics

• Sickle cell anaemia is caused by a mutation in a gene called haemoglobin beta (HBB), located on chromosome 11.
• It is a recessive genetic disease, which means that both copies of the gene must contain the mutation for a person to have sickle cell anaemia.
• If an individual has just one copy of the mutated gene they are said to be a carrier of the sickle cell trait.
• If both parents are carriers there is a chance their child could be born with sickle cell anaemia.

Biology

• The HBB gene codes for haemoglobin, a protein in red blood cells that carries oxygen around the body .
• A mutation in HBB results in a change in one of the bases in the DNA sequence from an A to a T.
• This then changes the amino acid in the haemoglobin protein from glutamic acid to valine.
• This causes the body to produce a new form of haemoglobin called HbS, which behaves very differently to regular haemoglobin (HbA).
• HbS causes the red blood cells to develop abnormally and become sickle-shaped (rather than the usual doughnut shape), harder and less flexible.
• This means that they can become stuck in the blood vessels, causing blockages.

Illustration showing the difference between normal red blood cells and sickle red blood cells.
Image credit: Genome Research Limited

Symptoms

• The symptoms of sickle cell anaemia vary considerably from person to person.
• Pain develops when sickle-shaped red blood cells block the flow of blood to the chest, abdomen and joints.
• These spells of pain are called ‘sickle cell crisis’ and can last anything from a few minutes to several months.
• Symptoms can have a significant impact on quality of life and can lead to life-threatening complications such as:
  • stroke: where the supply of blood to the brain becomes blocked.
  • acute chest syndrome: where the lungs suddenly lose their ability to breathe in oxygen as a result of sickle cells blocking blood vessels in the lungs.
  • increased risk of infection: sickle cell anaemia can damage the spleen, a key organ involved in fighting infection.
  • pulmonary hypertension: where sickle-shaped red blood cells block the flow of blood from the heart to the lungs causing the blood pressure in these vessels to become dangerously high.
• Sudden deterioration may be characterised by:
  • high body temperature of 38˚C or above
  • severe pain that cannot be controlled with paracetamol or ibuprofen
  • difficulty breathing.
• Methods to deal with sickle cell anaemia have improved dramatically in recent years, so serious complications rarely occur and people now live much longer than they used to.
• 40 years ago, few people lived past their teenage years and many died before the age of two years. The main cause of death was bacterial infection.
• Now, most affected people are expected to live to about 40 or 50 years old. The main causes of death are infections and stroke.

Diagnosis

• Sickle cell anaemia is diagnosed using a blood test which detects the presence of the abnormal HbS haemoglobin in the red blood cells.
• In children the blood is taken by pricking a finger or heel.
• In adults the blood is drawn from a vein in the arm.
• The blood sample is analysed to see if the abnormal HbS haemoglobin (rather than normal HbA haemoglobin) is present.

Treatment

• Most treatments aim to treat the individual symptoms of sickle cell such as anaemia.
• Treatment plans require a number of different healthcare professionals working together, such as haematologists (specialists in blood disorders), clinical psychologists, social workers and physiotherapists who can help patients with pain monitoring and relief.
• Regular blood transfusions can help reduce the risk of complications, such as stroke, by up to 90 per cent.
• However, chelation therapy may need to be given after transfusion to remove excess iron from the patient’s body. This excess iron can lead to complications including liver cancer, diabetes and infections.
• Daily antibiotics, such as penicillin, are often given to help protect against serious infections in children aged under five years.
• Pain relief is provided to reduce the pain associated with sickle cell crisis.
• Lifestyle advice, such as drinking plenty of fluids, is given to help reduce the risk of sickle cell crisis.
• If individuals continue to experience pain, a medication called hydroxycarbamide may be offered, to be taken once a day.
  • This drug works by stimulating the body to produce another type of haemoglobin, called foetal haemoglobin.
  • Foetal haemoglobin is not affected by the mutation that causes sickle cell anaemia.
  • Foetal haemoglobin can substitute for the adult haemoglobin to carry oxygen around the body and help reduce the risk of a sickle cell crisis occurring.
• The risk of an individual developing complications can also be assessed to help prevent them occurring.
  • A child’s risk of a stroke can be assessed using a test known as a Transcranial Doppler scan that measures the rate of blood flow in blood vessels in the head and neck, which supply blood to the brain.
  • If the arteries are narrow, which can increase the risk of having a stroke in the future, blood travels faster and makes a high pitched noise that can be detected by the scanner.
• Blood and bone marrow stem cell transplants may offer a cure for a small number of people.

Screening

• In the UK, all pregnant women are asked to answer a questionnaire to assess their risk of carrying a baby with sickle cell anaemia.
• Pregnant women may also be offered a blood test to find out if they are a carrier of the faulty HBB gene that causes sickle cell anaemia.
• If they are found to be a carrier, the baby’s father is then offered a blood test too.
• If both parents are carriers there is a chance the baby will be born with sickle cell anaemia.
• All babies in the UK are tested for sickle cell anaemia after birth through the heel-prick newborn screening test.
• Anyone from at risk groups having a general anaesthetic is tested for sickle cell anaemia. This is because general anaesthetic reduces the amount of oxygen in the blood, which could be dangerous for someone with the condition.