Unravelling Sickle Cell Anaemia

✍🏽 Monica Neves | BSc (Hons) Biomedical Science graduate from the Uni of the West of Scotland

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What is sickle cell anaemia?🩸

Sickle cell anaemia is an inherited blood condition resulting from a genetic mutation in both copies of haemoglobin beta (HBB) gene.

Molecular structure of haemoglobin, two beta globins and two alpha globins (produced using Biorender)

HBB gene contains the instructions to make beta globins, two of the subunits that make up haemoglobin A. Haemoglobin A is a larger protein found in red blood cells, responsible for transporting oxygen from the lungs throughout the body and taking carbon dioxide from the body's tissues back to the lungs. However, in sickle cell anaemia, an abnormal variant of haemoglobin A is produced, haemoglobin S.

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What is the difference between sickled red blood cells and normal red blood cells? 🌙

Haemoglobin S affects the structure and function of red blood cells.

Red blood cell versus sickled red blood cell (produced using Biorender)

Normal red blood cells present a biconcave disk formation meaning they are thinner in the centre. This feature provides them with extensive flexibility allowing them to navigate freely through narrow blood vessels. They produce haemoglobin A and have a life span of 120 days.

Whereas, sickled red blood cells have a crescent moon-like shape. These cells are rigid and tend to stick to the walls of blood vessels, disrupting blood flow. In severe cases, this results in vaso-occlusive crises, a painful sensation that, over time, can result in organ damage. Sickled cells have a shorter life span, ranging between 10 and 20 days.

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How is sickle cell anaemia inherited? 🧬

Sickle cell anaemia is inherited when both parents have sickle cell trait (they are carriers) or if at least one of the parents has the disease.

Carriers inherit only one copy of the sickle cell gene; as such, they do not have the disease but are capable of passing it to their children.

• If both parents have sickle cell anaemia, their children will inherit the disease.

• If one parent is a carrier and the other has sickle cell anaemia, there is a 50% chance that each of their children will inherit the disease.

• In the case where both parents are carriers, there is a 25% chance that each of their children will have the disease.

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Who does sickle cell anaemia affect? 👶🏾

Sickle cell anaemia is more common in individuals of African and Caribbean ethnic backgrounds in the United Kingdom.

The disease can also be found in Middle Eastern, Eastern Mediterranean, and Asian people.

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What are the symptoms and signs of sickle cell anaemia? 🥱

Symptoms and signs of sickle cell anaemia may include:

• Periodic episodes of severe pain in the arms, legs and back (pain crises)

• Yellowing of the skin or the whites of the eyes (jaundice)

• Low red blood cell count and reduced haemoglobin levels (anaemia)

• Frequent infections

• Extreme fatigue

• Severe and painful swelling of hands and feet (dactylitis)

Symptoms typically become more apparent after the first year of life when foetal haemoglobin (haemoglobin F) is replaced with the adult haemoglobin. Unlike adult haemoglobin, the foetal version has two gamma subunits instead of the two beta subunits, which is why symptoms are usually not present.

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How is sickle cell anaemia diagnosed? 💉

The NHS offers neonatal sickle cell disease screening as part of the newborn blood spot screening programme.

A blood sample is taken from the heel of 5-day-old babies, with four blood drops being collected on a special card. The screening aims to detect the presence of the sickle cell gene.

Similarly, the disease can be detected during pregnancy. Expecting mothers are offered blood tests, ideally performed before reaching 10 weeks of pregnancy. In the case of a positive result, further testing is required to confirm the diagnosis. Amniocentesis and chorionic villus sampling are the available diagnostic tests in which a sample of amniotic fluid and placental cells are collected, respectively, for analysis.

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How is sickle cell anaemia managed? 💊

The only treatment available to cure sickle cell anaemia is a bone marrow transplant.

Therefore, management options are aimed at improving patients' quality of life by alleviating symptoms and preventing complications.

• Hydroxycarbamide helps maintain the normal shape of red blood cells by increasing the levels of haemoglobin F. In turn, this reduces the frequency and severity of sickle cell crises.

• Crizanlizumab reduces the likelihood of vaso-occlusive crises by preventing the clumping of blood cells. It is administered by intravenous infusion.

• Paracetamol and ibuprofen are recommended for mild pain management, while opioid painkillers such as morphine are typically prescribed for severe pain.

• Individuals with sickle cell anaemia should drink plenty of fluids and keep themselves warm.

• Regular blood transfusions are used to replace sickle cells with healthy red blood cells.

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For more information, please visit:

• https://www.sparksicklecellchange.com/sickle-cell-genetics/inheritance - provides a tool to determine the probability of sickle cell inheritance.

• https://www.sicklecellsociety.org/ - the charity in the United Kingdom that supports people affected by sickle cell disease.

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Edited by: Olivia Laughton | Content Editor | BSc Microbiology, University of Leeds

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