Sickle Cell Disease

What is sickle cell disease?

Sickle cell disease affects a protein in one of the types of cells circulating in the blood: red blood cells. [1]  Proteins behave like messengers, travelling around the body to carry out tasks needed to support the body. Red blood cells are full of proteins called haemoglobin (HbA), which carry oxygen around the body. [2]  

Red blood cells are usually shaped like discs and are flexible, allowing them to easily squeeze through small blood vessels. [3]  In people with sickle cell disease, instead of normal HbA, sickle haemoglobin (HbS) is made. HbS proteins can assemble into stiff rods that distort the red blood cells into a sickle shape (curved or half-moon shaped). [3, 4] Because sickled red blood cells are rigid and sticky [5], they can also trap other blood cells, such as white blood cells and platelets, and form clusters in blood vessels. [6] This causes blockages in the blood vessels that prevent blood and oxygen from reaching parts of the body. The blockages can also lead to pain episodes/crises, which are also known as vaso-occlusive episodes (VOE) or vaso-occlusive crises (VOC). Over time, repeated blockages can damage organs and other parts of the body. [1]

Where in the world are people affected with sickle cell disease? 

Sickle cell disease is an inherited blood disease that affects over 20 million people across the world. [4, 7] The ‘carrier’ state for sickle cell disease (‘sickle cell trait’) generally has no symptoms and is protective against malaria. [1, 8] As a result, sickle cell disease is most common in regions affected by malaria, such as parts of Africa, the Middle East, India, and the Mediterranean region. [1] However, immigration from these regions to other parts of the world has led to distribution of sickle cell disease globally. [1] The map below shows the number of babies born with sickle cell anaemia (the most common form of sickle cell disease) in different parts of the world. [1] Researchers estimate that roughly 300,000–400,000 babies worldwide are born with sickle cell disease every year. [4] 

How is sickle cell disease inherited?

Genes contain DNA, which tells the body how to make different proteins. People inherit genes from both their birth mother and birth father: each gene has two copies – one from each birth parent. [9] Eye colour and hair colour are examples of visible traits that are inherited genetically (through genes). 

Genes also determine what type of haemoglobin proteins are made. To be born with sickle cell disease, a child has to inherit at least one copy of the gene for HbS and also have a change in the other copy of their haemoglobin gene, rather than a normal HbA gene. People with sickle cell disease inherit either two copies of the HbS gene or one copy of the HbS gene plus another variation in the haemoglobin gene (for example, a variation called beta (β)-thalassemia [Hbβ+/Hbβ0] or haemoglobin C [HbC]). [10]

Sickle cell trait is a ‘silent’ carrier state, caused by inheriting a single gene for HbS. Sickle cell trait does not typically cause any symptoms but people with sickle cell trait have a chance of passing on their HbS gene to each child they have. [11]

What are the symptoms and complications of sickle cell disease?

Sickle cell disease can affect all parts of the body. [4]

The most common symptoms of sickle cell disease are pain crises, which happen when sickled red blood cells cause blockages in blood vessels. [4] The crises can be unpredictable and extremely painful [12, 13] and are the most common reason for emergency treatment and hospitalisation in people with sickle cell disease. [1, 4]

In addition to pain crises, blockages in blood vessels can have other effects throughout the body. These range from acute chest syndrome, to splenic sequestration (sickled red blood cells stuck in the spleen), priapism (prolonged, painful erections) and an increased risk of stroke for both adults and children. [4, 14]  

Additionally, over time, repeated blockages and pain crises also cause long-term (chronic) pain and damage to vital organs and tissues. [4] These are illustrated in the diagram below. [4, 5, 10, 15]  

How is sickle cell disease treated?

Most of the current treatments for sickle cell disease aim to reduce painful crises, but not all are available in every country: [4]

• Hydroxyurea (hi-droxy-you-ree-ah) is a tablet taken by mouth. It decreases the frequency of pain crises by reducing the concentration of sickle haemoglobin in red blood cells by increasing the production of another type of haemoglobin, foetal haemoglobin (HbF) [16]
• L-glutamine (el-gloot-a-meen) is a powder taken by mouth that has antioxidant activity. It decreases the frequency of pain crises, possibly by reducing damage to sickled red blood cells [17]
• Crizanlizumab (crizz-an-lizz-oo-mab) is a medication given by an infusion into the vein. It reduces the frequency of pain crises by blocking the activity of a sticky (adhesion) factor in blood vessels [18]
• Voxelotor (vox-el-oh-tor) is a tablet taken by mouth. It binds to sickle haemoglobin and is thought to prevent it from assembling into rods, reducing the formation of sickled red blood cells. [19]

Currently a stem cell transplant is the only way of curing sickle cell disease. It is not performed very often, as suitable donors can be hard to identify, but may be offered to some patients who would benefit from the procedure. [4]

People with sickle cell disease are also given preventative treatments to try and reduce the risk of certain complications. 

• In children, penicillin (an antibiotic) is given to help protect against bacterial infections [4]
• Vaccines are given from early childhood through to adulthood to help protect against bacterial infections [4]
• Blood transfusions (infusion of blood from a donor) may be used to help manage patients with certain complications of sickle cell disease. Red blood cells from the transfusions help to carry more oxygen around the body and reduce the proportion of HbS in the blood [20]

Some people with sickle cell disease may use additional approaches to manage the pain associated with their condition, such as staying hydrated, distraction techniques or acupuncture. [21] However, what works for some may not work for others: each person should work with their doctor to find the best way to manage their sickle cell disease. 

Researchers are continuing to look for more effective treatment options for patients with sickle cell disease in ongoing clinical trials.