What is Sickle Cell?

Sickle cell disease affects up to 15,000 people in the UK, growing in number year on year. Currently, 1 in 79 babies in the UK are carriers of the sickle cell trait, with 300 babies born with the condition each year, making it the fastest growing genetic condition in the UK.

What is sickle cell disease?

Sickle cell disease, known as SCD, is a disease that affects the haemoglobin of red blood cells. Inherited from a child’s parents, sickle cell disease can only be transmitted genetically, and is present and detectable from birth. Usually, red blood cells, which are responsible for carrying haemoglobin throughout the body, are shaped in a 3D disc form. In a sickle cell patient, due to defective haemoglobin, red blood cells are sickled, shaped in a crescent form, decreasing the surface area of the blood cell, which reduces how much oxygen the blood cell can carry. Thus, the distribution of oxygen around the body is decreased. Organs and tissue may not receive enough oxygen, leading to organ damage over time. As the blood cells are crescent shaped, they are not able to flow past each other as easily. This leads to blood flow becoming blocked, resulting in what is known as a ‘sickle cell crisis’, a severe episode of pain, which is typically only relieved by strong painkillers.

What are the types of sickle cell disease?

There are several forms of sickle cell disease: Sickle Cell Anaemia (SS), Sickle Haemoglobin-C Disease (SC), Sickle Beta Plus Thalassemia and Sickle Beta Zero Thalassemia.

Sickle Cell Anaemia (SS)

Referred to as HbSS, people who have sickle cell tend to have a more severe form of the condition. It is the most common type of sickle cell. It occurs when you inherit a copy of the abnormal red blood protein, haemoglobin S, from both parents.

Sickle Haemoglobin-C Disease (SC)

HbSC is the second most common form of the sickle cell condition. Someone with HbSC inherits the HbS gene from one parent, and another abnormal red blood protein, HbC, from the other. This form of sickle cell disease is often milder than HbSS, with painful symptoms often being experienced until after childhood. This condition should not be confused with Haemoglobin C Disease.

Sickle Beta Plus Thalassemia

Sickle Beta Plus Thalassemia is a mild type of sickle cell condition, where one has some normal haemoglobin, which allows the blood cells to be shaped like discs and glide past each other, and some abnormal haemoglobin, resulting in sickle cells. People with this form of the condition tend to have fewer red blood cells, or cells that are smaller than they should be.

Sickle Beta Zero Thalassemia

Sickle Beta Zero Thalassemia is different to Sickle Beta Plus, HbSC and HbSS, as there is no normal haemoglobin present. Unlike HbSS and HbSC, which is caused by the presence of abnormal haemoglobins S or C, Sickle Beta Zero Thalassemia is caused by a defect in the beta-globin gene. People with this condition will have mild symptoms in comparison to HbSC and HbSS.

What is Sickle Cell Trait?

Sickle Cell Trait (SCT) simply refers to the gene that can cause sickle cell disease. Someone with SCT has inherited the gene from one or both of their parents. Someone with SCT does not have sickle cell disease and can live a completely normal life.

In very rare instances, people with SCT have been known to have symptoms similar to someone with SCD, reporting pain crises. These pain crises are sometimes triggered by atmospheric pressured environments, such as whilst scuba diving, and low levels of oxygen when at elevated levels such as whilst flying or ascending mountains. Dehydration can be a factor too.

It is unclear as to why most people with SCT do not have symptoms, yet some experience similar symptoms to someone with the disease.

What causes sickle cell disease?

Sickle cell disease is inherited from parents just as other genetic traits, such as eye colour, hair colour and blood type. A child inherits the type of haemoglobin they produce from their parents. Inheritance works in the following way:

• One parent with Sickle Cell Anaemia + one parent without Sickle Cell Anaemia or the Sickle Cell Trait = each child will inherit the sickle cell trait.
• One parent with Sickle Cell Anaemia + one parent with the Sickle Cell Trait = a 50% chance of each child having Sickle Cell Disease, and a 50% chance of each child developing the trait. They will definitely inherit one.
• Both parents with Sickle Cell Trait = a 25% chance of each child having Sickle Cell Anaemia, and a 50% chance they will inherit the trait.
• One parent with Sickle Cell Trait + one parent without the trait = a 50% chance of each child inheriting the trait.

What causes crises?

People with sickle cell disease are prone to painful episodes of pain, known as crises. This is the most common symptom of sickle cell disease. A pain crisis occurs when the sickle-shaped cells gather and block the flow of blood in blood vessels. This can cause intense pain, ranging from a dull pain to sharp, stabbing pains, and can lead to severe complications, such as organ damage, blood clots and stroke.

There are four main types of crisis:

Aplastic

An aplastic crisis occurs when red blood cell production is halted, or slowed. This means that the body is not producing enough new red blood cells. The red blood cells in someone with SCD have a shorter lifespan than usual, so if red blood cells are not constantly being produced, the level of haemoglobin drops quickly, causing severe anaemia.

Acute sequestration

Acute sequestration is a crisis that usually affects younger children, impacting the spleen. The spleen, which controls the level and quality of blood cells in the body, usually receives around 3-5% of the body’s blood per minute. Blood can become trapped in the spleen, being filled with an excessive amount of blood, which causes the rest of the body to lack haemoglobin to a dangerous level. The body can go into hypovolemic shock, due to the lack of blood circulating to the rest of the organs. In the most severe cases, death can occur within hours. People with SCD types HbSC and HbSβ+thalassemia are less prone to splenic infarction but may continue to have an enlarged spleen throughout adulthood. If the infarction is recurring, a splenectomy is the usual course of action, due to its life-threatening nature.

Hyperhaemolytic

A hyperhaemolytic crisis is a crisis that usually occurs post-blood transfusion when the original red blood cells and the donor red blood cells undergo haemolysis, the destruction of red blood cells. This can be caused by alloimmunisation, which is when the individual’s antibodies recognise foreign surface antigens on the transfused red blood cells, destroying the blood cells. This leads to severe anaemia.

Vaso-occlusive

A vaso-occlusive crisis occurs when sickled red blood cells block the flow of blood, causing the surrounding tissue to lack oxygen and die. The pain arises from the body’s inflammatory response to counteract the problem. VOCs are thought to be triggered by cold temperatures, dehydration, infections, stress, poor sleep and low levels of oxygen. This is the most common cause of hospitalisation of people with SCD. These crises can last anywhere between 2 and 7 days. In this case, the main course of treatment is pain management, through opioids, and boosting oxygen levels. Blood transfusions may be used too.

What are the symptoms of sickle cell disease?

Different types of sickle cell disease have different symptoms.

Most commonly found are the following symptoms:

• Anaemia. Due to red blood cells having a shorter life span, the body can be left without enough red blood cells, causing a shortage of oxygen in the body. The main side effect of anaemia is fatigue.
• Pain crises. As described above, episodes of extreme pain are commonplace in some types of SCD, due to the flow of blood in blood vessels being blocked by the sickled red blood cells.
• Problems with eyesight. Sickled cells can block the blood vessels that supply blood to the retina, damaging it and causing vision problems. Other people report seeing ‘floaters’. In rare cases, sudden loss of vision can occur.
• Higher risk of infection. People with sickle cell may experience spleen damage, which can increase the propensity to infection.
• Swollen hands and feet. This is due to the lack of blood circulating in the extremities.
• Delayed puberty. Due to a lack of normal oxygen levels in some children with SCD, cells may develop more slowly.

Other symptoms may include:

• Chronic pain in the bones and joints.
• Priapism – these are erections that can last for hours, and be very painful.
• Urinary problems.
• Leg ulcers.
• Abdominal pain, caused by gallstones.
• Yellowing of the skin and eyes.

What are the complications of sickle cell?

There are serious complications associated with sickle cell disease, which include:

Stroke

People with SCD are more likely to suffer from stroke, or transient ischaemic attacks (mini-strokes), due to the flow of blood to the brain being blocked. Children with SCD are more likely to have a stroke and can be given regular ultrasounds to find out if they are at high risk.

Acute chest syndrome

Acute chest syndrome is a severe condition affecting the lungs, usually triggered by viral and bacterial infections, such as bacterial pneumonia. In sickle cell patients, acute chest syndrome is caused by vaso-occlusion in the blood vessels between the heart and the lungs. Treatment for this must be quick and hard-hitting, as acute chest syndrome is responsible for injury to the lungs, and low oxygen levels in the rest of the body, which can result in death.

Organ and tissue damage

As blood flows to the organs in sickle cell patients is reduced, particularly during crises, organs and tissue may be regularly starved of oxygen, causing the tissue to die. The spleen is usually the first organ affected, but a lack of fully oxygenated blood can damage the nerves, the kidneys, the liver and other organs. It can also cause osteonecrosis, or avascular necrosis (AVN), which is the death of the tissue bone, due to the loss of blood supply, usually affecting the hip or the shoulder joints. Eventually, AVN can lead to surgery, either repositioning the bone or replacing it completely.

Dactylitis

Dactylitis, sometimes called ‘hand-foot syndrome’, is the swelling of individual fingers and toes, rather than a hand or a joint. It causes extreme pain, due to the circulation of the blood being blocked.

Blood clots

People with SCD are more likely to experience blood clots in the legs, arms or pelvis, which can be fatal.

Pulmonary hypertension

People with SCD are more likely to have high blood pressure in their lungs. This can be dangerous, as it causes difficulty in breathing.

Sleep apnoea

People with SCD can develop lung problems that can lead to sleep-breathing disorders. Snoring and paused breathing during sleep can make it hard to get good sleep, leading to further complications.

Can sickle cell disease be prevented?

There is no known cure for sickle cell. Sickle cell is a genetic blood disorder, and there is no way to prevent it. Geneticists are researching potential ways to prevent SCD from being passed down.

Couples who are undergoing in vitro fertilisation (IVF) may be able to determine whether their child can be born without sickle cell. There is no reason for couples with sickle cell or sickle cell trait to experience fertility any differently to a healthy adult, but should they be using IVF to conceive, they can put their embryos through genetic testing, known as Preimplantation Genetic Testing for Monogenic Disorders (PGT-M). Through the method, embryos can be tested for chromosomal issues, and sickle cell. They can then choose if they wish to transfer the embryo or choose a healthier one.

Living with sickle cell disease

Living with sickle cell disease is different for every person. Some people, particularly those with the HbSS type, may experience symptoms from birth, and need regular hospitalisation, treatments and living support. Others may have pain crises very infrequently, whilst experiencing more gradual symptoms, such as osteonecrosis. They are likely to be able to live their lives relatively normally, with few hospitalisations.

Children will take antibiotics, penicillin, from a young age to prevent bacterial infections such as pneumococcal pneumonia. This is usually taken until the child is five years old. They will also take folic acid to replace the depletion of folate in the bloodstream, which helps to make new blood cells.

Living with sickle cell can be worrying for people with the condition, and the people around them. In recent years, there has been huge concern around the population of blood banks, with sickle cell patients needing regular blood transfusions. Sickle cell predominantly affects people of African ancestry, and blood from this demographic is needed for transfusions.

Furthermore, whilst research into treatments for sickle cell is advancing rapidly, many hospitals and health professionals are still not trained well enough to deal with the condition that affects Black African, Black Caribbean, South Asian and Mediterranean demographics. There are reported cases of sickle cell patients having to explain to doctors what sickle cell disease is whilst mid-crisis. This can lead to uncertainty about how effectively they will be treated.

Life expectancy may be a point of uncertainty for sickle cell patients and their loved ones. Before the 1970s, the average life expectancy of someone with sickle cell was 14 years old. Today, according to the Royal College of Pathologists, over 99% of people in the UK born with SCD survive until adulthood, with a mean life expectancy of 67. There are many people who live beyond this, and those with HbSC forms of the condition are even surpassing the national average life expectancy of 81. This can be attributed to many factors, including much more effective treatments and understanding of the condition and how to manage symptoms, as well as life expectancy increasing overall. People with SCD have the potential to live a full, happy and long life.

How is sickle cell disease diagnosed?

Sickle cell is diagnosed through a simple blood test, which checks the type of haemoglobin produced. This is a routine check for newborn babies. The heel prick test takes a tiny amount of blood from the baby’s heel. If for some reason the blood test is not clear, genetic testing can be done to help determine the type of sickle cell.

Sickle cell screening of the mother is usually carried out before 10 weeks of pregnancy, to determine whether the mother is a carrier of the trait.

How is sickle cell disease treated?

There is no cure for sickle cell, and treatment is aimed at the management of symptoms.

Medication

• During a pain crisis, SCD patients are typically given opioids such as codeine or morphine to ease the pain, whilst they wait for the pain to subside. This is not a long-term solution, as both medications are addictive, and the patient could become dependent.
• For people with frequent pain episodes, hydroxyurea may be offered by a consultant. The capsule, which is taken once daily, increases the production of haemoglobin F, enlarging the red blood cells and helping them to remain more round, and less likely to become sickled in shape. This reduces pain crises and is usually an effective treatment for people who have at least six crises per year or have had complications.
• A new medication, crizanlizumab, has been proven to be very effective in treating pain episodes. The injection is administered once monthly.
• As people with sickle cell are more at risk of infection, they may take penicillin or another antibiotic for the foreseeable future.
• Folic acid should be taken daily to improve sickle cell anaemia.

Self-help

A large part of treating SCD is through self-management, through the following methods:

• Drinking plenty of water. Dehydration can cause red blood cells to become clumped together and trigger a crisis.
• Keeping the body warm. Cold weather can cause poor blood circulation. This can be avoided by wearing warm clothes and using heat aids such as hot water bottles on painful areas.
• Some chronic pain can be managed through over-the-counter painkillers.

Blood transfusions

Blood transfusions may be necessary, and in some cases, this may be routine, occurring once or twice monthly. A blood transfusion helps to alleviate symptoms by replenishing the blood with healthy blood from a donor, temporarily increasing the number of healthy red blood cells and increasing the amount of oxygen in circulation. Whilst this treatment is often life-saving, it is a riskier process for sickle patients, as they may have a haemolytic reaction, causing haemoglobin levels to drop below pre-transfusion levels.

Bone marrow transplant

A bone marrow transplant is the only known cure for sickle cell disease. Since 1982, more than 500 children with SCD have been cured of the condition through this method. However, this procedure is rarely performed, due to the high risks associated, such as infection, graft-versus-host-disease, graft failure, infertility and nutritional problems. Whilst the chance of cure is high (90%) from a match-related donor, the risks make it preferable to treat the condition using other methods.

Who can support people with sickle cell disease?

• The Sickle Cell Society supports people affected by SCD to improve their quality of life, through community events, mentoring, information and campaigning for blood donation.
• Sickle Cell and Young Stroke Survivors support and educate people affected by sickle cell and stroke.
• Switch Up on Sickle Cell is a campaign by medical company Novartis that raises awareness around SCD. They provide support in managing SCD.