Sickle cell disease

Sickle cell disease, also called sickle cell, is a group of inherited blood disorders that affect the oxygen-carrying protein in red blood cells. This causes the cells to change shape into a sickle-like form, which can block small blood vessels and cause pain and other health problems. These issues usually start around 5 to 6 months of age and can include pain crises, swelling, infections, dizziness, and even stroke.

People inherit sickle cell disease from their parents, each providing a copy of an abnormal gene. Without treatment, it used to be life-threatening, but with good healthcare, many people now live into their 60s. Care includes preventing infections, staying hydrated, taking certain vitamins, and using pain medicine or blood transfusions. New gene therapies approved in 2023 offer hope for even better treatment.

About 7.7 million people worldwide have sickle cell disease, mostly in sub-Saharan Africa, but it also occurs in parts of India, Southern Europe, West Asia, North Africa, and among people of African origin living elsewhere. The condition was first described in 1910 and was found to protect carriers from malaria, which helps explain why it is common in areas where malaria is a problem.

Signs and symptoms

Signs of sickle cell disease often appear when children are very young. How severe these signs are can differ a lot from one child to another. This disease can cause both sudden and ongoing health problems.

One of the first signs can be pain and swelling in a child’s hands and feet. Other early signs might include looking pale, feeling very tired, or having a yellow tint to the skin. As children get older, painful episodes in different parts of the body become more common.

The disease can cause severe pain when tiny blood vessels get blocked, leading to problems in parts of the body like the chest or legs. This pain can be managed with medicine, but sometimes needs special care in a hospital. Other serious problems can include the spleen swelling suddenly, which needs quick medical help, or lung issues that can be very serious. There are also risks of infections, problems with the brain’s blood flow, and damage to other organs like the kidneys and bones.

Genetics

See also: Introduction to genetics

See also: Price equation examples § Evolution of sickle cell disease

Haemoglobin is a special protein in red blood cells that carries oxygen from the lungs to the rest of the body. Normally, there are different types of haemoglobin at different ages, but one important type in adults is called haemoglobin A.

In sickle cell disease, a small change happens in the genes that tell the body how to make haemoglobin. This change creates a different kind called haemoglobin S. When someone has two copies of this changed gene, their red blood cells can change shape and become stiff, which can cause health problems. If someone has only one changed gene, they usually don’t have many symptoms but can pass the gene to their children.

Sickle cell disease is more common in places where malaria is common because having one changed gene can help protect a person from severe malaria. This is why the disease is still found in areas like Africa, the Mediterranean, India, and the Middle East.

Pathophysiology

When there is less oxygen, special proteins in red blood cells change shape and make the cells hard and pointy. These hard cells can’t move easily through tiny blood vessels, which can block blood flow and hurt body parts. Over time, these cells get damaged and can’t return to their normal shape.

Red blood cells in healthy people are soft and flexible, but in sickle cell disease, they become stiff and break apart too quickly. This makes the body lose red blood cells faster than it can make new ones, leading to tiredness and weakness. The breakdown of these cells also releases substances that can cause swelling and more problems in the body.

Diagnosis

Checking for sickle cell disease can start before a baby is born. During pregnancy, doctors can test a small sample of fluid or blood to look for the disease. After the baby is born, a simple test called a heel prick is often used to check for sickle cell disease and other conditions.

When doctors think someone might have sickle cell disease, they can use different tests to find out. Some tests look at the shape of the blood cells under a microscope. Others use special techniques to see the types of haemoglobin in the blood. These tests help doctors understand if someone has the disease and what kind it might be.

Genetic counselling

Genetic counselling is a way to help families understand how some health problems can be passed down through families. It can give people information about their chances of having a child with a certain condition and what they can do about it.

People who might pass on sickle cell disease or have a child with it can talk to special helpers called genetic counsellors. These helpers explain the good and bad parts of testing for the disease and what the results might mean. It's best to get this help before having a baby. Some choices families can discuss include adopting a child, using healthy donor eggs or sperm, or using a special lab technique called IVF together with a test to check embryos for the disease before they are implanted.

Treatment

Further information: Pain management in children

Several steps can help prevent painful episodes for people with sickle cell disease. Staying well hydrated, avoiding too much physical activity, and keeping stress low are important. Since low oxygen levels can cause problems, it’s best to avoid high places like tall mountains or flying in planes without pressure. Avoiding alcohol and smoking also helps, as these can cause problems.

Children with sickle cell disease are often given a special medicine called penicillin for the first few years to help prevent infections. They should also get all recommended vaccines to stay healthy. A medicine called hydroxyurea can help reduce painful episodes and has been used for many years. Another medicine, Voxelotor, was approved but later stopped because of safety concerns.

Blood transfusion

Main article: Transfusion therapy (Sickle-cell disease)

A simple transfusion adds healthy blood from a donor to help with low blood levels and reduce pain. It can be used before surgery or pregnancy, and to prevent long-term problems.

In an exchange transfusion, some of the patient’s blood is removed and replaced with healthy blood. This is used in serious cases or during pregnancy.

Stroke prevention

A special ultrasound test can find children at risk of stroke. Regular blood transfusions can help prevent strokes in these children.

Vaso-occlusive crisis

People with sickle cell disease can have very painful episodes called vaso-occlusive crises. Pain can occur anywhere in the body and varies from mild to severe. Home care includes rest, hydration, and pain medicine. Stronger medicines may be needed for severe pain.

Acute chest syndrome

This condition affects the lungs and needs treatment with pain medicine, antibiotics to prevent infection, and extra oxygen. Blood transfusions might be needed in severe cases.

Treating avascular necrosis

Treatment for bone damage includes resting the joint, physical therapy, pain medicine, surgery, or bone grafting.

Psychological therapy

Therapies like learning more about the disease, thinking strategies, and behavior changes can help, but more research is needed to see how well they work.

Stem cell treatments

Haematopoietic stem cells (HSC) are cells in the bone marrow that can become all types of blood cells, like red blood cells, white blood cells, and platelets. There are two ways doctors can use these cells to help treat sickle cell disease. Since 1991, some patients have had bone marrow transplants from healthy donors who are a match. This is a big operation with risks. Recently, doctors have started using a special tool called CRISPR gene editing to change the patient’s own HSC cells. This can lower or stop the problem that causes sickle cell disease.

All of these treatments need a step called myeloablation, where the patient’s bone marrow is cleared out using high doses of chemotherapy. This can make the patient feel very sick and tired. After the new cells are put in, the patient stays in the hospital for a long time while the new cells settle into the bone marrow and start making healthy red blood cells.

Gene therapy

Gene therapy was first tried in 2014 on one patient, and then more patients were treated in later tests. In 2023, two new treatments called exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) were approved for sickle cell disease. In October 2024, Kendric Cromer became the first person in the US to get this treatment and left Children's National Hospital. Starting in 2025, Casgevy will be offered to patients in England through the National Health Service.

Both Casgevy and Lyfgenia work by taking the patient’s HSC cells out, changing their DNA in the lab with CRISPR, and then putting them back in after the bone marrow is cleared out. Casgevy changes a gene called BCL11A, which helps the body make more of a special kind of haemoglobin that does not get sickled. Lyfgenia adds a new gene that works together with the sickled haemoglobin to reduce sickling.

Hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) replaces the sick cells in a person with sickle cell disease with healthy cells from a well-matched donor. It is very important to find a donor who matches well. Possible donors can include umbilical cord blood, human leukocyte antigen matched family members, or unrelated donors who are a match. There are some risks with HSCT, like problems with the new cells not working right or other side effects from the transplant.

Prognosis

Sickle cell disease is most common in sub-saharan Africa. In places without good healthcare, many children with the disease may not live past age five.

However, in countries like the United States and the UK, people with this condition can live much longer. In the United States between 2010 and 2020, the average lifespan was about 43 years, and in the UK it was around 67 years.

Epidemiology

The HbS gene can be found in people from all backgrounds, but sickle cell disease is most common in tropical areas, especially in sub-Saharan Africa, parts of India, and the Middle East. About 80% of cases happen in sub-Saharan Africa. As people move from these areas to places like Europe, the disease has become more common there too. In 2015, it caused around 114,800 deaths.

Sickle cell disease is more common where malaria is or was common because carrying one copy of the gene can help protect against severe malaria. This condition is passed down through families in a special way, where both parents carry one copy of the changed gene but usually don’t show symptoms themselves.

Three-quarters of cases occur in Africa. In Nigeria, about 2% of newborns have sickle cell anaemia, meaning around 150,000 children are born with it each year. In France, sickle cell disease is now the most common genetic condition, affecting about one in 2,415 newborns. Since 2000, all newborns considered “at-risk” are screened for the disease, and since August 2024, all newborns in France are screened.

In the United Kingdom, between 12,000 and 15,000 people have sickle cell disease, with about 250,000 carriers in England. All newborns are screened, and pregnant couples and blood donors are also tested.

In Saudi Arabia, about 4.2% of people carry the sickle cell trait, and 0.26% have the disease. In Bahrain, 2% of newborns have the disease, and screening programs have been in place since the 1990s.

Sickle cell disease is also common in some parts of India and Nepal, and in the Caribbean Islands, like Jamaica, where 10% of the population carries the gene.

History

The first modern description of sickle cell disease may have been in 1846, when doctors examined a runaway slave after his death. In 1910, a doctor named Ernest E. Irons noticed unusual, sickle-shaped cells in the blood of a young dental student named Walter Clement Noel. Noel had anemia but continued his studies and returned to Grenada, where he later died from pneumonia.

More research followed, and by the 1930s, doctors began to understand more about the disease. In the 1970s and 1980s, new treatments were developed, and in the 1990s, a medicine called hydroxycarbamide was created to help manage the condition.

Society and culture

United States

In the US, people with sickle cell disease sometimes face unfair treatment that makes it harder for them to get the care they need. This is partly because most people with this condition are Black, and there has been racism affecting their treatment. In 1970, the Black Panther Party opened many free clinics across the U.S. where people could get free tests for sickle cell disease. Thousands of African-Americans were tested at these clinics during the 1970s.

In September 2017, the U.S. Social Security Administration made a new policy to help explain how they decide if someone with sickle cell disease qualifies for disability benefits.

Uganda

Uganda has one of the highest numbers of people with sickle cell disease in the world. Many people there do not understand the disease well, which leads to unfair treatment of those who have it. Some believe the disease is a punishment from God or caused by witchcraft, even though it is actually genetic. This misunderstanding causes bullying and rejection for people with the disease.

There is not much updated information about sickle cell disease in Uganda because the government does not fund much research. About 20% of the population carries the gene for the disease, and around 25,000 children are born with it each year. Many of these children do not live past the age of five. The only clinic for sickle cell disease in Uganda sees about 200 patients each day.

United Kingdom

The National Health Service in the UK offers several treatments for sickle cell disease, including pain management, antibiotics to prevent infections, and blood transfusions when needed. There are also newer treatments like Voxelotor and a gene therapy called Casgevy. Several hospitals across England specialize in treating sickle cell disease and other blood disorders.

Media and arts representation of sickle cell disease

Movies, television shows, and art have helped teach people about sickle cell disease and support those who live with it. Artists and actors have used their work to raise awareness and fight for better care. Shows like ER, Supacell, Lady in the Lake, and The Pitt, as well as movies like A Warm December, Mortal Inheritance, and Transformers: Rise of the Beasts, have included characters with sickle cell disease to help others understand the condition.