Sickle Cell Disease

Sickle cell disease is a group of inherited blood disorders that causes red blood cells to become rigid and crescent-shaped, blocking blood flow and leading to severe pain, infections, and organ damage throughout the body.

Table of contents

• What is sickle cell disease?
• Causes and inheritance
• Types of sickle cell disease
• Symptoms and complications
• Diagnosis and screening
• Treatment options
• Living with sickle cell disease
• Outlook and life expectancy

What is sickle cell disease?

Sickle cell disease is a group of inherited blood disorders that affect red blood cells, the cells responsible for carrying oxygen throughout your body^[1]. In people with this condition, red blood cells become abnormally shaped like a crescent moon or a farm tool called a sickle, instead of their normal round, flexible shape^[2].

These sickle-shaped cells are rigid and sticky, which causes two major problems. First, they break apart and die much more quickly than normal red blood cells, typically lasting only 10 to 20 days compared to the normal 120 days^[3]. This creates a constant shortage of red blood cells, a condition called anemia (when your blood doesn’t have enough healthy red blood cells to carry oxygen). Second, the abnormal cells get stuck in small blood vessels and block blood flow, preventing oxygen from reaching your tissues and organs^[1].

Approximately 7.74 million people were living with sickle cell disease globally in 2021, with about 515,000 new births affected by the condition^[8]. In the United States, the disease affects between 70,000 and 100,000 people^[4]. The condition is most common among people with African or Caribbean family backgrounds, but it also affects individuals with southern European, Middle Eastern, or Asian Indian ancestry^[5].

sickle cell anemia, drepanocytosis

Causes and inheritance

Sickle cell disease is caused by a genetic mutation (a change in a gene) in the HBB gene, which provides instructions for making hemoglobin, the protein in red blood cells that carries oxygen^[8]. This mutation leads to the production of an abnormal type of hemoglobin called hemoglobin S^[2].

The condition is inherited, meaning it is passed down from parents to their children through genes. For a child to have sickle cell disease, they must inherit two copies of the gene that causes the condition, one from each parent^[2]. If both parents have the gene, there is a 1 in 4 chance that each child they have will be born with sickle cell disease^[5].

If a person inherits only one copy of the hemoglobin S gene from one parent and a normal gene from the other parent, they have what is called sickle cell trait^[2]. People with sickle cell trait typically do not have symptoms of the disease and live normal lives. However, they can pass the abnormal gene to their children. About 1 in 12 people of African descent carries a sickle cell gene^[4].

Types of sickle cell disease

There are several types of sickle cell disease, depending on which genes a person inherits from their parents. The specific type affects how severe the symptoms may be^[2].

Hemoglobin SS (HbSS), also called sickle cell anemia, is the most common and most severe form of the disease. People with HbSS inherit two hemoglobin S genes, one from each parent^[2].

Hemoglobin SC (HbSC) occurs when a person inherits one hemoglobin S gene from one parent and a gene for another abnormal type of hemoglobin called hemoglobin C from the other parent. This form usually causes mild to moderate symptoms^[2].

Sickle cell beta thalassemia (HbS/beta-thal) happens when a person inherits one hemoglobin S gene and one gene for beta thalassemia, another type of blood disorder. There are two types: HbS beta0-thalassemia, which usually causes severe symptoms, and HbS beta+-thalassemia, which tends to be milder^[2].

There are also rare forms of sickle cell disease, such as HbSD, HbSE, and HbSO. These occur when a person inherits one hemoglobin S gene and another gene that makes a different type of abnormal hemoglobin. The severity of these rare types varies^[2].

Symptoms and complications

Symptoms of sickle cell disease usually begin to appear around 5 to 6 months of age^[3]. The signs vary greatly from person to person and may change over time. Some people have mild symptoms and lead relatively normal lives most of the time, while others experience severe and frequent complications^[5].

Common symptoms include anemia, which causes extreme fatigue, weakness, and paleness. Babies and young children with anemia may seem unusually fussy and irritable^[6]. Many people also develop yellowing of the skin and whites of the eyes, called jaundice, which happens when the sickled cells break down quickly and release a substance called bilirubin^[3].

One of the first symptoms in babies is painful swelling of the hands and feet. This occurs when sickled cells get stuck in blood vessels and prevent blood from flowing to the hands and feet^[3].

Episodes of severe pain, called pain crises or sickle cell crises, are a major symptom of the disease. These happen when sickle-shaped cells block blood flow through small blood vessels to the chest, abdomen, bones, and joints^[1]. The pain can vary in intensity and may last for a few hours to several days. Some people have only a few pain crises a year, while others have a dozen or more^[3]. A severe pain crisis may require hospitalization and treatment with strong pain medications^[3].

Sickle cell disease can lead to serious and life-threatening complications. People with the condition have an increased risk of infections because the disease affects the spleen, an organ that helps fight infections^[5]. Young children are particularly vulnerable to bacterial infections, which is why any fever in someone with sickle cell disease must be taken very seriously^[12].

Acute chest syndrome is a dangerous lung complication that can lower oxygen levels in the blood and cause severe chest pain and breathing problems^[7]. This condition can be deadly, especially in children.

Stroke is another serious complication, particularly in children. It occurs when sickled cells block blood flow to the brain^[4]. Other complications include kidney damage, kidney failure, vision problems, leg ulcers that don’t heal, priapism (painful, prolonged erection in males), delayed growth in children, and organ damage affecting the heart, liver, and other organs^[3][8].

Diagnosis and screening

In the United States, sickle cell disease is often detected at birth through routine newborn screening^[2]. All newborns in the United States are now tested for the disease as part of standard newborn blood screening tests, sometimes called the heel prick test^[4].

A blood test can check for the abnormal form of hemoglobin that causes sickle cell disease^[11]. If the screening test suggests sickle cell disease, additional blood tests are done to confirm the diagnosis.

Sickle cell disease can also be diagnosed before birth. Pregnant women can have testing during pregnancy by sampling amniotic fluid (the fluid surrounding the baby) or tissue from the placenta^[4]. If you or your partner has sickle cell disease or carries the sickle cell gene, you can speak with a genetic counselor before pregnancy to discuss your options^[4].

Blood tests can be performed at any age to check for sickle cell disease or to see if someone carries the gene that causes it^[5].

Treatment options

While there is no single standard treatment that cures most people with sickle cell disease, many treatments are available to help manage symptoms, prevent complications, and improve quality of life^[4]. Treatment is lifelong and is best provided by a team of healthcare professionals at a specialist sickle cell center^[13].

Several medicines have been approved by the U.S. Food and Drug Administration (FDA) to treat sickle cell disease. Hydroxyurea was the first medicine approved in 1998 and remains a first-line treatment. It reduces the frequency of pain crises and can reduce the need for blood transfusions and hospitalizations^[10][11]. The medicine is recommended for patients as young as nine months old.

Other approved medicines include L-glutamine, which was approved in 2017 for patients five years old and above, and crizanlizumab, approved in 2019 for patients 16 years and older. These medicines also help reduce the frequency of pain crises^[12].

In September 2024, a medicine called voxelotor (Oxbryta) was withdrawn from the market. The manufacturer stated that the benefits of using this medicine did not outweigh the risks^[1][10].

In December 2023, the FDA approved two new gene therapies that are considered transformative treatments for sickle cell disease. One treatment adds a modified gene into the body, and the other makes a change to a gene that is already in the body^[10].

Blood transfusions are another important treatment. They can help treat and prevent complications such as stroke by increasing the number of normal red blood cells^[12]. Some people may need only a single transfusion, while others require regular transfusions.

Stem cell transplant or bone marrow transplant is currently the only widely available cure for sickle cell disease. However, it is not done very often because of the significant risks involved^[5][13]. The procedure works by replacing the stem cells of the person with sickle cell disease with stem cells from a healthy donor. Transplants are generally only considered in children with severe symptoms when a closely matched donor, such as a family member, is available^[4].

Treatment for pain crises often includes pain medications, both over-the-counter medicines like paracetamol or ibuprofen and stronger prescription painkillers^[13]. Other methods that may help manage pain include heating pads, warm baths, massage, and physical therapy^[12].

To prevent infections, people with sickle cell disease typically take daily antibiotics, usually penicillin, often for the rest of their lives^[13]. They should also receive all routine vaccinations, as well as additional ones like the annual flu vaccine and vaccines against pneumonia and meningitis^[17].

Living with sickle cell disease

People with sickle cell disease can live full, active lives and participate in most of the same activities as other people^[17]. However, it is important to work closely with your healthcare team to manage the condition and prevent complications.

Regular follow-up care is essential. Most people with sickle cell disease should see their healthcare provider every 3 to 12 months, depending on their age and the type of disease they have^[17]. Babies from birth to 1 year should be seen every 2 to 3 months.

Staying hydrated is very important. People with sickle cell disease should drink 8 to 10 glasses of water every day, and even more if exercising or in hot weather^[19]. Dehydration increases the risk of a pain crisis.

Maintaining a healthy lifestyle helps manage the condition. This includes eating plenty of fruits, vegetables, whole grains, and protein, getting enough sleep, and engaging in regular but moderate physical activity^[17]. It is important not to overdo physical activity and to rest when tired.

Certain situations can trigger pain crises and should be avoided when possible. These include extreme heat or cold, sudden temperature changes (such as swimming in cold water), high altitudes where oxygen levels are lower, very strenuous exercise that causes serious breathlessness, dehydration, alcohol, and smoking^[18]. Stress can also trigger crises, so learning relaxation techniques may be helpful.

Taking all prescribed medicines as directed is crucial. This includes daily preventive medicines as well as any treatments prescribed for managing symptoms^[17].

It is important to know when to seek immediate medical care. Contact your healthcare provider or go to the emergency department right away if you develop a high fever (over 38°C), severe pain that doesn’t respond to home treatment, severe vomiting or diarrhea, severe headache or stiff neck, breathing difficulties, very pale skin or lips, sudden swelling in the abdomen, painful erection lasting more than 2 hours, confusion or drowsiness, fits (seizures), weakness on one or both sides of the body, or sudden vision changes^[18].

Living with sickle cell disease can be stressful and may cause feelings of sadness or depression. Speaking with a counselor or participating in a support group can be helpful^[22]. Family and friends can provide important emotional support.

Women with sickle cell disease can have healthy pregnancies, but it is important to speak with your healthcare team before trying to get pregnant. Some medicines used to treat sickle cell disease can harm an unborn baby and may need to be stopped before pregnancy^[18]. Pregnancy in women with sickle cell disease carries increased risks, including anemia, pain crises, miscarriage, and other complications, so extra monitoring and treatment may be needed.

Outlook and life expectancy

Sickle cell disease varies greatly between individuals, from mild to serious. Most people with the condition lead happy and normal lives^[5]. Mild sickle cell disease may have no impact on a person’s day-to-day life, while more severe forms can significantly affect daily activities.

With proper treatment and care, many people with sickle cell disease now live into their 50s or beyond^[16]. In the past, babies born with this condition rarely lived to be adults, but thanks to early detection through newborn screening and improved treatments, outcomes have improved considerably.

The outlook depends on several factors, including the specific type of sickle cell disease, how well it is managed, the availability of good medical care, and whether serious complications develop. Life expectancy tends to be shorter than normal, but this varies depending on the exact type of disease and the quality of care received^[5].

In 2021, sickle cell disease caused 81,100 deaths in children under 5 years old globally, making it the 12th leading cause of death in this age group. However, traditional mortality recording significantly underestimates the true impact of the disease^[8].

Regular medical care, adherence to treatment plans, and healthy lifestyle choices can help reduce symptoms, lower the risk of complications, and improve quality of life for people with sickle cell disease^[1].