Sickle-cell disease (SCD)

Types of sickle cell disease

Types of sickle cell disease include:

• Hemoglobin? SS (HbSS). If you have HbSS, both copies of your HBB gene make hemoglobin? S. It’s the most common and severe form of SCD. It’s also called sickle cell anemia.
• Hemoglobin? SC (HbSC). If you have HbSC, one copy of your HBB gene makes hemoglobin? S and the other makes another abnormal type, hemoglobin C. HbSC usually causes mild to moderate symptoms.
• Sickle cell beta thalassemia (HbS/beta-thal). If you have HbS/beta-thal (also called hemoglobin? S beta thalassemia), you have one hemoglobin S gene. Your other HBB gene has a beta thalassemia variation that causes low levels of hemoglobin?.
• Rare forms of SCD. You might have one hemoglobin? S gene and one HBB gene that makes another type of abnormal hemoglobin? (like D, E or O). These combinations cause rare forms of SCD, including HbSD, HbSE and HbSO.

Both copies of your HBB gene have to have a variation for you to be diagnosed with SCD. If you have one hemoglobin? S gene and one normal HBB gene, you have sickle cell trait. People with sickle cell trait often don’t have any symptoms of sickle cell disease. But you can pass the abnormal gene on to your children.

Causes and risk factors

SCD is caused by a mutation in the HBB gene, which provides instructions for making haemoglobin. This mutation leads to the production of abnormal haemoglobin known as haemoglobin S. When a person inherits two copies of the haemoglobin S gene (one from each parent), they develop SCD. Individuals with one normal haemoglobin gene and one haemoglobin S gene have sickle-cell trait (SCT) and usually do not exhibit symptoms but can pass the gene to their offspring.

A genetic variation in the HBB gene causes sickle cell disease. The HBB gene has the instructions for making hemoglobin?, a part of your red blood cells that carries oxygen. Changes in this gene can make abnormal versions of hemoglobin, called hemoglobin S.

Normal red blood cells are donut-shaped. They’re flexible enough to move around the twists and turns of your blood vessels. This helps them bring oxygen to your organs and tissues. Red blood cells with hemoglobin? S can become C-shaped and stick together. They can get stuck as they travel through your body. They also don’t last as long as normal red blood cells. All of this means your tissues and organs may not get enough oxygen to work properly.

Symptoms

• Pain? episodes (crises): sudden, severe pain due to blocked blood flow. These episodes can last for hours to days and can be severe enough to require hospitalization.
• Anaemia: caused by the rapid breakdown of sickle-cells, leading to fatigue?, weakness?, and shortness of breath.
• Swelling?: particularly in the hands and feet, known as dactylitis, which is often the first symptom in babies.
• Frequent infections: due to spleen damage, which makes patients more susceptible to infections such as pneumonia.
• Delayed growth: in children and adolescents, due to chronic? anaemia and other complications.
• Vision problems: caused by blocked blood vessels in the eyes, which can lead to damage to the retina.

Diagnosis?

Sickle-cell anemia? is typically diagnosed through a blood test. These tests look for the abnormal hemoglobin? (HbS) that characterizes the disease. Additional tests, such as haemoglobin electrophoresis, can confirm the diagnosis? and determine the specific type of SCD. Early diagnosis, such as through newborn screening?, is essential for managing the disease and preventing severe complications.

Treatment

While there is no universal cure for SCD, various treatments can help manage symptoms and reduce complications:

Preventive care:

• routine vaccinations (pneumococcal, Haemophilus influenzae, hepatitis? B)
• folic acid supplements.

Disease-modifying therapy:

• hydroxyurea: a medication that reduces the frequency of pain? crises and the need for blood transfusions by increasing the production of fetal haemoglobin, which prevents the sickling of red blood cells;
• pain? management: using medications like acetaminophen, ibuprofen, and opioids to relieve pain during crises; and
• blood transfusions: to treat severe anaemia and prevent stroke? by increasing the number of normal red blood cells in circulation.

Treatments that help manage sickle cell disease include supportive care, disease-modifying agents and curative intent treatments.

Supportive care includes:

• Antibiotics: Your provider may give you antibiotics to prevent serious infections.
• Blood transfusions: Transfusions can give you more healthy red blood cells and treat anemia?, sickle cell crises and other complications.

Disease-modifying agents include:

• Hydroxyurea: Hydroxyurea makes blood cells less likely to sickle.
• L-glutamine: L-glutamine can reduce damage to your red blood cells.
• Crizanlizumab: Crizanlizumab (Adakveo®) is a monoclonal antibody treatment that makes red blood cells and blood vessels less sticky.

Curative intent options include:

• Bone marrow transplant (BMT): Bone marrow is replaced with stem cells from a donor without sickle cell disease.
• Gene therapy: There are two types of gene therapy available for sickle cell: Casgevy™ and Lyfgenia™. Casgevy edits a gene in your own cells so you’ll make more normal hemoglobin?. Lyfgenia gives you a working hemoglobin gene.

Curative options:

• bone marrow transplant: a potential cure for some patients, particularly children with severe SCD, by replacing the defective bone marrow with healthy marrow from a donor; and
• gene therapy: emerging treatments that aim to correct the genetic mutation causing SCD, offering hope for a long-term cure.

Complications

SCD can lead to numerous complications, including:

• early mortality especially in individuals without access to care;
• severe infections (e.g. pneumococcal, salmonella);
• stroke?: due to blocked blood flow to the brain, which can cause long-term neurological damage;
• acute? chest syndrome: a life-threatening condition caused by sickle-cells blocking blood flow in the lungs, leading to chest pain?, fever?, and difficulty breathing;
• organ damage: particularly to the spleen, liver, and kidneys, due to repeated blockages and lack of oxygen;
• leg ulcers: chronic?, painful sores on the legs that are difficult to heal;
• priapism; and
• pregnancy complications (maternal and neonatal risks).

Prevention and management

Preventing complications and managing SCD involves regular medical care and lifestyle adjustments:

• regular check-ups: with a health-care provider specializing in SCD to monitor health and manage symptoms;
• vaccinations: to prevent infections, particularly pneumococcal and meningococcal infections;
• healthy lifestyle: including a balanced diet, adequate hydration, and avoiding extreme temperatures to reduce the risk of crises; and
• education and support: for patients and families to understand the disease and its management, including recognizing early signs of complications and knowing when to seek medical help.

For people living with sickle-cell disease, part of good health and well-being includes consideration about sexual and reproductive health.

Providers should talk to patients about sexual and reproductive health and their plans for pregnancy within the context of sickle-cell disease. Women living with sickle-cell disease need integrated care that informs them of the options for care in order to reduce any sickle-cell symptoms. Preventing complications can lead to better outcomes for women and their babies.

When considering pregnancy

Women with sickle-cell disease (SCD) should consider several important factors to ensure a healthy pregnancy and minimize risks. Here are some key considerations:

• counseling about genetic implications and the person’s health status;
• discussing continuing or discontinuing medication and supplements in alignment with the WHO guideline; and
• joining a local sickle-cell disease support group to be connected with others who are going through similar challenges and to access emotional support and practical advice.

When planning pregnancy

For women living with sickle-cell disease, planning for pregnancy will help to ensure good health for themselves and their babies.

Consideration should be given to:

• timing: planning the timing of pregnancy to ensure it occurs when the woman is in the best possible health; and
• emergency planning: developing an emergency plan for managing sickle-cell crises during pregnancy.

WHO response

The World Health Organization (WHO) recognizes SCD as a significant public health issue and works to improve the lives of those affected through various initiatives. WHO’s efforts include:

• raising awareness: about SCD and its impact on global health through campaigns and educational programmes;
• supporting research: to develop new treatments and potential cures, with attention to funding and facilitating clinical trials that include women of reproductive age and in pregnancy, in order to better understand the benefits and risks of treatments in and around the time of pregnancy;
• early diagnosis? and intervention, which can significantly improve outcomes for affected individuals;
• collaborating with governments and organizations: to implement effective SCD management programmes and policies, ensuring access to care and treatment;
• providing guidelines and resources: for health-care providers to improve patient care, including best practices for managing SCD during pregnancy, childbirth, and the interpregnancy period; and
• PEN-Plus: a model that complements the WHO package of essential noncommunicable disease interventions and contributes to reducing premature mortality from severe noncommunicable disease by providing integrated care and services among Africa’s poorest children and young adults.