Sickle Cell Disease

Sickle cell disease (SCD) is a genetic blood disorder. It causes your red blood cells to form into a “C” shape — like a crescent moon, or a farm tool called a sickle. These sickled blood cells can stick together and keep oxygen from getting to your tissues and organs. This can cause episodes of pain and life-threatening complications.

You get sickle cell disease by inheriting two copies of a gene that makes a version of hemoglobin that doesn’t work properly. This causes sickling. Hemoglobin is the part of your blood that carries oxygen.

The symptoms and complications of sickle cell disease can start at any age. Babies can start having symptoms at 5 or 6 months old. Young kids can have frequent pain, anemia, blood clots and strokes.

Symptoms of sickle cell disease

Symptoms of sickle cell could include:

• Episodes of severe pain— most often in your back, legs, arms and sometimes in your chest
• Fatigue
• Paleness
• Weakness
• Yellowish skin and whites of your eyes (jaundice)
• Swollen joints
• Painful, swollen hands and feet (dactylitis)
• Stroke

Signs and symptoms of SCD can be different for each person. They might be mild or severe.

Sickle cell disease causes

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.

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.

Is sickle cell disease dominant or recessive?

Many people think of sickle cell disease as autosomal recessive. This is because you usually have to have two abnormal copies of the HBB gene to have symptoms.

But sickle cell disease is actually an example of incomplete dominance or codominance. People with one abnormal HBB gene have both sickled and normal red blood cells. And, in certain circumstances, they can have symptoms of SCD.

Risk factors

You’re more likely to carry gene variants for sickle cell disease if you or your ancestors (parents, grandparents and other direct relatives) are from:

• Africa
• Central or South America
• Mediterranean countries
• The Middle East
• South Asia

Complications of sickle cell disease

Pain is the most common complication of sickle cell disease. Blood cells can get stuck and block your blood flow. This prevents oxygen from getting to your tissues and can cause pain episodes called sickle cell crises, vaso-occlusive crises (VOC) or vaso-occlusive episodes (VOE). The pain might be temporary or last for several months. Sickle cell crises can come with other symptoms, like dizziness, fatigue, weakness or shortness of breath.

Other complications of SCD include:

• Anemia
• Acute chest syndrome
• Avascular necrosis
• Blood clots, including deep vein thrombosis and pulmonary embolism
• Dactylitis
• Infections like pneumonia and meningitis
• Leg ulcers
• Liver, kidney and heart damage
• Pulmonary hypertension
• Priapism
• Sleep apnea
• Stroke
• Vision loss and other vision problems

If you’re pregnant and have sickle cell, you might be at higher risk for miscarriage, preeclampsia, having a baby with low birth weight and other pregnancy complications.

How doctors diagnose sickle cell disease

In many countries, including the U.S., hospitals test all babies for sickle cell disease. This is a heel prick (blood) test that’s part of routine newborn screenings.

Your healthcare provider can also diagnose sickle cell disease before your baby is born using prenatal testing. These tests include chorionic villus sampling and amniocentesis.

Is there a cure for sickle cell disease?

The only potential cure for sickle cell disease is a bone marrow transplant. This procedure replaces your bone marrow (where red blood cells are made) with a donor’s. But you have to find a donor who’s a good match (often a close family member, like a sibling). It’s also a risky procedure.

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.

When should I see my healthcare provider?

During a crisis, you can try to manage the pain at home by taking pain relievers (ask your provider which they recommend), drinking plenty of fluids and applying heat to the area. If you can’t manage the pain at home, contact your provider or go to the emergency room.

Sickle cell disease can lead to life-threatening complications. Call 911 (or your local emergency services number) or go to the nearest emergency room if you or your child has:

• Severe pain
• Symptoms of severe anemia, including fatigue, dizziness and shortness of breath
• Fever
• Vision problems
• Difficulty breathing
• Erection lasting for four or more hours
• Symptoms of acute chest syndrome, including chest pain, coughing and fever
• Symptoms of stroke, including sudden weakness, numbness on one side of your body and confusion

What can I expect if my child has sickle cell disease?

If your child has sickle cell disease, they’ll probably go through good patches and bad ones. They might have frequent episodes of pain or fatigue, or need to miss school more often than other kids.

Not all kids have frequent symptoms. But you’ll need to know what serious symptoms to look out for and when to take them for emergency care.

How can I take care of my child with sickle cell disease?

There are many ways you can support your child:

• Always trust that they know their body. Take them seriously if they tell you they’re in pain or that they’re so tired that they can’t get out of bed.
• Make sure they get plenty of fluids at the first signs of an episode.
• Learn what kinds of things might trigger a crisis. This could be heat or cold, certain activities, stress, injuries or other factors.
• You can use heat or pain relievers to help manage mild pain at home. Ask your child’s provider what medications are safe to give them (and how much).
• Ask their healthcare providers what serious symptoms to look out for. Know when to take your child to the hospital or call 911.

How do I manage sickle cell disease?

Ways you can manage sickle cell disease include:

• Attend all scheduled appointments with your provider. Let them know about any concerns and whether you feel your symptoms are manageable.
• Ask your provider about the best ways to prevent infections. Talk to them about which vaccines they recommend.
• Drink enough fluids to stay hydrated.
• Work with your provider to keep your blood pressure in a safe range.
• Be physically active, but don’t overdo it. Ask your provider what the right amount of activity is for you.
• Don’t smoke or vape.
• Talk to your provider about what medicines are safe to take. Some may increase your risk of blood clots.
• Take care of your mental health. Lifelong health conditions can take a toll on your mental and physical well-being.
• Talk to your provider if you’re pregnant or plan to become pregnant. They can help reduce your risk of complications.

What’s the life expectancy of sickle cell disease?

Studies suggest that people with sickle cell disease who haven’t had a stem cell transplant have a life expectancy of around 54 years. This estimate may not take into account new treatments that could be developed during your lifetime.

Can you prevent sickle cell disease?

Since you’re born with sickle cell disease, there’s no way to prevent it. If you or your partner has sickle cell disease or sickle cell trait, you can talk to a genetic counselor about the possibility that your future children would have SCD.

What’s the difference between sickle cell disease and sickle cell trait?

If you have sickle cell disease, you have two abnormal copies of the HBB gene. You’ll have symptoms and are at risk for severe complications. If you have sickle cell trait, you only have one abnormal HBB gene. You probably won’t have symptoms or complications.