Sickle cell disease

Sickle cell disease is a group of genetic blood disorders that affect the shape and function of red blood cells. These changes can leave the body without enough healthy red blood cells to carry oxygen. The unusual shape of these cells can also block blood flow, reduce oxygen delivery to tissues, and lead to serious complications. Sickle cell anemia is the most severe and well-known type of sickle cell disease.

Healthy red blood cells are round, smooth, and flexible. Red blood cells damaged by sickle cell disease can:

• End up looking like a sickle (a crescent-shaped farming tool)
• Become sticky, stiff, and fragile
• Get stuck, damaging blood vessels and blocking blood supply
• Die early, preventing them from delivering all the oxygen the body needs

Sickle cell disease is a lifelong condition that can cause serious health problems, particularly for people with sickle cell anemia. However, advances in treatment have helped many people better manage symptoms, prevent complications, and improve their quality of life. Researchers are also developing promising new therapies, including treatments with the potential to cure some people with sickle cell disease.

At Penn Medicine, we provide compassionate sickle cell disease care. Whether you’re transitioning from pediatric to adult care or looking for a new approach after years of managing the condition, our team works closely with you to support your health and well-being. Our researchers and clinicians are dedicated to providing the most advanced options including cell and gene therapies.

Symptoms of sickle cell disease often begin during infancy and can vary from person to person.

Common symptoms include:

• Severe pain, often affecting the arms, legs, chest, back, or abdomen
• Fatigue and weakness due to anemia
• Shortness of breath
• Swelling of the hands and feet
• Frequent infections
• Delayed growth and puberty in children
• Vision problems
• Serious complications from blocked blood flow, including blood clots, stroke, and damage to organs and tissues

Sickle cell disease is caused by genetic variants, or changes, that are passed from parents to children through the HBB gene. This gene provides instructions for making beta-globin, a protein that is part of hemoglobin, the molecule in red blood cells that carries oxygen throughout the body.

Everyone has two copies of the HBB gene, one inherited from each parent. To develop sickle cell disease, a person must inherit an altered HBB gene from both parents. People who inherit a changed HBB gene from only one parent have sickle cell trait. They usually do not experience symptoms of sickle cell disease, but they can pass the trait on to their children.

Sickle cell disease is most common among people of African ancestry. It is also more common in people with ancestry from the Mediterranean region, the Middle East, India, and parts of Central and South America.

Sickle cell anemia is the most common form of sickle cell disease, but several other forms exist. These conditions differ based on the type of inherited HBB gene change.

Different HBB gene changes can produce abnormal forms of hemoglobin, most commonly hemoglobin S (HbS) and hemoglobin C (HbC). Abnormal hemoglobin can affect the shape and flexibility of red blood cells and contribute to sickle cell disease.

Common types of sickle cell disease include:

• Sickle cell anemia (HbSS): Both HBB genes encode hemoglobin S. This is the most common and often the most severe form of sickle cell disease.
• Hemoglobin SC disease (HbSC): One HBB gene encodes hemoglobin S and the other encodes hemoglobin C. Symptoms are often milder than those of HbSS, though serious complications can still occur.
• Hemoglobin S-beta thalassemia: One HBB gene encodes hemoglobin S, while the other carries a beta-thalassemia mutation. If some beta-globin is produced, the condition is called HbS beta plus thalassemia. If no beta-globin is produced, it is called HbS beta zero thalassemia. Symptoms can vary, but HbS beta zero thalassemia is generally more severe.

Other HBB gene variants that reduce beta-globin production without producing hemoglobin S can cause beta-thalassemia, a separate inherited blood disorder.

Newborn screening throughout the United States includes a blood test for sickle cell disease. This test can also identify the sickle cell trait. While many people are diagnosed during infancy or childhood, people with milder forms of sickle cell disease may not be diagnosed until later in life. If sickle cell disease is suspected, doctors use additional tests to confirm the diagnosis and determine the type of sickle cell disease.

Specialized tests used to diagnose sickle cell disease include:

• Hemoglobin testing: Blood tests identify abnormal forms of hemoglobin, including hemoglobin S (HbS), and determine the type of sickle cell disease.
• Complete blood count (CBC): This test measures red blood cells, hemoglobin, and other blood cells to check for anemia and other blood abnormalities.
• Genetic testing: Gene testing may be used to confirm the diagnosis, identify changes in the HBB gene, or help with family planning.

Sickle cell disease affects more than your blood. It can impact many parts of your life. At Penn Medicine, specialists from different fields work together to create a care plan that fits your needs.

• A team with specialized experience: Hematologists, nurses, social workers, psychologists, and other experts work together to support your care.
• Care for your whole health: We treat sickle cell disease, help manage pain, monitor for complications, and connect you with other specialists when needed.
• Support at every step: We provide emotional, mental health, and social support to help you manage the challenges of living with sickle cell disease.
• A smooth transition to adult care: We work closely with Children’s Hospital of Philadelphia (CHOP) to help young adults move from pediatric to adult care.
• The latest treatment options: Eligible people may have access to advanced treatments, including stem cell transplantation, gene therapy, and clinical trials.

Our goal is to help you reduce complications, improve your health, and live as fully as possible with sickle cell disease.