What Is 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 leave the body without enough healthy red blood cells to carry oxygen to organs and muscles. The unusual shape of these cells also causes them to block blood vessel flow, reduce oxygen delivery to tissues, and cause 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 remains challenging for many people, particularly those with sickle cell anemia. Therapy advances, though, have led to better control of symptoms and improved quality of life. Researchers are also working on potential cures.

The most effective sickle cell disease care continues to come from teams that can offer the full range of specialists and support required. Learn more about treatments offered by the Comprehensive Sickle Cell Program at Penn Medicine.

What Causes Sickle Cell Anemia and Sickle Cell Disease?

Sickle cell disease is caused by genetic variants, or changes, in the HBB gene passed from parents to children. The gene helps produce hemoglobin (Hb), the molecule on red blood cells that carries oxygen.

Everyone has two copies of the HBB gene — one from each parent. In order to develop sickle cell disease, a person must inherit a changed HBB gene from both parents. People with a sickle cell HBB gene from just one parent have sickle cell trait. They typically don’t experience symptoms, but can potentially pass the same trait on to their children.

Sickle cell disease is most commonly found in families of African ancestry. Families of Saudi Arabian, Indian, Hispanic, and Mediterranean descent may also have it.

Types of Sickle Cell Disease

While sickle cell anemia is the most common form of sickle cell disease, there are other types. The types differ based on how genetic changes affect beta-globin, a key part of hemoglobin.

To carry oxygen and work properly, each hemoglobin molecule needs two beta-globin blocks. Some changes to the HBB gene cause unusual versions of beta-globin to form — hemoglobin S (HbS) and hemoglobin C (HbC) are the most common. These beta-globin changes affect the hemoglobin molecule and cause sickle-shaped cells.

Various combinations of beta-globin cause different types of sickle cell disease:

  • Sickle cell anemia: With this form, hemoglobin S takes up both beta-globin spots. Sickle cell anemia usually causes the most severe symptoms among the sickle cell disorders. It’s also referred to as HbSS.
  • Sickle-hemoglobin C: With this version, normal beta-globin is replaced by one hemoglobin S and one hemoglobin C. Milder symptoms typically result. The condition is also called HbSC.
  • Hemoglobin S-beta thalassemia: With this type, one beta-globin block is replaced by hemoglobin S. The other produces less beta-globin than normal due to genetic changes tied to thalassemia. If some beta-globin still gets made, it’s called HbS beta plus thalassemia. If none is made, it’s called HbS beta zero thalassemia. Less beta-globin often makes symptoms worse.

Other HBB changes lead to not enough beta-globin getting made. This shortage causes a different red blood cell condition called beta thalassemia, a type of thalassemia.

Sickle Cell Disease Symptoms

People with more severe sickle cell disease often start experiencing symptoms as newborns. The disease can affect many parts of the body and symptoms can get worse over time.

Symptoms and complications of sickle cell disease include:

  • Anemia: Not having enough red blood cells can lead to anemia, marked by fatigue and shortness of breath.
  • Complications from blood vessel blockages: Sickled red blood cells can get stuck in blood vessels, causing temporary but severe pain flares called vaso-occlusive episodes (VOEs). These most commonly occur in the limbs, chest, and back. Blocked blood vessels can also lead to problems in the eyes, kidneys, spleen, and legs. They can cause an emergency called acute chest syndrome and the eventual death of bone tissue. They can also trigger a stroke in the brain.
  • Blood clots: Misshapen red blood cells can cause blood clots to form, which may pose a health risk.
  • Chronic pain: As people with sickle cell disease grow older, they may develop chronic pain, for reasons that remain unclear. This type of pain is ongoing and long-lasting.
  • Other organ damage: Without enough red blood cells, the body may not have enough oxygen, causing particular stress on the heart, lungs, and kidneys. Damaged red blood cells can also gather in the liver and cause problems.
  • Pregnancy: Sickle cell disease poses certain challenges during pregnancy. The disease can temporarily grow more severe, with more frequent pain. It can also increase the chances of premature birth and low birthweight. People with sickle cell disease need extra attention while pregnant to protect their health and their baby’s.

Diagnosing Sickle Cell Anemia and Related Diseases

Since 2006, all U.S. states have screened newborns for sickle cell disease using a basic blood test. The test also looks for the sickle cell trait.

While many people with sickle cell anemia get diagnosed in childhood, milder disease may not get noticed right away. A blood test can look for any changes to hemoglobin.

Sickle Cell Disease Treatment

People with more severe forms of sickle cell disease usually need to take one or more medications. Many of these medications help prevent or reduce VOEs—some also protect organs. Researchers are developing additional options in clinical trials.

Sickle cell disease often involves personalized pain relief plans. These plans can include strategies to use at home and pain relievers, including prescription medications. Sometimes people still need to seek care in the emergency room or at specialized clinics to relieve their pain.

Researchers are working on newer treatments for sickle cell disease. One option would restore the genetic information needed to produce normal red blood cells. Several trials are underway to test this gene therapy, with the goal of providing better symptom control and possibly even a cure.

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Penn Programs & Services for Sickle Cell Disease

Red blood cells affected by sickle cell disease.

Comprehensive Sickle Cell Program

Get sickle cell care focused on your needs. Our expert hematologists offer multidisciplinary care and the latest advances, to help you manage and prevent the complications of sickle cell disease.

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