What Is Sickle Cell Anemia? Symptoms, Causes, Diagnosis, Treatment, and Prevention
Sickle cell anemia is one of a group of inherited blood disorders marked by flawed hemoglobin, the protein molecule in red blood cells that carries oxygen from the lungs to the tissues in the body. It is the most severe form of sickle cell disease.
Red blood cells that contain normal hemoglobin are disc-shaped and flexible, so they move easily through both large and small blood vessels. People with sickle cell anemia inherit a defective hemoglobin S gene that can cause rigid protein strands to form within red blood cells. This causes the cells to become shaped like a sickle, the farming tool with a semicircular blade like a crescent moon, giving both the cells and the disease their name.
The sickle-cell trait and anemia are more common in Africa, because there is some protection from malaria (an infection endemic to sub-Saharan Africa) in having the sickle-cell trait. The exact mechanism of this is not known, but it is thought that the sickle shape is less able to be infected by the malaria virus, and when it does get infected, the body is better able to detect and remove the infected cell.
These sickle-shaped cells are not flexible and can stick to vessel walls, causing inflammation in the blood vessels and blockages that can stop or slow the flow of blood.
Furthermore, because these sickle-shaped cells cannot change shape easily, they tend to burst apart, and unlike normal blood cells that live about three to four months, sickle cells last only 10 to 20 days.
The body, which is always making new red blood cells to replace the old cells, may have trouble keeping up with how fast the cells are being destroyed. This leads to an overall shortage of red blood cells in the body and, consequently, anemia.
In addition to anemia, the disease can cause other health problems, including infections, stroke, and kidney disease. These health issues can be long-term and can reduce life expectancy.
Pain and fatigue are prominent symptoms of this disorder. The fatigue results from anemia, or a deficiency of healthy red blood cells. The degree of anemia varies among individuals.
Symptoms related to anemia may include the following:
Skin that’s paler than normal
Yellowish skin, eyes, or mouth (jaundice)
Difficulty concentrating
Shortness of breath, especially during exercise
Dark-colored urine
Fever
Weakness
Dizziness
Confusion
Inability to handle physical activity
Enlarged spleen and liver
Increased heart rate
Heart murmur
Although the disease is present at birth, most newborns do not experience problems right away. Symptoms of sickle cell anemia typically start after the fifth or sixth month of life. This is when a baby’s level of fetal hemoglobin, which protects red blood cells from sickling, begins to decline.
Common early symptoms include the following:
Jaundice
Fatigue
Fussiness
Painful swelling of feet and hands (known as dactylitis)
Another major symptom of sickle cell anemia is periodic episodes of pain, known as sickle cell crises. During these events, sickle-shaped red blood cells block blood flow to the limbs and organs. The pain varies in intensity and can last for a few hours to a few weeks. Some people have only a few pain crises a year. Others may experience a dozen or more each year.
The severity of symptoms varies from person to person and changes over time. Some people have mild symptoms, while others require frequent hospitalizations to treat more serious symptoms and complications.
According to the Centers for Disease Control and Prevention (CDC), you should seek medical help immediately if you experience any of the following:
Fever above 101 degrees F
Difficulty breathing
Pain in the chest
Swelling of the abdomen
Severe headache
Sudden weakness or loss of feeling and movement
Seizures
Painful erection of the penis lasting more than four hours
To have sickle cell anemia, a person must inherit two sickle hemoglobin genes, one from each parent. People with sickle cell trait (meaning they inherited only one sickle hemoglobin gene) generally don’t have symptoms of sickle cell disease, but they can pass the sickle hemoglobin gene on to their children.
Having a family history of sickle cell disease increases your risk for the disease.
Sickle cell anemia is more common in certain groups. In the United States, sickle cell anemia is most prevalent among Black Americans.
Sickle cell anemia is diagnosed through blood testing.
A blood test will demonstrate the following situations:
Your hemoglobin is normal.
You have sickle cell anemia or another sickle cell disease.
You have sickle cell trait (meaning you are a carrier for the disease).
In the United States, all newborns are screened for sickle cell status. Early diagnosis is important to better prevent complications.
Doctors can also diagnose sickle cell anemia before a baby is born through prenatal screening, using a sample of amniotic fluid or tissue taken from the placenta. This testing can be done as early as 8 to 10 weeks into the pregnancy.
Prognosis of Sickle Cell Anemia
Sickle cell anemia worsens over time, but treatments can prevent complications and lengthen the lives of those with the condition.
People who have sickle cell anemia have a reduced life expectancy. While some people can remain without symptoms for years, some may not survive beyond infancy or early childhood.
New treatments, however, are improving life expectancy and quality of life for those with sickle cell anemia. As little as 50 years ago, almost 15 percent of children born with sickle cell anemia died before age 2, and many more died as teenagers.
According to a study published in 2019, the mortality rate of infants and children with sickle cell disease in the United States has decreased due to newborn screening, immunizations, use of antibiotics to prevent infections, and use of the drug hydroxyurea (Hydrea).
Today, people with sickle cell anemia can survive into their fifties and beyond with optimal management of their disease.
Sickle cell anemia is generally a lifelong condition, and the only cure is a blood or bone marrow transplant (also called a stem cell transplant). According to the CDC, these transplants are limited to children with severe cases of the disease who have experienced minimal organ damage.
Stem cell transplants are riskier in adults. According to Be the Match, a bone marrow registry, adults with severe sickle cell anemia are able to get a bone marrow transplant only if they join a clinical trial.
However, researchers are looking at new ways to help more people who have sickle cell anemia get a transplant, including blood and bone marrow transplant techniques for children and adults who can’t find a matched donor in the family.
Researchers are also exploring ways that genetic therapies might lead to new treatments or a cure.
Daily penicillin for children to prevent related possible infections
Routine vaccinations to prevent possible infections
Hydroxyurea, which helps prevent red blood cells from sickling and improves anemia
Crizanlizumab (Adakveo), a medicine administered through an IV in a vein and approved in 2019 by the U.S. Food and Drug Administration (FDA) for pain crises
Glutamine (Endari), a drug FDA-approved to help reduce acute complications of sickle cell disease
Lifestyle measures, including drinking plenty of water and avoiding extreme physical exertion
Pain management can be challenging for individuals with sickle cell anemia. While research is limited, there is some evidence that individuals might benefit from nonpharmacological pain interventions. In June 2020, the American Society of Hematology (ASH) published treatment guidelines for sickle cell disease pain. The ASH panel recommended massage, yoga, transcutaneous electrical nerve stimulation (TENS), virtual reality, and guided audiovisual relaxation in addition to standard pharmacological management for treatment of acute pain.
In addition, a study published in 2020 suggests that acupuncture may be a useful add-on therapy for pain management for children with sickle cell anemia.
A medication called voxelotor (Oxbryta) was approved by the FDA in 2019 to treat sickle cell anemia, but the administration announced in September 2024 that Oxbryta was being voluntarily withdrawn by Pfizer because of safety concerns.
There is no known way to prevent sickle cell anemia. However, you can find out if you carry the gene mutation through a simple blood test. If you don’t have sickle cell anemia but people in your family do, you may have inherited one sickle cell gene; this is referred to as sickle cell trait. If you carry the gene, your chances increase for having a child with either the disease or sickle cell trait.
To be born with sickle cell anemia, a child must inherit two sickle cell gene mutations, one from each parent.
If you carry the mutated gene and your partner carries the mutated gene, there is a 1 in 4 chance that your child will have sickle cell anemia; a 1 in 2 chance they will become a carrier; and a 1 in 4 chance they will not acquire the disease.
If one of you carries the trait, there is a 1 in 2 chance that your child will also carry the trait — but there is no chance they can get the disease.
Genetic counselors can help you review your family history, navigate your blood test results, and guide you in making informed decisions with regard to family planning.
A few simple steps can help prevent and reduce the number of pain crises:
Drinking plenty of water
Avoiding getting too hot or cold
Avoiding exposure to high altitudes
Avoiding places or situations where there might be low oxygen levels, such as mountain climbing or extremely intense exercise
People with sickle cell anemia are at a greater risk than those without the condition for problems, including conditions related to the heart, lungs, and kidneys.
Complications include the following:
Acute chest syndrome, a medical emergency caused by sickling of the blood vessels of the lungs, which results in damaged lung tissue, chest pain, fever, and difficulty breathing
Acute pain crisis, which involves sharp, intense, stabbing, or throbbing pain that occurs almost anywhere in the body and is brought on by sickle cells blocking blood flow
Chronic pain
Organ damage due to sickle cells blocking blood flow, thus depriving organs of blood and oxygen
Delayed growth and puberty
Eye problems, such as injury to blood vessels in the eye that could result in vision loss
Gallstones
Heart problems, including coronary heart disease and pulmonary hypertension
Infections due to damage to the spleen
Joint problems
Kidney problems, including chronic kidney disease
Leg ulcers
Liver problems
Increased risk of miscarriage, premature birth, and low-weight babies
Priapism, which is a prolonged, painful erection caused by sickle cells blocking blood flow out of the erect penis
Severe anemia, which can be potentially life-threatening
Stroke
Sudden exercise death
Having sickle cell anemia increases your risk for developing severe illness from COVID-19. People with sickle cell anemia often have underlying cardiopulmonary issues that may lead to poor outcomes if they become infected with the virus.
According to the World Health Organization, about 300,000 infants are born with hemoglobin disorders, including sickle cell anemia, each year. More than 75 percent of the newborns born with the disease are born in sub-Saharan Africa. In the United States, sickle cell disease, including sickle cell anemia, affects approximately 100,000 Americans.
Sickle cell disease occurs in 1 of every 365 Black Americans. The disease occurs in 1 of every 16,300 Hispanic Americans.
Additionally, about 1 in 13 Black children in the United States are born with sickle cell trait.
The condition also affects people of Middle Eastern, Asian, Indian, and Mediterranean descent.
