Sickle cell disease is a group of inherited red blood cell disorders that affect hemoglobin, the protein that carries oxygen through the body. Normally, red blood cells are disc-shaped and flexible enough to move easily through the blood vessels. In sickle cell disease, red blood cells become crescent- or “sickle”-shaped due to a genetic mutation. These sickled red blood cells do not bend or move easily and can block blood flow to the rest of the body.

The blocked blood flow through the body can lead to serious problems, including stroke, eye problems, infections, and episodes of pain called pain crises.

Sickle cell disease is a lifelong illness. Until recently, a bone marrow transplant was the only cure for sickle cell disease. However, in December 2023, the U.S. Food and Drug Administration approved two new therapies to treat the disease. One approach adds a gene to the body and the other makes changes to a gene that is already in the body. NHLBI researchers are continuing to explore treatments that impact genes, but there are other types of treatments that can reduce symptoms and prolong life. If you have sickle cell disease, your healthcare team will work with you on a treatment plan to reduce your symptoms and manage the condition.

The condition affects more than 100,000 people in the United States and 20 million people worldwide. In the United States, most people who have sickle cell disease are of African ancestry or identify themselves as Black:

• About 1 in 13 Black or African American babies are born with sickle cell trait.
• About 1 in every 365 Black or African American babies are born with sickle cell disease.

Many people who come from Hispanic, Southern European, Middle Eastern, or Asian Indian backgrounds also have sickle cell disease.

Sickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disease have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle, or crescent, shape.

Signs and symptoms of sickle cell disease usually begin in early childhood. Characteristic features of this disorder include a low number of red blood cells (anemia), repeated infections, and periodic episodes of pain. The severity of symptoms varies from person to person. Some people have mild symptoms, while others are frequently hospitalized for more serious complications.

The signs and symptoms of sickle cell disease are caused by the sickling of red blood cells. When red blood cells sickle, they break down prematurely, which can lead to anemia. Anemia can cause shortness of breath, fatigue, and delayed growth and development in children. The rapid breakdown of red blood cells may also cause yellowing of the eyes and skin, which are signs of jaundice. Painful episodes can occur when sickled red blood cells, which are stiff and inflexible, get stuck in small blood vessels. These episodes deprive tissues and organs, such as the lungs, kidneys, spleen, and brain, of oxygen-rich blood and can lead to organ damage. A particularly serious complication of sickle cell disease is high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension), which can lead to heart failure. Pulmonary hypertension occurs in about 10 percent of adults with sickle cell disease.

People who have sickle cell disease have abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in their red blood cells. Hemoglobin is a protein in red blood cells that carries oxygen throughout the body. People who have sickle cell disease inherit two abnormal hemoglobin genes, one from each parent.

The types of sickle cell disease include the following:

• Hemoglobin Sβ0 thalassemia
• Hemoglobin Sβ+ thalassemia
• Hemoglobin SC
• Hemoglobin SD
• Hemoglobin SE
• Hemoglobin SS

In all types of sickle cell disease, at least one of the two abnormal genes causes a person’s body to make hemoglobin S. When a person has two hemoglobin S genes (hemoglobin SS), the disease is called sickle cell anemia. This is the most common and often most severe type of sickle cell disease. Hemoglobin SC disease and hemoglobin Sβ thalassemia are two other common types of sickle cell disease. Hemoglobin SD and hemoglobin SE are much less common.

Sickle cell disease affects millions of people worldwide. It is most common among people whose ancestors come from Africa; Mediterranean countries such as Greece, Turkey, and Italy; the Arabian Peninsula; India; and Spanish-speaking regions in South America, Central America, and parts of the Caribbean.

Sickle cell disease is the most common inherited blood disorder in the United States, affecting an estimated 100,000 Americans. The disease is estimated to occur in 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans.

In the United States, most people who have sickle cell disease are of African ancestry or identify themselves as Black.

• About 1 in 13 Black or African American babies are born with sickle cell trait.
• About 1 in every 365 Black or African American babies are born with sickle cell disease.

Many people who come from Hispanic, Southern European, Middle Eastern, or Asian Indian backgrounds also have sickle cell disease.

About 100,000 people in the United States have sickle cell disease.

Sickle cell disease is inherited, meaning that it runs in families. People who have sickle cell disease inherit two faulty hemoglobin genes, called hemoglobin S — one from each parent.

A person has sickle cell trait when the hemoglobin S gene is inherited from only one parent and a normal hemoglobin gene — hemoglobin A — is inherited from the other. People who have sickle cell trait are generally healthy.

If someone has sickle cell trait, they are a carrier of the hemoglobin S gene. That means they can pass it on when they have a child.

If the child’s other parent also has sickle cell trait or another faulty hemoglobin gene, such as beta (β) thalassemia, hemoglobin C, hemoglobin D, or hemoglobin E, that child has a chance of having sickle cell disease. That is because the child could inherit a faulty hemoglobin gene from each parent.

Inheritance pattern for sickle cell disease

In the image above, each parent has one normal hemoglobin A gene and one hemoglobin S gene, which means each of their children has:

• A 25%, or 1 in 4, chance of inheriting two normal hemoglobin A genes. This child does not have sickle cell trait or disease.
• A 50%, or 1 in 2, chance of inheriting one normal hemoglobin A gene and one hemoglobin S gene. This child has sickle cell trait.
• A 25%, or 1 in 4, chance of inheriting two hemoglobin S genes. This child has sickle cell disease.

It is important to keep in mind that each time this couple has a child, the chances of that child having sickle cell disease remain the same. In other words, if the first child has sickle cell disease, there is still a 25% chance that the second child will also have the disease. Both boys and girls can inherit sickle cell trait, sickle cell disease, or normal hemoglobin.

If a person wants to know whether they carry a sickle hemoglobin gene, a doctor can order a blood test to find out.

What is a “sickled cell”?

Red blood cells with normal hemoglobin are disc-shaped and flexible so that they can move easily through large and small blood vessels to deliver oxygen throughout the body.

Sickled hemoglobin is not like normal hemoglobin. Sickle-shaped red blood cells are not flexible and can stick to vessel walls, causing blockages that slow or stop the flow of blood. The abnormal hemoglobin can also cause stiff strands to form within the red blood cell. These stiff strands can change the shape of the cell, causing the sickled red blood cell that gives the disease its name.

The sickle-shaped cells cannot deliver oxygen to the rest of the body. This can cause attacks of sudden severe pain, called pain crises. These pain crises can occur without warning, and a person who has them often needs to go to the hospital for effective treatment.

Because sickle cells cannot easily change shape, they also tend to burst apart. Normal red blood cells live about 90 to 120 days, but sickle cells last only 10 to 20 days. The body is always making new red blood cells to replace the old cells. However, in sickle cell disease, the body may have trouble keeping up with how fast the cells are being destroyed. Because of this, the number of red blood cells is usually lower than in people without sickle cell disease. This condition, called anemia, can cause a person to have less energy.

Sickle cell disease is a group of inherited red blood cell disorders.

What do we know about heredity and sickle cell disease?

Sickle cell disease is the most common inherited blood disorder in the United States. Approximately 100,000 Americans have the disease.

In the United States, sickle cell disease is most prevalent among African Americans. About one in 12 African Americans and about one in 100 Hispanic Americans carry the sickle cell trait, which means they are carriers of the disease.

Sickle cell disease is caused by a mutation in the hemoglobin-Beta gene found on chromosome 11. Hemoglobin transports oxygen from the lungs to other parts of the body. Red blood cells with normal hemoglobin (hemoglobin-A) are smooth and round and glide through blood vessels.

In people with sickle cell disease, abnormal hemoglobin molecules - hemoglobin S - stick to one another and form long, rod-like structures. These structures cause red blood cells to become stiff, assuming a sickle shape. Their shape causes these red blood cells to pile up, causing blockages and damaging vital organs and tissue.

Sickle cells are destroyed rapidly in the bodies of people with the disease, causing anemia. This anemia is what gives the disease its commonly known name - sickle cell anemia.

The sickle cells also block the flow of blood through vessels, resulting in lung tissue damage that causes acute chest syndrome, pain episodes, stroke and priapism (painful, prolonged erection). It also causes damage to the spleen, kidneys and liver. The damage to the spleen makes patients - especially young children - easily overwhelmed by bacterial infections.

A baby born with sickle cell disease inherits a gene for the disorder from both parents. When both parents have the genetic defect, there's a 25 percent chance that each child will be born with sickle cell disease.

If a child inherits only one copy of the defective gene (from either parent), there is a 50 percent chance that the child will carry the sickle cell trait. People who only carry the sickle cell trait typically don't get the disease, but can pass the defective gene on to their children.

New Treatments Prolong Life:

Until recently, people with sickle cell disease were not expected to survive childhood. But today, due to preventive drug treatment, improved medical care and aggressive research, half of sickle cell patients live beyond 50 years.

Treatments for sickle cell include antibiotics, pain management and blood transfusions. A new drug treatment, hydroxyurea, which is an anti-tumor drug, appears to stimulate the production of fetal hemoglobin, a type of hemoglobin usually found only in newborns. Fetal hemoglobin helps prevent the "sickling" of red blood cells. Patients treated with hydroxyurea also have fewer attacks of acute chest syndrome and need fewer blood transfusions.

Bone Marrow Transplantation: The Only Cure:

Currently the only cure for sickle cell disease is bone marrow transplantation. In this procedure a sick patient is transplanted with bone marrow from healthy, genetically compatible sibling donors. However only about 18 percent of children with sickle cell disease have a healthy, matched sibling donor. Bone marrow transplantation is a risky procedure with many complications.

Gene Therapy Offers Promise of a Cure:

Researchers are experimenting with attempts to cure sickle cell disease by correcting the defective gene and inserting it into the bone marrow of those with sickle cell to stimulate production of normal hemoglobin. Recent experiments show promise.

Researchers used bioengineering to create mice with a human gene that produces the defective hemoglobin causing sickle cell disease. Bone marrow containing the defective hemoglobin gene was removed from the mice and genetically "corrected" by the addition of the anti-sickling human beta-hemoglobin gene. The corrected marrow was then transplanted into other mice with sickle cell disease. The genetically corrected mice began producing high levels of normal red blood cells and showed a dramatic reduction in sickled cells. Scientists are hopeful that the techniques can be applied to human gene transplantation using autologous transplantation, in which some of the patient's own bone marrow cells would be removed and genetically corrected.

Is there a test for sickle cell disease?

Doctors diagnose sickle cell through a blood test that checks for hemoglobin S - the defective form of hemoglobin. To confirm the diagnosis, a sample of blood is examined under a microscope to check for large numbers of sickled red blood cells - the hallmark trait of the disease.

In more than 40 states, testing for the defective sickle cell gene is routinely performed on newborns.

Sickle cell disease can also be detected in an unborn baby. Amniocentesis, a procedure in which a needle is used to take fluid from around the baby for testing, can show whether the fetus has sickle cell disease or carries the sickle cell gene. If the test shows that the child will have sickle cell disease, some parents may choose not to continue the pregnancy. Genetic counselors can help parents make these difficult decisions.

A new technique used in conjunction with in vitro fertilization, called pre-implantation genetic diagnosis (PGD), enables parents who carry the sickle cell trait to test embryos for the defective gene before implantation, and to choose to implant only those embryos free of the sickle cell gene.

Normal Function

The HBB gene provides instructions for making a protein called beta-globin. Beta-globin is a component (subunit) of a larger protein called hemoglobin, which is located inside red blood cells. In adults, hemoglobin consists of four protein subunits: usually two subunits of beta-globin and two subunits of a protein called alpha-globin, which is produced from another gene called HBA. Each of these protein subunits is attached (bound) to an iron-containing molecule called heme; the iron in the center of each heme can bind to one oxygen molecule. Hemoglobin within red blood cells binds to oxygen molecules in the lungs. These cells then travel through the bloodstream and deliver oxygen to tissues throughout the body.

Health Conditions Related to Genetic Changes

Beta thalassemia

Hundreds of variants (also known as mutations) in the HBB gene have been found to cause beta thalassemia. Most of the variants involve a change in a single DNA building block (nucleotide) within or near the HBB gene. Other variants insert or delete a small number of nucleotides in the HBB gene.

HBB gene variants that decrease beta-globin production result in a condition called beta-plus (β+) thalassemia. Variants that prevent cells from producing any beta-globin result in beta-zero (β0) thalassemia.

Problems with the subunits that make up hemoglobin, including low levels of beta-globin, reduce or eliminate the production of this molecule. A lack of hemoglobin disrupts the normal development of red blood cells. A shortage of mature red blood cells can reduce the amount of oxygen that is delivered to tissues to below what is needed to satisfy the body's energy needs. A lack of oxygen in the body's tissues can lead to poor growth, organ damage, and other health problems associated with beta thalassemia.

Methemoglobinemia, beta-globin type

Variants in the HBB gene have been found to cause methemoglobinemia, beta-globin type, which is a condition that alters the hemoglobin within red blood cells. These variants often affect the region of the protein that binds to heme. For hemoglobin to bind to oxygen, the iron within the heme molecule needs to be in a form called ferrous iron (Fe2+). The iron within the heme can change to another form of iron called ferric iron (Fe3+), which cannot bind to oxygen. Hemoglobin that contains ferric iron is known as methemoglobin and is unable to efficiently deliver oxygen to the body's tissues.

In methemoglobinemia, beta-globin type, variants in the HBB gene alter the beta-globin protein and promote the heme iron to change from ferrous to ferric. This altered hemoglobin gives the blood a brown color and causes a bluish appearance of the skin, lips, and nails (cyanosis). The signs and symptoms of methemoglobinemia, beta-globin type are generally limited to cyanosis, which does not cause any health problems. However, in rare cases, severe methemoglobinemia, beta-globin type can cause headaches, weakness, and fatigue.

Sickle cell disease

Sickle cell anemia (also called homozygous sickle cell disease or HbSS disease) is the most common form of sickle cell disease. This form is caused by a particular variant in the HBB gene that results in the production of an abnormal version of beta-globin called hemoglobin S or HbS. In this condition, hemoglobin S replaces both beta-globin subunits in hemoglobin.

The variant that causes hemoglobin S changes a single protein building block (amino acid) in beta-globin. Specifically, the amino acid glutamic acid is replaced with the amino acid valine at position 6 in beta-globin, written as Glu6Val or E6V. Replacing glutamic acid with valine causes the abnormal hemoglobin S subunits to stick together and form long, rigid molecules that bend red blood cells into a sickle (crescent) shape. The sickle-shaped cells die too early, which can lead to a shortage of red blood cells (anemia). The sickle-shaped cells are rigid and can block small blood vessels, causing severe pain and organ damage.

Variants in the HBB gene can also cause other abnormalities in beta-globin, leading to other types of sickle cell disease. These abnormal forms of beta-globin are often designated by letters of the alphabet or sometimes by a name. In these other types of sickle cell disease, just one beta-globin subunit is replaced with hemoglobin S. The other beta-globin subunit is replaced with a different abnormal variant, such as hemoglobin C or hemoglobin E.

In hemoglobin SC (HbSC) disease, the beta-globin subunits are replaced by hemoglobin S and hemoglobin C. Hemoglobin C results when the amino acid lysine replaces the amino acid glutamic acid at position 6 in beta-globin (written Glu6Lys or E6K). The severity of hemoglobin SC disease is variable, but it can be as severe as sickle cell anemia. Hemoglobin E (HbE) is caused when the amino acid glutamic acid is replaced with the amino acid lysine at position 26 in beta-globin (written Glu26Lys or E26K). In some cases, the hemoglobin E variant is present with hemoglobin S. In these cases, a person may have more severe signs and symptoms associated with sickle cell anemia, such as episodes of pain, anemia, and abnormal spleen function.

Other conditions, known as hemoglobin sickle-beta thalassemias (HbSBetaThal), are caused when variants that result in hemoglobin S and beta thalassemia (described above) occur together. Variants that combine sickle cell disease with beta-zero (β0) thalassemia lead to severe disease, while sickle cell disease combined with beta-plus (β+) thalassemia is generally milder.

Other disorders

Hundreds of variations have been identified in the HBB gene. These changes result in the production of different versions of beta-globin. Some of these variations cause no noticeable signs or symptoms and are found when blood work is done for other reasons, while other HBB gene variations may affect a person's health. Two of the most common variants are hemoglobin C and hemoglobin E (described above).

Hemoglobin C (HbC), caused by the Glu6Lys variant in beta-globin, is more common in people of West African descent than in other populations. People who have two hemoglobin C subunits in their hemoglobin, instead of normal beta-globin, have a mild condition called hemoglobin C disease. This condition often causes chronic anemia, in which the red blood cells are broken down prematurely.

Hemoglobin E (HbE), caused by the Glu26Lys variant in beta-globin, is a variant of hemoglobin most commonly found in the Southeast Asian population. When a person has two hemoglobin E subunits in their hemoglobin in place of beta-globin, a mild anemia called hemoglobin E disease can occur. In some cases, the variants that produce hemoglobin E and beta thalassemia (described above) are found together. People with this hemoglobin combination can have signs and symptoms ranging from mild anemia to severe thalassemia major.

Other Names for This Gene

• beta globin
• beta-globin
• HBB_HUMAN
• hemoglobin beta gene
• hemoglobin, beta
• hemoglobin--beta locus

Genomic Location

Sickle cell disease is an inherited disease, which means you are born with it. However, most newborns do not have any problems from the disease until they are about 5 or 6 months of age.

The symptoms of sickle cell disease can vary from person to person and can change over time. How the disease affects your body over time will determine what kind of symptoms you may have.

Early symptoms

• A yellowish color of the skin (jaundice) or whites of the eyes (icterus) that occurs when a large number of red cells undergo hemolysis
• Extreme tiredness or fussiness from anemia
• Painful swelling of the hands and feet, known as dactylitis

Know when to seek emergency medical care

Sickle cell disease can lead to serious and life-threatening health problems. If you think that you or someone else is having any of the following symptoms or complications, seek medical care or call 9-1-1 right away.

• Symptoms of severe anemia: These include extreme tiredness (fatigue), shortness of breath, dizziness, or irregular heartbeat. Splenic sequestration crisis or an aplastic crisis can cause severe anemia symptoms. These conditions can be life-threatening.
• Fever: All children and adults who have sickle cell disease and a fever of more than 101.3 degrees Fahrenheit, or 38.5 degrees Celsius, must be seen by a healthcare provider and treated with antibiotics right away. Some people will need to be hospitalized.
• Symptoms of acute chest syndrome: These include chest pain, coughing, fever, and shortness of breath. You will need to be admitted to the hospital, where you may receive antibiotics, oxygen therapy, or a blood transfusion.
• Stroke symptoms: Warning signs include sudden weakness, numbness on one side of the body, confusion, or trouble speaking, seeing, or walking.
• Priapism: If you experience an erection that lasts for 4 hours or more, go to the hospital to see a hematologist (a doctor who specializes in blood conditions and diseases) and a urologist (a doctor who specializes in treating conditions of the male reproductive and urinary systems).

The sickled cells that give the disease its name can lead to pain throughout the body and serious damage to organs such as the heart and kidneys. It is important to be aware of the possible complications of sickle cell disease and know when to seek emergency care.

Some complications may be systemwide (affecting many parts of your body at the same time). Other complications affect specific parts of the body.

Complications affecting your whole body

• Acute pain crisis:Also known as sickle cell or vaso-occlusive crisis, this can happen without warning when sickle cells block blood flow. People describe this pain as sharp, intense, stabbing, or throbbing. Pain can strike almost anywhere in the body and in more than one spot at a time. Common areas affected by pain include the abdomen, chest, lower back, or arms and legs. A crisis can be brought on by high altitudes, dehydration, illness, stress, or temperature changes. Often a person does not know what triggers the crisis.,
• Chronic (long-term) pain: Chronic pain is common, but it can be hard to describe. It is usually different from crisis pain or the pain that results from organ damage.
• Delayed growth and puberty: Because of anemia, children who have sickle cell disease may grow and develop more slowly than their peers. They will reach full sexual maturity, but this may be delayed.
• Infections: The spleen is important for protection against certain kinds of infections. If you have sickle cell disease, a damaged spleen raises the risk for certain infections, including chlamydia, Haemophilus influenzae type B, salmonella, and staphylococcus.
• Joint problems: Sickling in the hip bones and, less commonly, the shoulder joints, knees, and ankles can lower oxygen flow and result in a condition called avascular or aseptic necrosis, which severely damages the joints. Symptoms include pain and problems with walking and joint movement. Over time, you may need pain medicines, surgery, or joint replacement.
• Pregnancy problems: Pregnancy can raise the risk of high blood pressure and blood clots in people who have sickle cell disease. The condition also increases the risk of miscarriage, premature birth, and low birth weight babies. Learn more about pregnancy and sickle cell disease.

Complications affecting specific parts of your body

• Acute chest syndrome: Sickling in blood vessels of the lungs can deprive lungs of oxygen. This can damage lung tissue and cause chest pain, fever, and difficulty breathing. Acute chest syndrome is a medical emergency.
• Enlarged spleen: The spleen is an organ that helps your body fight infection and remove unwanted material. It filters your blood and destroys old blood cells. In people who have sickle cell disease, red blood cells may get trapped in the spleen. This makes the spleen quickly grow larger than normal. With red blood cells trapped in the spleen, fewer are available to circulate in the blood, and this can lead to severe anemia. A large spleen may also cause pain in the left side of the belly. A parent can usually feel a spleen that is larger than normal in a child’s belly.
• Eye problems: Sickle cell disease can injure blood vessels in the eye, most often in the retina. Blood vessels in the retina can overgrow, get blocked, or bleed. This can cause the retina to detach, which means it is lifted or pulled from its normal position. These problems can lead to vision loss.
• Gallstones: When red blood cells break down, in a process called hemolysis, they release hemoglobin. Hemoglobin then gets broken down into a substance called bilirubin. Bilirubin can form stones called gallstones that get stuck in the gallbladder. The gallbladder is a small sac-shaped organ beneath the liver that helps with digestion.
• Heart problems: These can include coronary heart disease and pulmonary hypertension. Frequent blood transfusions can lead to heart damage from iron overload.
• Kidney problems: Sickle cell disease may cause the kidneys to have trouble making the urine as concentrated as it should be. This may lead to a need to urinate often and to bedwetting or uncontrolled urination during the night. These problems often start in childhood.
• Leg ulcers: Sickle cell ulcers are sores that usually start small and then get larger and larger. Some ulcers will heal quickly, but others may not heal and may last for long periods of time. Some ulcers return even after healing. People who have sickle cell disease usually do not get ulcers until after age 10.
• Liver problems: Sickle cell intrahepatic cholestasis is an uncommon but severe type of liver damage that happens when sickled red cells block blood vessels in the liver. This blockage prevents adequate levels of oxygen from reaching liver tissue. These episodes are usually sudden and may happen more than once. Children often recover, but some adults may have chronic problems that lead to liver failure. Frequent blood transfusions can lead to liver damage from iron overload.
• Priapism: Priapism is an unwanted and sometimes prolonged painful erection. This happens when blood flow out of the erect penis is blocked by sickled cells. Over time, priapism can cause permanent damage to the penis and lead to impotence. Priapism that lasts for more than 4 hours is a medical emergency.
• Stroke or silent brain injury: Silent brain injury, also called silent stroke, is damage to the brain without outward signs of stroke. This injury is common and can be detected on magnetic resonance imaging (MRI) scans. Silent brain injury can lead to difficulty in learning, making decisions, or holding down a job.

Serious anemia complications

People who have sickle cell disease usually also have mild to moderate anemia. At times, however, they can have severe anemia. Severe anemia can be life-threatening.

Severe anemia in a newborn or child who has sickle cell disease may be a result of one of two conditions:

• Aplastic crisis: An aplastic crisis is usually caused by a parvovirus B19 infection, also called fifth disease or slapped cheek syndrome. Parvovirus B19 is a very common infection, but in sickle cell disease, it can cause the bone marrow to stop producing new red cells for a while, leading to severe anemia.
• Splenic sequestration crisis: Your spleen filters your blood and destroys old blood cells. In people who have sickle cell disease, red blood cells may get trapped in the spleen, making it quickly grow larger than normal. With red blood cells trapped in the spleen, fewer are available to circulate in the blood, and this can lead to severe anemia. A large spleen may also cause pain in the left side of the belly. A parent can usually feel a spleen that is larger than normal in a child’s belly.

Aplastic crisis and splenic sequestration crisis most commonly occur in newborns and children who have sickle cell disease. Adults who have sickle cell disease may also experience episodes of severe anemia, but these usually have other causes. Babies and newborns who have severe anemia may not want to eat and may seem very sluggish.

Sickle cell disease can raise your risk of problems during pregnancy. If you are pregnant or planning for pregnancy, meet with a healthcare provider who specializes in high-risk pregnancies and has experience with patients who have sickle cell disease.

Your provider may prescribe certain vitamins and will be careful to prescribe pain medicines that are safe for you and your baby. You should not use hydroxyurea during pregnancy.

You may need to have one or more blood transfusions during pregnancy to treat problems, such as anemia symptoms that get worse. You may also experience more pain crises or be at higher risk of having acute chest syndrome. Your provider will talk to you about how to help prevent these complications.

If you or your child has symptoms of sickle cell disease, your healthcare provider may use a number of tests to diagnose the condition.

Blood test and genetic tests

If you do not know whether you make sickle hemoglobin, you can find out by having your blood tested. You may also have a genetic test performed on your blood. This way, you can learn whether you carry a gene — or have the trait — for sickle hemoglobin that you could pass on to a child.

Genetic testing can help determine which type of sickle cell disease you have or can help confirm a diagnosis if results from blood tests are not clear. Genetic testing can also tell whether you have one or two copies of the sickle hemoglobin gene.

Prenatal screening

Healthcare providers can also diagnose sickle cell disease before a baby is born. This is done using either a sample of amniotic fluid, the liquid in the sac surrounding a growing embryo, or a sample of tissue taken from the placenta, the organ that attaches the umbilical cord to the womb.

Testing before birth can be done as early as 8 to 10 weeks into the pregnancy. This testing looks for the sickle hemoglobin gene rather than the abnormal hemoglobin itself. This testing cannot predict the severity of the disease.

Newborn screening

In newborn screening programs, drops of blood from a heel prick are collected on a special type of paper. The hemoglobin from this blood is then tested in a lab. Newborn screening results are sent to the provider who ordered the test and to your child’s healthcare provider.

Providers from a special follow-up newborn screening team will contact you directly if your child has sickle cell disease. Your child’s providers will then retest your child to make sure the diagnosis is correct.

Newborn screening programs also find out whether your baby has the sickle cell trait and is a carrier. If this is the case, counseling will be offered. Remember that when a child has sickle cell trait or sickle cell disease, their future siblings or your child’s future children may be at risk.

A blood and bone marrow transplant is currently the only cure for some patients who have sickle cell disease. After early diagnosis, your healthcare provider may recommend medicines or transfusions to manage complications, including chronic pain.

Babies who have sickle cell disease may see a hematologist, a doctor who specializes in blood diseases such as sickle cell disease. For newborns, the first sickle cell disease visit should take place before 8 weeks of age.

Medicines

Medicine to prevent the sickling of red blood cells

Voxelotor treats sickle cell disease in adults and children 4 years old and older. The oral medicine prevents red blood cells from forming the sickle shape and binding together. This may reduce the destruction of some red blood cells, which in turn lowers the risk for anemia and improves blood flow to your organs.

Possible side effects include headache, diarrhea, abdominal pain, nausea, fatigue, and fever. Rarely, allergic reactions may occur, causing rashes, hives, or mild shortness of breath. Talk to your healthcare provider about other medicines you take.

Medicine to reduce vaso-occlusive and pain crises

Crizanlizumab-tmca is approved for adults and children 16 years old and older who have sickle cell disease. The medicine, which is given through an intravenous (IV) line in the vein, helps prevent blood cells from sticking to blood vessel walls and causing blood flow blockage, inflammation, and pain crises.

Possible side effects include nausea, joint pain, back pain, and fever.

Medicine to reduce or prevent multiple complications

Hydroxyurea is an oral medicine that has been shown to reduce or prevent several complications of sickle cell disease.

• Use in adults: Many studies of adults with hemoglobin SS or hemoglobin Sβ (sickle cell beta) thalassemia showed that hydroxyurea lowered the number of episodes of pain crises and acute chest syndrome. It also improved anemia and reduced the need for transfusions and hospital admissions.
• Use in children: Studies in children with severe hemoglobin SS or Sβ thalassemia showed that hydroxyurea lowered the number of vaso-occlusive crises and hospitalizations. A study of children between the ages of 9 and 18 months who had hemoglobin SS or Sβ thalassemia also showed that hydroxyurea lowered the number of pain episodes and the incidence of dactylitis (painful swelling of the hands and feet). There is no information about how safe or effective hydroxyurea is in children under 9 months old.
• Pregnancy: Pregnant people should not use hydroxyurea.

Since hydroxyurea can decrease several complications of sickle cell disease, most experts recommend daily use for children and adults with hemoglobin SS or Sβ0 thalassemia who have frequent painful episodes, recurrent chest crises, or severe anemia.

Possible side effects include a lowered white blood cell count or platelet count. Rarely, hydroxyurea can worsen anemia. These side effects usually go away quickly if a patient stops taking the medicine. When the patient restarts it, the healthcare provider usually prescribes a lower dose.

It is still unclear whether hydroxyurea can cause problems later in life in people who have sickle cell disease and take the medicine for many years. Studies suggest that hydroxyurea does not put people at a higher risk of cancer and does not affect growth in children, but further studies are needed.

Medicine to treat pain

The FDA approved L-glutamine for people age 5 and older to lower the number of pain crises. Research showed that patients taking L-glutamine had fewer hospital admissions than patients taking a placebo. The medicine is prescribed as a powder that is mixed into liquids or foods like applesauce or cereal.

Possible side effects include nausea, fatigue, chest pain, and musculoskeletal pain. L-glutamine has not yet been tested in older adults.

Over-the-counter pain medicine, such as acetaminophen or ibuprofen, can be used to treat mild to moderate pain. Stronger or more serious pain may need to be treated in a clinic or hospital. Your provider may prescribe stronger medicines called opioids for severe pain.

Medicine to reduce risk of infection

Penicillin taken twice a day helps lower children's chance of having a serious infection in the bloodstream. Newborns need to take liquid penicillin. Older children can take tablets.

Many healthcare providers will stop prescribing penicillin after a child has reached the age of 5. Some providers prefer to continue to prescribe this antibiotic throughout a person's life, particularly if the person has hemoglobin SS or hemoglobin Sβ0 thalassemia, since people who have sickle cell disease are still at risk. All people who have had surgical removal of the spleen (called a splenectomy) or a past infection with pneumococcus should keep taking penicillin throughout their lives.

Transfusions

Your doctor may recommend transfusion to treat and prevent certain sickle cell disease complications.

These transfusions may include:

• Acute transfusions treat complications that cause severe anemia. Doctors may also use transfusions when a patient has an acute stroke, in many cases of acute chest crises, and in multi-organ failure. A patient who has sickle cell disease usually receives blood transfusions before surgery, to prevent complications.
• Red blood cell transfusions increase the number of red blood cells and provide normal red blood cells that are more flexible than red blood cells with sickle hemoglobin.
• Regular or ongoing blood transfusions may help lower the chances of another stroke in people who have had an acute stroke.

Doctors also recommend blood transfusions for children who have abnormal transcranial Doppler (TCD) ultrasound results, because transfusions can reduce the chance of having a first stroke. Some doctors use this approach to treat complications that do not improve with hydroxyurea. Doctors may also use transfusions in people who have too many side effects from hydroxyurea. Possible complications include alloimmunization, which can make it hard to find a matching unit of blood for a future transfusion; infection; and iron overload.

Your healthcare provider may recommend transfusions to treat and prevent certain sickle cell disease complications. You may have one or more of the following kinds of transfusions.

• Acute transfusions treat complications that cause severe anemia. Providers may also use transfusions for patients in cases of an acute stroke, in many cases of acute chest crises, and in multi-organ failure. A patient who has sickle cell disease usually receives blood transfusions before surgery, to prevent complications.
• Red blood cell transfusions increase the number of red blood cells and also provide normal red blood cells that are more flexible than red blood cells with sickle hemoglobin.
• Regular or ongoing blood transfusions may help lower the chances of another stroke in people who have had an acute stroke.

Healthcare providers also recommend blood transfusions for children who have abnormal transcranial Doppler (TCD) ultrasound results, because transfusions can lower the chance of having a first stroke. Some healthcare providers use this approach to treat complications that do not improve with hydroxyurea. Providers may also use transfusions in people who have too many side effects from hydroxyurea. Possible complications include alloimmunization, which occurs when the transfusion recipient develops antibodies to the blood being transfused, making it hard to find a matching unit of blood for a future transfusion. Infection and iron overload can also occur.

Blood and bone marrow transplant

A blood and bone marrow transplant is currently the only cure for sickle cell disease, but it is not for everyone. Many patients who have sickle cell disease do not have a relative who is a close enough genetic match to be a donor. A well-matched donor is needed for a patient to have the best chance for a successful transplant.

Currently, most transplants to treat sickle cell disease are performed in children who have had complications, such as strokes, acute chest crises, and recurring pain crises. These transplants usually use a matched donor. Blood and bone marrow transplants are riskier in adults.

Several medical centers are looking into new ways to help more people who have sickle cell disease get a transplant. These ways include blood and bone marrow transplant techniques in children and adults who do not have a matched donor in the family or who are older than most recipients.

Blood and bone marrow transplants are successful in about 85% of children when the donor is related and human leukocyte antigen (HLA)–matched. Even with this high success rate, transplants still have risks. Complications can include serious infections, seizures, and other clinical problems. About 5% of people who have received such transplants have died. Sometimes transplanted cells attack the recipient’s organs. This is called graft-versus-host disease. You will get medicine to prevent many of the complications, but they can still happen.

Potential genetic therapy treatments

Researchers at the NHLBI are exploring ways genetic therapies may help provide new treatments or cure for sickle cell disease. Genetic therapies aim to treat or cure conditions by adding new DNA or changing existing DNA.

Genetic therapy involves either restoring a faulty or missing gene or adding a new gene that improves the way the cell works. Researchers take blood or bone marrow from a patient and modify their stem cells in a laboratory using genetic therapies.

Genetic therapies that modify a person’s own hematopoietic stem cells may provide a cure for people who have sickle cell disease and do not have a well-matched donor. Modified stem cells can be injected into the blood; then the cells travel in the bloodstream to the marrow spaces inside the bones. Once inside the bone marrow, the cells can produce healthy red blood cells that do not sickle.

Follow these steps to help relieve symptoms and help you manage your condition at home.

Receive routine follow-up care

• See your healthcare provider regularly. Most people who have sickle cell disease should see their provider every 3 to 12 months, depending on their age.
• Get regular vaccines, including an influenza or flu shot every year, and the COVID-19 vaccine. Your provider may also recommend a second pneumococcus (PPSV23) vaccination, in addition to the pneumococcus (PCV13) vaccination that all children get as part of their regular immunizations. This second vaccine is given after 24 months of age and again 5 years later. Adults who have sickle cell disease and have not received any pneumococcal vaccine should get a dose of the PCV13 vaccine. They should later receive the PPSV23 if they have not already received it or if it has been more than 5 years since they did. Follow these guidelines even if you or your child is still taking penicillin.

Learn what to do in a pain crisis

• When an acute crisis is just starting, drink lots of fluids and take a nonsteroidal anti-inflammatory (NSAID) pain medicine, such as ibuprofen. If you have kidney problems, acetaminophen is often preferred.
• If you cannot manage the pain at home, go to a sickle cell disease day hospital or outpatient unit or an emergency room to receive additional, stronger medicines and IV fluids. You may need to be admitted to the hospital to fully control an acute pain crisis. You may be able to return home once your pain is under better control.

Adopt a healthy lifestyle

Get regular physical activity

Regular physical activity can help manage risk factors for heart disease such as high blood cholesterol, high blood pressure, and overweight and obesity. Before starting any exercise program, ask about what level of physical activity is right for you.

Choose heart-healthy foods

Heart-healthy eating may include the DASH (Dietary Approaches to Stop Hypertension) eating plan. A heart-healthy eating plan includes fruits, vegetables, and whole grains and limits saturated fats, sodium (salt), added sugars, and alcohol.

Quit smoking

For information and support to quit smoking or vaping, visit Smoking and Your Heart, or call the National Cancer Institute's Smoking Quitline at 1-877-44U-QUIT (1-877-448-7848).

Prevent problems over your or your child’s lifetime

• Avoid situations that may set off a crisis. Extreme heat or cold, as well as sudden changes in temperature, are often triggers. When going swimming, ease into the water rather than jumping right in.
• Do not travel in an aircraft cabin that is unpressurized.
• If you experience priapism (a prolonged, painful erection),you may be able to relieve your symptoms by doing light exercise, emptying your bladder by urinating, drinking more fluids, and taking medicine recommended by your healthcare provider.
• If your child attends day care, preschool, or school, speak to their teacher about the disease. Teachers need to know what to watch for and how to accommodate your child.
• Learn how to palpate (feel) your child’s spleen. Because of the risk of splenic sequestration crisis, caretakers should learn how to palpate a child’s spleen. They should try to feel for the spleen daily and more often when the child is ill. If the spleen feels larger than usual, they should call the care provider.
• Take care of your mental health. Talk to your family and friends about how you are feeling. Talk to your provider if you have feelings of depression or anxiety. Supportive counseling and, sometimes, antidepressant medicines may help.