Sickle Cell Disease

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

Cells in tissues need a steady supply of oxygen to work well. Normally, hemoglobin in red blood cells takes up oxygen in the lungs and carries it to all the tissues of the body.

Red blood cells that contain normal hemoglobin are disc shaped (like a doughnut without a hole). This shape allows the cells to be flexible so that they can move through large and small blood vessels to deliver oxygen.

Sickle hemoglobin is not like normal hemoglobin. It can form stiff rods within the red cell, changing it into a crescent, or sickle shape.

Sickle-shaped cells are not flexible and can stick to vessel walls, causing a blockage that slows or stops the flow of blood. When this happens, oxygen can’t reach nearby tissues.

Normal Red Cells and Sickle Red Cells

Figure A shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin. Figure B shows abnormal, sickled red blood cells blocking blood flow in a blood vessel. The inset image shows a cross-section of a sickle cell with abnormal (sickle) hemoglobin forming abnormal stiff rods.

The lack of tissue oxygen can cause attacks of sudden, severe pain, called pain crises. These pain attacks can occur without warning, and a person often needs to go to the hospital for effective treatment.

Most children with SCD are pain free between painful crises, but adolescents and adults may also suffer with chronic ongoing pain.

The red cell sickling and poor oxygen delivery can also cause organ damage. Over a lifetime, SCD can harm a person’s spleen, brain, eyes, lungs, liver, heart, kidneys, penis, joints, bones, or skin.

Sickle cells can’t change shape easily, so they tend to burst apart or hemolyze. 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 SCD 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 normal. This condition, called anemia, can make a person have less energy.

Sickle cell disease is a life-long illness. The severity of the disease varies widely from person to person.

In high-income countries like the United States, the life expectancy of a person with SCD is now about 40–60 years. In 1973, the average lifespan of a person with SCD in the United States was only 14 years. Advances in the diagnosis and care of SCD have made this improvement possible.

At the present time, hematopoietic stem cell transplantation (HSCT) is the only cure for SCD. Unfortunately, most people with SCD are either too old for a transplant or don’t have a relative who is a good enough genetic match for them to act as a donor. A well-matched donor is needed to have the best chance for a successful transplant.

There are effective treatments that can reduce symptoms and prolong life. Early diagnosis and regular medical care to prevent complications also contribute to improved well-being.

If a person has sickle cell disease (SCD), it is present at birth. But most infants do not have any problems from the disease until they are about 5 or 6 months of age. Every state in the United States, the District of Columbia, and the U.S. territories requires that all newborn babies receive screening for SCD. When a child has SCD, parents are notified before the child has symptoms.

Some children with SCD will start to have problems early on, and some later. Early symptoms of SCD may include:

• Painful swelling of the hands and feet, known as dactylitis
• Fatigue or fussiness from anemia
• A yellowish color of the skin, known as jaundice, or whites of the eyes, known as icteris, that occurs when a large number of red cells hemolyze

The signs and symptoms of SCD will vary from person to person and can change over time. Most of the signs and symptoms of SCD are related to complications of the disease.

Acute Pain (Sickle Cell or Vaso-occlusive) Crisis

Pain episodes (crises) can occur without warning when sickle cells block blood flow and decrease oxygen delivery. People describe this pain as sharp, intense, stabbing, or throbbing. Severe crises can be even more uncomfortable than post-surgical pain or childbirth.

Pain can strike almost anywhere in the body and in more than one spot at a time. But the pain often occurs in the

• Lower back
• Legs
• Arms
• Abdomen
• Chest

A crisis can be brought on by

• Illness
• Temperature changes
• Stress
• Dehydration (not drinking enough)
• Being at high altitudes

But often a person does not know what triggers, or causes, the crisis. (See acute pain management.)

Chronic Pain

Many adolescents and adults with SCD suffer from chronic pain. This kind of pain has been hard for people to describe, but it is usually different from crisis pain or the pain that results from organ damage.

Chronic pain can be severe and can make life difficult. Its cause is not well understood. (See chronic pain management.)

Severe Anemia

People with SCD usually have mild to moderate anemia. At times, however, they can have severe anemia. Severe anemia can be life threatening. Severe anemia in an infant or child with SCD may be caused by:

• Splenic sequestration crisis. The spleen is an organ that is located in the upper left side of the belly. The spleen filters germs in the blood, breaks up blood cells, and makes a kind of white blood cell. A splenic sequestration crisis occurs when red blood cells get stuck in the spleen, making it enlarge quickly. Since the red blood cells are trapped in the spleen, there are fewer cells to circulate in the blood. This causes severe anemia.
  
  A big spleen may also cause pain in the left side of the belly. A parent can usually palpate or feel the enlarged spleen in the belly of his or her child.
• Aplastic crisis. This 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 SCD it can cause the bone marrow to stop producing new red cells for a while, leading to severe anemia.

Splenic sequestration crisis and aplastic crisis most commonly occur in infants and children with SCD. Adults with SCD may also experience episodes of severe anemia, but these usually have other causes.

No matter the cause, severe anemia may lead to symptoms that include:

• Shortness of breath
• Being very tired
• Feeling dizzy
• Having pale skin

Babies and infants with severe anemia may feed poorly and seem very sluggish. (See anemia management.)

Infections

The spleen is important for protection against certain kinds of germs. Sickle cells can damage the spleen and weaken or destroy its function early in life.

People with SCD who have damaged spleens are at risk for serious bacterial infections that can be life-threatening. Some of these bacteria include:

• Pneumococcus
• Hemophilus influenza type B
• Meningococcus
• Salmonella
• Staphylococcus
• Chlamydia
• Mycoplasma pneumoniae

Bacteria can cause:

• Blood infection (septicemia)
• Lung infection (pneumonia)
• Infection of the covering of the brain and spinal cord (meningitis)
• Bone infection (osteomyelitis)

(See how to prevent infections and infection management.)

Acute Chest Syndrome

Sickling in blood vessels of the lungs can deprive a person’s lungs of oxygen. When this happens, areas of lung tissue are damaged and cannot exchange oxygen properly. This condition is known as acute chest syndrome. In acute chest syndrome, at least one segment of the lung is damaged.

This condition is very serious and should be treated right away at a hospital.

Acute chest syndrome often starts a few days after a painful crisis begins. A lung infection may accompany acute chest syndrome.

Symptoms may include:

• Chest pain
• Fever
• Shortness of breath
• Rapid breathing
• Cough

(See acute chest syndrome management.)

Brain Complications

Clinical Stroke

A stroke occurs when blood flow is blocked to a part of the brain. When this happens, brain cells can be damaged or can die. In SCD, a clinical stroke means that a person shows outward signs that something is wrong. The symptoms depend upon what part of the brain is affected. Symptoms of stroke may include:

• Weakness of an arm or leg on one side of the body
• Trouble speaking, walking, or understanding
• Loss of balance
• Severe headache

As many as 24 percent of people with hemoglobin SS and 10 percent of people with hemoglobin SC may suffer a clinical stroke by age 45.

In children, clinical stroke occurs most commonly between the ages of 2 and 9, but recent prevention strategies have lowered the risk. (See Transcranial Doppler (TCD) Ultrasound Screening and Red Blood Cell Transfusions.)

When people with SCD show symptoms of stroke, their families or friends should call 9-1-1 right away. (See clinical stroke management.)

Silent Stroke and Thinking Problems

Brain imaging and tests of thinking (cognitive studies) have shown that children and adults with hemoglobin SS and hemoglobin Sβ0 thalassemia often have signs of silent brain injury, also called silent stroke. Silent brain injury is damage to the brain without showing outward signs of stroke.

This injury is common. Silent brain injury can lead to learning problems or trouble making decisions or holding down a job. (See Cognitive Screening and silent stroke management.)

Eye Problems

Sickle cell disease can injure blood vessels in the eye.

The most common site of damage is the retina, where blood vessels can overgrow, get blocked, or bleed. The retina is the light-sensitive layer of tissue that lines the inside of the eye and sends visual messages through the optic nerve to the brain.

Detachment of the retina can occur. When the retina detaches, it is lifted or pulled from its normal position. These problems can cause visual impairment or loss. (See Eye Examinations.)

Heart Disease

People with SCD can have problems with blood vessels in the heart and with heart function. The heart can become enlarged. People can also develop pulmonary hypertension.

People with SCD who have received frequent blood transfusions may also have heart damage from iron overload. (See transfusion management.)

Pulmonary Hypertension

In adolescents and adults, injury to blood vessels in the lungs can make it hard for the heart to pump blood through them.  This causes the pressure in lung blood vessels to rise. High pressure in these blood vessels is called pulmonary hypertension. Symptoms may include shortness of breath and fatigue.

When this condition is severe, it has been associated with a higher risk of death. (See screening for pulmonary hypertension.)

Kidney Problems

The kidneys are sensitive to the effects of red blood cell sickling.

SCD causes 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 have bedwetting or uncontrolled urination during the night (nocturnal enuresis). This often starts in childhood. Other problems may include:

• Blood in the urine
• Decreased kidney function
• Kidney disease
• Protein loss in the urine

Priapism

Males with SCD can have unwanted, sometimes prolonged, painful erections. This condition is called priapism.

Priapism happens when blood flow out of the erect penis is blocked by sickled cells. If it goes on for a long period of time, priapism can cause permanent damage to the penis and lead to impotence.

If priapism lasts for more than 4 hours, emergency medical care should be sought to avoid complications. (See priapism management.)

Gallstones

When red cells hemolyze, they release hemoglobin. Hemoglobin gets broken down into a substance called bilirubin.  Bilirubin can form stones that get stuck in the gallbladder. The gallbladder is a small, sac-shaped organ beneath the liver that helps with digestion. Gallstones are a common problem in SCD.

Gallstones may be formed early on but may not produce symptoms for years. When symptoms develop, they may include:

• Right-sided upper belly pain
• Nausea
• Vomiting

If problems continue or recur, a person may need surgery to remove the gallbladder.

Liver Complications

There are a number of ways in which the liver may be injured in SCD.

Sickle cell intrahepatic cholestasis is an uncommon, but severe, form of liver damage that occurs when sickled red cells block blood vessels in the liver. This blockage prevents enough oxygen from reaching liver tissue.

These episodes are usually sudden and may recur. Children often recover, but some adults may have chronic problems that lead to liver failure.

People with SCD who have received frequent blood transfusions may develop liver damage from iron overload.

Leg Ulcers

Sickle cell ulcers are sores that usually start small and then get larger and larger.

The number of ulcers can vary from one to many. Some ulcers will heal quickly, but others may not heal and may last for long periods of time. Some ulcers come back after healing.

People with SCD usually don’t get ulcers until after the age of 10.

Joint Complications

Sickling in the bones of the hip and, less commonly, the shoulder joints, knees, and ankles, can decrease oxygen flow and result in severe damage. This damage is a condition called avascular or aseptic necrosis. This disease is usually found in adolescents and adults.

Symptoms include pain and problems with walking and joint movement. A person may need pain medicines, surgery, or joint replacement if symptoms persist.

Delayed Growth and Puberty

Children with SCD may grow and develop more slowly than their peers because of anemia. They will reach full sexual maturity, but this may be delayed.

Pregnancy

Pregnancies in women with SCD can be risky for both the mother and the baby.

Mothers may have medical complications including:

• Infections
• Blood clots
• High blood pressure
• Increased pain episodes

They are also at higher risk for:

• Miscarriages
• Premature births
• “Small-for-dates babies” or underweight babies

(See pregnancy management.)

Mental Health

As in other chronic diseases, people with SCD may feel sad and frustrated at times. The limitations that SCD can impose on a person’s daily activities may cause them to feel isolated from others. Sometimes they become depressed.

People with SCD may also have trouble coping with pain and fatigue, as well as with frequent medical visits and hospitalizations. (See living with emotional issues.)

Babies with sickle cell disease (SCD) should be referred to a doctor or provider group that has experience taking care of people with this disease. The doctor might be a hematologist (a doctor with special training in blood diseases) or an experienced general pediatrician, internist, or family practitioner.

For infants, the first SCD visit should take place before 8 weeks of age.

If someone was born in a country that doesn’t perform newborn SCD screening, he or she might be diagnosed with SCD later in childhood. These people should also be referred as soon as possible for special SCD care.

All people who have SCD should see their SCD care providers regularly. Regularly means every 3 to 12 months, depending on the person’s age. The SCD doctor or team can help to prevent problems by:

• Examining the person
• Giving medicines and immunizations
• Performing tests
• Educating families about the disease and what to watch out for

Preventing Infection

In SCD, the spleen doesn’t work properly or doesn’t work at all. This problem makes people with SCD more likely to get severe infections.

Penicillin

In children with SCD, taking penicillin two times a day has been shown to reduce the chance of having a severe infection caused by the pneumococcus bacteria. Infants need to take liquid penicillin. Older children can take tablets.

Many doctors will stop prescribing penicillin after a child has reached the age of 5. Some prefer to continue this antibiotic throughout life, particularly if a person has hemoglobin SS or hemoglobin Sβ0 thalassemia, since people with SCD 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 life.

Immunizations

People with SCD should receive all recommended childhood vaccines. They should also receive additional vaccines to prevent other infections.

• Pneumococcus. Even though all children routinely receive the vaccine against pneumococcus (PCV13), children with SCD should also receive a second kind of vaccine against pneumococcus (PPSV23). This second vaccine is given after 24 months of age and again 5 years later. Adults with SCD who 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 it has been more than 5 years since they did. A person should follow these guidelines even if he or she is still taking penicillin.
• Influenza. All people with SCD should receive an influenza shot every year at the start of flu season. This should begin at 6 months of age. Only the inactivated vaccine, which comes as a shot, should be used in people with SCD.
• Meningococcus. A child with SCD should receive this vaccine (Menactra or Menveo) at 2, 4, 6, and 12–15 months of age. The child should receive a booster vaccine 3 years after this series of shots, then every 5 years after that.

Height, Weight, Blood Pressure, and Oxygen Saturation

Doctors will monitor height and weight to be sure that a child is growing properly and that a person with SCD is maintaining a healthy weight.

Doctors will also track a person’s blood pressure. When a person with SCD has high blood pressure, it needs to be treated promptly because it can increase the risk of stroke.

Oxygen saturation testing provides information about how much oxygen the blood is carrying.

Blood and Urine Testing

People with SCD need to have frequent lab tests.

Blood tests help to establish a person’s “baseline” for problems like anemia. Blood testing also helps to show whether a person has organ damage, so that it can be treated early.

Urine testing can help to detect early kidney problems or infections.

Transcranial Doppler (TCD) Ultrasound Screening

Children who have hemoglobin SS or hemoglobin Sβ0 thalassemia and are between the ages of 2 and 16 should have TCD testing once a year.

This study can find out whether a child is at higher risk for stroke. When the test is abnormal, regular blood transfusions can decrease the chances of having a stroke.

The child is awake during the TCD exam. The test does not hurt at all. The TCD machine uses sound waves to measure blood flow like the ultrasound machine used to examine pregnant women.

Eye Examinations

An eye doctor, or ophthalmologist, should examine a person’s eyes every 1—2 years from the age of 10 onwards.

These exams can detect if there are SCD-related problems of the eye. Regular exams can help doctors find and treat problems early to prevent loss of vision. A person should see his or her doctor right away for any sudden change in vision.

Pulmonary Hypertension

Doctors have different approaches to screening for pulmonary hypertension. This is because studies have not given clear information as to when and how a person should receive the screening. People with SCD and their caretakers should discuss with their doctor whether screening makes sense for them.

Cognitive Screening

People with sickle cell disease can develop cognitive (thinking) problems that may be hard to notice early in life.

Sometimes these problems are caused by “silent” strokes that can only be seen with magnetic resonance imaging (MRI) of the brain.

People with SCD should tell their doctors or nurses if they have thinking problems, such as difficulties learning in school, slowed decision making, or trouble organizing their thoughts.

People can be referred for cognitive testing. This testing can identify areas in which a person could use extra help.

Children with SCD who have thinking problems may qualify for an Individualized Education Program, or IEP. An IEP is a plan that helps students to reach their educational goals. Adults may be able to enroll in vocational rehabilitation programs that can help them with job training.

Education and Guidance

Doctors and other providers will talk with people who have SCD and their caretakers about complications and also review information at every visit.

Because there are a lot of things to discuss, new topics are often introduced as a child or adult reaches an age when that subject is important to know about.

Doctors and nurses know that there is a lot of information to learn, and they don’t expect people to know everything after one discussion. People with SCD and their families should not be afraid to ask questions.

Topics that are usually covered include:

• Hours that medical staff are available and contact information to use when people with SCD or caretakers have questions
• A plan for what to do and where to get care if a person has a fever, pain, or other signs of SCD complications that need immediate attention
• How SCD is inherited and the risk of having a child with SCD
• The importance of regular medical visits, screening tests, and evaluations
• How to recognize and manage pain
• How to palpate (feel) a 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 frequently when the child is ill. If they feel that the spleen is bigger than usual, they should call the care provider.       

Transitioning Care

When children with SCD become adolescents or young adults, they often need to transition from a pediatric care team to an adult care team. This period has been shown to be associated with increased hospital admissions and medical problems. There seem to be many reasons for this.

Some of the increased risk is directly related to the disease. As people with SCD get older, they often develop more organ damage and more disabilities.

The shift in care usually occurs at the same time that adolescents are undergoing many changes in their emotional, social, and academic lives. The transition to more independent self-management may be difficult, and following treatment plans may become less likely.

When compared with pediatrics, there are often fewer adult SCD programs available in a given region. This makes it more difficult for a person with SCD to find appropriate doctors, particularly those with whom they feel comfortable.

To improve use of regular medical care by people with SCD and to reduce age-related complications, many SCD teams have developed special programs that the make transition easier. Such programs should involve the pediatric and the adult care teams. They should also start early and continue over several years.

Acute Pain

Each person with SCD should have a home treatment regimen that is best suited to their needs. The providers on the SCD team usually help a person develop a written, tailored care plan. If possible, the person with SCD should carry this plan with them when they go to the emergency room.

When an acute crisis is just starting, most doctors will advise the person to drink lots of fluids and to take a non-steroidal anti-inflammatory (NSAID) pain medication, such as ibuprofen. When a person has kidney problems, acetaminophen is often preferred.

If pain persists, many people will find that they need a stronger medicine.

Combining additional interventions, such as massage, relaxation methods, or a heating pad, may also help.

If a person with SCD cannot control the pain at home, he or she should go to an SCD day hospital/outpatient unit or an emergency room to receive additional, stronger medicines and intravenous (IV) fluids.

Some people may be able to return home once their pain is under better control. In this case, the doctor may prescribe additional pain medicines for a short course of therapy.

People often need to be admitted to the hospital to fully control an acute pain crisis.

When taken daily, hydroxyurea has been found to decrease the number and severity of pain episodes.

Some patients may have fewer visits to the hospital or hospitalizations due to severe pain, and may have shorter hospital stays for pain crises if they are taking L-glutamine oral powder (Endari) compared to patients who are not taking this medicine. More research is needed to understand how effective L-glutamine oral powder is as a treatment and which patients may benefit from using it.

Chronic Pain

Sometimes chronic pain results from a complication, such as a leg ulcer or aseptic necrosis of the hip. In this case, doctors try to treat the complication causing the pain.

While chronic pain is common in adults with SCD, the cause is often poorly understood. Taking pain medicines daily may help to decrease the pain. Some examples of these medicines include:

• NSAID drugs, such as ibuprofen
• Duloxetine
• Gabapentin
• Amitriptyline
• Strong pain medicines, such as opiates

Other approaches, such as massage, heat, or acupuncture may be helpful in some cases. Chronic pain often comes with feelings of depression and anxiety. Supportive counseling and, sometimes, antidepressant medicines may help. (See coping and emotional issues.)

Severe Anemia

People should see their doctors or go to a hospital right away if they develop anemia symptoms from a splenic sequestration crisis or an aplastic crisis. These conditions can be life-threatening, and the person will need careful monitoring and treatment in the hospital. A person also usually needs a blood transfusion.

People with SCD and symptoms of severe anemia from other causes should also see a doctor right away.

Some patients may have fewer hospital visits due to sickle cell crises, including splenic sequestration, if they are taking L-glutamine oral powder compared to patients who are not taking this medicine. More research is needed to understand how effective L-glutamine oral powder is as a treatment and which patients may benefit from using it.

Infections

Fever is a medical emergency in SCD. All caretakers of infants and children with SCD should take their child to their doctor or go to a hospital right away when their child has a fever. Adults with SCD should also seek care for fever or other signs of infection.

All children and adults who have SCD and a fever (over 38.50 C or 101.30 F) must be seen by a doctor and treated with antibiotics right away.

Some people will need to be hospitalized, while others may receive care and follow-up as an outpatient.

Acute Chest Syndrome

People with SCD and symptoms of acute chest syndrome should see their doctor or go to a hospital right away.

They will need to be admitted to the hospital where they should receive antibiotics and close monitoring. They may need oxygen therapy and a blood transfusion.

When taken daily, the medicine hydroxyurea has been found to decrease the number and severity of acute chest events.

Some patients may have fewer hospital visits due to sickle cell crises, including acute chest syndrome, if they are taking L-glutamine oral powder compared to patients who are not taking this medicine. More research is needed to understand how effective L-glutamine oral powder is as a treatment and which patients may benefit from using it. 

Clinical Stroke

People with SCD who have symptoms of stroke should be brought to the hospital right away by an ambulance. If a person is having symptoms of stroke, someone should call 9-1-1.

Symptoms of stroke may include:

• Weakness of an arm or leg on one side of the body
• Trouble speaking, walking, or understanding
• Loss of balance
• Severe headache

If imaging studies reveal that the person has had an acute stroke, he or she may need an exchange transfusion. This procedure involves slowly removing an amount of the person’s blood and replacing it with blood from a donor who does not have SCD or sickle cell trait. Afterward, the person may need to receive monthly transfusions or other treatments to help to prevent another stroke.

Silent Stroke and Cognitive Problems

Children and adults with SCD and cognitive problems may be able to get useful help based upon the results of their testing. For instance, children may qualify for an IEP. Adults may be able to enroll in vocational, or job, training programs.

Priapism

Sometimes, a person may be able to relieve priapism by:

• Emptying the bladder by urinating
• Taking medicine
• Increasing fluid intake
• Doing light exercise

If a person has an episode that lasts for 4 hours or more, he should go to the hospital to see a hematologist and urologist.

Some patients may have fewer hospital visits due to sickle cell crises, including priapism, if they are taking L-glutamine oral powder compared to patients who are not taking this medicine. More research is needed to understand how effective L-glutamine oral powder is as a treatment and which patients may benefit from using it.

Pregnancy

Pregnant women with SCD are at greater risk for problems. They should always see an obstetrician, or OB, who has experience with SCD and high-risk pregnancies and deliveries.

The obstetrician should work with a hematologist or primary medical doctor who is well informed about SCD and its complications.

Pregnant women with SCD need more frequent medical visits so that their doctors can follow them closely. The doctor may prescribe certain vitamins and will be careful to prescribe pain medicines that are safe for the baby.

A pregnant woman with SCD may need to have one or more blood transfusions during her pregnancy to treat complications, such as worsening anemia or an increased number of pain or acute chest syndrome events.

What Is Hydroxyurea?

Hydroxyurea is an oral medicine that has been shown to reduce or prevent several SCD complications.

This medicine was studied in patients with SCD because it was known to increase the amount of fetal hemoglobin (hemoglobin F) in the blood. Increased hemoglobin F provides some protection against the effects of hemoglobin S.

Hydroxyurea was later found to have several other benefits for a person with SCD, such as decreasing inflammation.

• Use in adults. Many studies of adults with hemoglobin SS or hemoglobin Sβ thalassemia showed that hydroxyurea reduced the number of episodes of pain crises and acute chest syndrome. It also improved anemia and decreased the need for transfusions and hospital admissions.
• Use in children. Studies in children with severe hemoglobin SS or Sβ thalassemia showed that hydroxyurea reduced the number of vaso-occlusive crises and hospitalizations. A study of very young children (between the ages of 9 and 18 months) with hemoglobin SS or hemoglobin Sβ thalassemia also showed that hydroxyurea decreased the number of episodes of pain and dactylitis.

Who Should Use Hydroxyurea?

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

Some experts offer hydroxyurea to all infants over 9 months of age and young children with hemoglobin SS or Sβ0 thalassemia, even if they do not have severe clinical problems, to prevent or reduce the chance of complications. There is no information about how safe or effective hydroxyurea is in children under 9 months of age.

Some experts will prescribe hydroxyurea to people with other types of SCD who have severe, recurrent pain. There is little information available about how effective hydroxyurea is for these types of SCD.

In all situations, people with SCD should discuss with their doctors whether or not hydroxyurea is an appropriate medication for them.

Pregnant women should not use hydroxyurea.

How Is Hydroxyurea Taken?

To work properly, hydroxyurea should be taken by mouth daily at the prescribed dose. When a person does not take it regularly, it will not work as well, or it won’t work at all.

A person with SCD who is taking hydroxyurea needs careful monitoring. This is particularly true in the early weeks of taking the medicine. Monitoring includes regular blood testing and dose adjustments.

What Are the Risks of Hydroxyurea?

Hydroxyurea can cause the blood’s white cell count or platelet count to drop. In rare cases, it can worsen anemia. These side effects usually go away quickly if a person stops taking the medication. When a person restarts it, a doctor usually prescribes a lower dose.

Other short-term side effects are less common.

It is still unclear whether hydroxyurea can cause problems later in life in people with SCD who take it for many years. Studies so far suggest that it does not put people at a higher risk of cancer and does not affect growth in children. But further studies are needed.

Red Blood Cell Transfusions

Doctors may use acute and chronic red blood cell transfusions to treat and prevent certain SCD complications. The red blood cells in a transfusion have normal hemoglobin in them.

A transfusion helps to raise the number of red blood cells and provides normal red blood cells that are more flexible than red blood cells with sickle hemoglobin. These cells live longer in the circulation. Red blood cell transfusions decrease vaso-occlusion (blockage in the blood vessel) and improve oxygen delivery to the tissues and organs.

Acute Transfusion in SCD

Doctors use blood transfusions in SCD for complications that cause severe anemia. They may also use them when a person has an acute stroke, in many cases of acute chest crises, and in multi-organ failure.

A person with SCD usually receives blood transfusions before surgery to prevent SCD-related complications afterwards.

Chronic Transfusion

Doctors recommend regular or ongoing blood transfusions for people who have had an acute stroke, since transfusions decrease the chances of having another stroke.

Doctors also recommend chronic blood transfusions for children who have abnormal 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. They may also use transfusions in people who have too many side effects from hydroxyurea.

What Are the Risks of Transfusion Therapy?

Possible complications include:

• Hemolysis
• Iron overload, particularly in people receiving chronic transfusions (can severely impair heart and lung function)
• Infection
• Alloimmunization (can make it hard to find a matching unit of blood for a future transfusion)

All blood banks and hospital personnel have adopted practices to reduce the risk of transfusion problems.

People with SCD who receive transfusions should be monitored for and immunized against hepatitis. They should also receive regular screenings for iron overload. If a person has iron overload, the doctor will give chelation therapy, a medicine to reduce the amount of iron in the body and the problems that iron overload causes.

Hematopoietic Stem Cell Transplantation

At the present time, hematopoietic stem cell transplantation (HSCT) is the only cure for SCD. People with SCD and their families should ask their doctor about this procedure.

What Are Stem Cells?

Stem cells are special cells that can divide over and over again. After they divide, these cells can go on to become blood red cells, white cells, or platelets.

A person with SCD has stem cells that make red blood cells that can sickle. People without SCD have stem cells that make red cells that usually won’t sickle.

What Stem Cells Are Used in HSCT?

In HSCT, stem cells are taken from the bone marrow or blood of a person who does not have sickle cell disease (the donor). The donor, however, may have sickle cell trait.

The donor is often the person’s sister or brother. This is because the safest and most successful transplants use stem cells that are matched for special proteins called HLA antigens. Since these antigens are inherited from parents, a sister or brother is the most likely person to have the same antigens as the person with SCD.

What Happens During HSCT?

First, stem cells are taken from the donor. After this, the person with SCD (the recipient) is treated with drugs that destroy or reduce his or her own bone marrow stem cells.

The donor stem cells are then injected into the person’s vein. The injected cells will make a home in the recipient’s bone marrow, gradually replacing the recipient’s cells. The new stem cells will make red cells that do not sickle.

Which People Receive HSCT?

At the present time, most SCD transplants 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.

Because only about 1 in 10 children with SCD has a matched donor without SCD in their families, the number of people with SCD who get transplants is low.

HSCT is more risky in adults, and that is why most transplants are done in children.

There are several medical centers that are researching new SCD HSCT techniques in children and adults who don’t have a matched donor in the family or are older than most recipients. Hopefully, more people with SCD will be able to receive a transplant in the future, using these new methods.

What Are the Risks?

HSCT is successful in about 85 percent of children when the donor is related and HLA matched. Even with this high success rate, HSCT still has risks.

Complications can include severe infections, seizures, and other clinical problems. About 5 percent of people have died.  Sometimes transplanted cells attack the recipient’s organs (graft versus host disease).

Medicines are given to prevent many of the complications, but they still can happen.

Learn about some of the ways we continue to translate current research into improved health for people with sickle cell disease.

• Evidence-Based Management of Sickle Cell Disease: 2014 Expert Panel Report. We supported a review and analysis of the latest sickle cell disease research and the creation of this summary report. This report offers guidance to health care professionals on how best to care for their patients with sickle cell disease. Explore the Expert Panel Report materials and talk to your doctor about this report.
• NHLBI-funded Registry and Surveillance System for Hemoglobinopathies (RuSH) project. In 2010, we partnered with the Centers for Disease Control (CDC) and Prevention and funded its RuSH project. This project is studying how many people have sickle cell disease and thalassemia in parts of the United States. RuSH will inform future national disease and health status monitoring strategies, as well as the targeted delivery of health education materials. Visit CDC RuSH for more information.
• NHLBI-funded Transfusions Changing to Hydroxyurea (TWiTCH) study. Our TWiTCH study found that hydroxyurea is as effective as blood transfusions at reducing transcranial Doppler (TCD) blood velocities in children with sickle cell disease. High TCD blood velocities are a risk factor for stroke in children with sickle cell disease. Read a NIH press release about the TWiTCH study findings.
• NIH-wide translational research support for next generation sickle cell disease treatments. We supported trans-NIH efforts leading to the development of a promising new sickle cell disease treatment called Aes-103, which may reduce pain caused by sickle cell disease. Read a NIH press release to learn more about the development of Aes-103.
• Sickle Cell Disease Forum 2015. We sponsored this forum to bring together the sickle cell disease community—patients and their families, advocates, health care professionals, researchers, community and professional organizations, policymakers, government agencies, industry, and the media—to help chart the future of sickle cell disease research. Read the Sickle Cell Disease Forum Engaging the Community: Developing Solutions for a summary of discussions from this two-day event. Explore other resources from this forum.
• Sickle Cell in Focus Conference 2016. We co-sponsored this international event to bring together researchers and health professionals to discuss new advances and challenges for sickle cell disease clinical care. Explore resources from this conference.
• Annual Sickle Cell Disease Clinical Research Meetings. Each year, we bring together researchers and health professionals to discuss clinical trials, research and clinical care for sickle cell disease. Explore resources from the 2016 annual meeting.
• Global leadership in sickle cell disease research and care. We are proud to serve as a global leader and respond to legislative calls to increase U.S. global health efforts. The NHLBI Global Health Strategic Plan seeks to stimulate global health research, education and training for many conditions, including sickle cell disease in sub-Saharan Africa and Southeast Asia, where disease burden is high. Also, we are collaborating with other NIH Institutes and Centers in Human Heredity and Health in Africa (H3Africa) projects.

Learn about some of the pioneering research contributions we have made over the years that have improved clinical care and increased the life expectancy for people with sickle cell disease.

In support of our mission, we are committed to advancing sickle cell disease research in part through the following ways.

• We perform research. Our Division of Intramural Research, which includes investigators in our Sickle Cell Branch and Sickle Cell Program, is actively engaged in sickle cell disease research. In support of a Department of Health and Human Services sickle cell program, our Sickle Cell Branch leads a government-wide collaboration to rapidly move new discoveries into treatments for patients.
• We fund research. The research we fund today will help improve our future health. Our Division of Blood Diseases and Resources (DBDR) oversees the sickle cell disease research we fund, as well as the external clinical research centers. The Research centers funded by our Excellence in Hemoglobinopathies Research Award (EHRA) program are helping us understand, measure, and treat pain; non-invasively assess blood flow; prevent stroke or blood clots in the lungs; manage disease complications; and see if modifying how genes are expressed can be used to treat sickle cell disease. Search the NIH Research Portfolio Online Reporting Tools (RePORT) to learn about research NHLBI is funding on sickle cell disease.
• We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) Program now includes participants with sickle cell disease, which may help us understand how genes contribute to differences in disease severity and how patients respond to treatment. The NHLBI Strategic Vision highlights ways we may support research over the next decade, including new efforts for sickle cell disease.

Participate in NHLBI Clinical Trials will discuss some of our sickle cell disease clinical trials. It also includes studies that look at how to improve stem cell transplants for adults with sickle cell disease and how genes and other factors contribute to pain crises in sickle cell disease.