Sickle Cell Disease

Sickle cell disease is an inherited disease caused by defects, called mutations, in the beta globin gene that helps make hemoglobin. Normally, hemoglobin in red blood cells takes up oxygen in the lungs and carries it through the arteries to all the cells in the tissues of the body. Red blood cells that contain normal hemoglobin are disc shaped and flexible so that they can move easily through large and small blood vessels to deliver oxygen.

Sickle hemoglobin is not like normal hemoglobin. The mutations in the gene cause a problem when oxygen levels in the blood are lower, which occurs once the hemoglobin has delivered oxygen to the cells in the body’s tissues. With less oxygen, the abnormal hemoglobin S gene can cause rigid, non-liquid protein strands to form within the red blood cell. These rigid strands can change the shape of the cell, causing the sickled red blood cell that gives the disease its name.

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 is unable to reach nearby tissues. The lack of oxygen in tissue can cause attacks of sudden, severe pain, called pain crises. These pain attacks can occur without warning, and a person who has them often needs to go to the hospital for effective treatment.

Because sickle cells cannot change shape easily, they 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 normal. This condition, called anemia, can cause a person to have less energy.

When the hemoglobin S gene is inherited from only one parent, and a normal hemoglobin gene—hemoglobin A—is inherited from the other, a person will have sickle cell trait. People with sickle cell trait are generally healthy.

Only rarely do people who have sickle cell trait have complications similar to those seen in people who have sickle cell disease. But people with sickle cell trait are carriers of a defective hemoglobin S gene, so they can pass it on when they have a child.

If the child’s other parent also has sickle cell trait or another abnormal hemoglobin gene, such as thalassemia, hemoglobin C, hemoglobin D, or hemoglobin E, that child has a chance of having 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 percent chance of inheriting two normal hemoglobin A genes. In this case, the child does not have sickle cell trait or disease.
• A 50 percent chance of inheriting one normal hemoglobin A gene and one hemoglobin S gene. This child has sickle cell trait.
• A 25 percent 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 firstborn child has sickle cell disease, there is still a 25 percent 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 he or she carries a sickle hemoglobin gene, a doctor can order a blood test to find out.

• Diagnosis will discuss tests and procedures that your doctor may use to diagnose sickle cell disease for you or your baby.
• Living With will discuss what your doctor may recommend to manage your complications.
• Research for Your Health will discuss how we are using current research and advancing research to treat and cure sickle cell disease.
• Participate in NHLBI Clinical Trials will discuss our open and enrolling clinical studies that are investigating treatment and approaches for sickle cell disease.

If a person has sickle cell disease, 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 require that all newborn babies receive screening for sickle cell disease. When a child has sickle cell disease, parents are notified before the child has symptoms.

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

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

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

Acute pain (sickle cell or vaso-occlusive) crisis

Acute pain episodes, or 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 several places:

• Abdomen
• Arms
• Chest
• Lower back
• Legs

A crisis can be brought on by various conditions:

• High altitudes
• Dehydration, or not drinking enough fluids
• Illness
• Stress
• Temperature changes

But often a person does not know what triggers, or causes, the crisis.

Chronic pain

Many adolescents and adults with sickle cell disease 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.

Severe anemia

People with sickle cell disease 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 sickle cell disease may be a result of events:

• Aplastic crisis. 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.
• Blood cells getting trapped in the spleen. The spleen is an organ that is located in the upper left side of the belly. The 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 enlarge quickly. With red blood cells trapped in the spleen, fewer are available to circulate in the blood, and this can set off severe anemia. A large spleen may also cause pain in the left side of the belly. A parent can usually feel the enlarged spleen in the belly of his or her child.

Splenic sequestration crisis and aplastic crisis most commonly occur in infants 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.

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

• Fatigue
• Dizziness
• Pale skin
• Shortness of breath

Babies and newborns with severe anemia may not want to eat and may seem very sluggish.

Infections

The spleen is important for protection against certain kinds of infections. Sickle cells can damage the spleen and weaken or destroy its function even in young patients.

People who have sickle cell disease who have damaged spleens are at risk for serious bacterial infections in the blood, lung, brain, or bone that can be life-threatening. Some of these bacteria include:

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

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
• Cough
• Fever
• Rapid breathing
• Shortness of breath

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 sickle cell disease, 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:

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

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.

When people who have sickle cell disease show symptoms of stroke, their families or friends should call 9-1-1 right away.

SILENT STROKE AND THINKING PROBLEMS

Brain imaging and tests of thinking, or 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 difficulty in earning, making decisions, or holding down a job.

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.

Heart disease

People who have sickle cell disease can have problems with blood vessels in the heart and with heart function. The heart can become larger than normal. People who have sickle cell disease can also develop pulmonary hypertension.

People who have sickle cell disease and who have received frequent blood transfusions may also have heart damage from iron overload.

Pulmonary hypertension

In adolescents and adults, injury to blood vessels in the lungs can make it hard for the heart to pump blood through those blood vessels. 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.

Kidney problems

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

Sickle cell disease 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. 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 who have sickle cell disease 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 four hours, emergency medical care should be sought to avoid complications.

Gallstones

When red cells undergo hemolysis, 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 sickle cell disease.

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

• Nausea
• Right-side upper belly pain
• 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 sickle cell disease.

Sickle cell intrahepatic cholestasis is an uncommon but severe type 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 who have sickle cell disease 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 who have sickle cell disease 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 who have sickle cell disease 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 who have sickle cell disease can be risky for both the mother and the baby.

Mothers may have medical complications that include:

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

They also are at higher risk for:

• Miscarriages
• Premature births
• Small-for-date or underweight babies

Mental health

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

People who have sickle cell disease may also have trouble coping with pain and fatigue, as well as with frequent medical visits and hospitalizations.

• Treatment will discuss treatment-related complications or side effects.
• Living With will explain ways to manage complications of sickle cell disease.

People who do not know whether they make sickle hemoglobin or another abnormal hemoglobin, such as SC, Sβ thalassemia, and SE, can find out by having their blood tested. This way, they can learn whether they carry a gene—or have the trait—for an abnormal hemoglobin that they could pass on to a child.

When each parent has this information, he or she can be better informed about the chances of having a child with some type of sickle cell disease, such as hemoglobin SS, SC, Sβ thalassemia, or others.

When a child has sickle cell disease, early diagnosis is important to better prevent complications.

Every state in the United States, the District of Columbia, and the U.S. territories require that every baby be tested for sickle cell disease as part of a newborn screening program. In newborn screening programs, blood from a heel prick is collected in “spots” on a special paper. The hemoglobin from this blood is then analyzed in special labs. Newborn screening results are sent to the doctor who ordered the test and to the child’s primary doctor.

If a baby is found to have sickle cell disease, health providers from a special follow-up newborn screening group contact the family directly to make sure that the parents know the results. The child is always retested to be sure that the diagnosis is correct.

Newborn screening programs also find out whether the baby has an abnormal hemoglobin trait. If so, the parents are informed, and counseling is offered. Remember that when a child has sickle cell trait or sickle cell disease, a future sibling or the child’s own future child may be at risk. These possibilities should be discussed with the primary care doctor, a blood specialist called a hematologist, or a genetic counselor.

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

Testing before birth can be done as early as eight to 10 weeks into the pregnancy. This testing looks for the sickle hemoglobin gene rather than the abnormal hemoglobin.

• Return to Signs, Symptoms, and Complications to review early signs and symptoms and complications of sickle cell disease.
• Return to Screening and Prevention to review how to screen for sickle cell disease.

Babies with sickle cell disease may see a hematologist, a doctor with special training in blood diseases such as sickle cell disease. For infants, the first sickle cell disease visit should take place before 8 weeks of age.

If someone was born in a country that does not perform newborn screening, he or she might be diagnosed with sickle cell disease later in childhood. These people should also be referred as soon as possible for special care.

All people who have sickle cell disease should see their health care providers every three to 12 months, depending on the person’s age. Your doctor or medical team can help to prevent problems by taking certain steps:

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

Preventing infection

In sickle cell disease, the spleen does not work properly or at all. This problem makes people who have sickle cell disease more likely to get severe infections.

Penicillin

In children who have sickle cell disease, 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 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 life.

Vaccines

People who have sickle cell disease should receive all recommended childhood vaccines. They should also receive additional vaccines to prevent other infections.

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

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 who has sickle cell disease is maintaining a healthy weight.

Doctors will also track a person’s blood pressure. When a person who has sickle cell disease 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 who have sickle cell disease need to have frequent lab tests.

• Blood tests can tell your doctor whether you have another health problem, such as anemia or 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 results are 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 patient’s eyes every 1 to 2 years from the age of 10 on.

These exams can detect sickle cell disease-related problems of the eye. Regular exams can help doctors find and treat problems early to prevent loss of vision. A patient 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 patient should receive the screening. People who have sickle cell disease and their caretakers should discuss with their doctors whether screening makes sense for them.

Cognitive screening

Patients who have sickle cell disease can develop cognitive 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 who have sickle cell disease should tell their doctors or nurses if they have cognitive problems, such as difficulties learning in school, making decisions, or organizing their thoughts. Patients can be referred for cognitive testing. This testing can identify areas in which a person could use extra help.

Children who have sickle cell disease and who have cognitive problems may qualify for an Individualized Education Program, or IEP. An IEP is a plan that helps students 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 sickle cell disease and their caretakers about complications and also review information at every visit.

Because there are many 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 do not expect people to know everything after one discussion. People who have sickle cell disease and their families should not be afraid to ask questions.

Topics that are usually covered include:

• A plan for what to do and where to get care if a patient has a fever, pain, or other signs of sickle cell disease complications that need immediate attention
• Hours when medical staff are available and contact information to use when people who have sickle cell disease or caretakers have questions
• How sickle cell disease is inherited and the risk of having a child with sickle cell disease
• How to palpate, or 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.
• How to recognize and manage pain
• The importance of regular medical visits, screening tests, and evaluations

Transitioning care

When children who have sickle cell disease 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 who have sickle cell disease 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.

Compared with pediatrics, there are often fewer adult sickle cell disease programs available in a given region. This makes it more difficult for a person who has sickle cell disease to find appropriate doctors, particularly doctors with whom they feel comfortable.

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

Acute pain

Each person who has sickle cell disease should have a home treatment regimen that is best suited to their needs. The providers on the team usually help a patient develop a written, tailored care plan. If possible, the person who has sickle cell disease 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 patient to drink lots of fluids and to take a non-steroidal anti-inflammatory (NSAID) pain medicine, such as ibuprofen. When a person has kidney problems, acetaminophen is often preferred.
• If pain persists, many patients 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 who has sickle cell disease cannot control the pain at home, he or she should go to a sickle cell disease day hospital/outpatient unit or an emergency room to receive additional, stronger medicines and intravenous (IV) fluids.
• Some patients 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.
• Patients 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 with 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 who have sickle cell disease, the cause is often poorly understood. Taking pain medicines daily may help to decrease the pain. Some examples of these medicines include:

• Amitriptyline
• Duloxetine
• Gabapentin
• NSAID drugs, such as ibuprofen
• Strong pain medicines, such as opioids. These should be taken with caution and only under your doctor’s direction because of the risk of addiction or overdose.

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.

Severe anemia

Patients 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 patient will need careful monitoring and treatment in the hospital. A patient also usually needs a blood transfusion. People who have sickle cell disease 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 with 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.

Return to Signs, Symptoms, and Complications to review possible complications from sickle cell disease.

Infections

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

All children and adults who have sickle cell disease and a fever of more than 38.5°C or 101.3°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 outpatients.

Acute chest syndrome

People who have sickle cell disease 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 with 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 who have sickle cell disease and have symptoms of stroke should be brought to the hospital right away by an ambulance. If a patient is having symptoms of stroke, call 9-1-1.

Symptoms of stroke may include:

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

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

Silent stroke and cognitive problems

Children and adults who have sickle cell disease 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 patient may be able to relieve priapism by:

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

If a patient has priapism that lasts for four 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 with 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.

Return to Signs, Symptoms, and Complications to review possible complications from sickle cell disease.

Pregnancy

Pregnant women who have sickle cell disease are at greater risk for problems. They should always see an obstetrician, or OB, who has experience with patients who have sickle cell disease and with high-risk pregnancies and deliveries. The obstetrician should work with a hematologist or primary medical doctor who is well informed about sickle cell disease and its complications.

Pregnant women who have sickle cell disease 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 who has sickle cell disease 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.

Pregnant women should not use hydroxyurea.

Hydroxyurea is an oral medicine that has been shown to reduce or prevent several sickle cell disease complications. This medicine was studied in patients who have sickle cell disease, 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 people who have sickle cell disease, 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 children between the ages of 9 and 18 months with hemoglobin SS or Sβ thalassemia also showed that hydroxyurea decreased the number of pain episodes and dactylitis.

Since hydroxyurea can decrease several complications of sickle cell disease, 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 who have 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 sickle cell disease who have severe, recurrent pain. There is little information available about how effective hydroxyurea is for these types of sickle cell disease.

In all situations, people who have sickle cell disease should discuss with their doctors whether hydroxyurea is an appropriate medicine 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 patient does not take it regularly, it will not work as well or it will not work at all.

A person who has sickle cell disease and 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 patient stops taking the medication. When the patient restarts it, the 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 who have sickle cell disease and 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 sickle cell disease complications. The red blood cells in a transfusion have normal hemoglobin in them.

A blood transfusion helps to increase 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 circulatory system. Red blood cell transfusions decrease the risk for blockages in the blood vessels and improve oxygen delivery to the tissues and organs.

Acute transfusion in sickle cell disease

Doctors use blood transfusions in sickle cell disease for 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.

Chronic transfusion

Doctors recommend regular or ongoing blood transfusions for patients 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 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. 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:

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

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

People who have sickle cell disease and who receive transfusions should be monitored for and immunized against hepatitis. They should also receive regular screenings for iron overload. If a patient 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.

A blood and bone marrow transplant is currently the only cure for some patients who have sickle cell disease. Unfortunately, most patients who have sickle cell disease either are too old for a transplant or do not have a relative who is a good 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.

Who receives blood and bone marrow transplants?

Most sickle cell disease transplants are currently 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 one in 10 children who has sickle cell disease has a matched donor without sickle cell disease in their families, the number of people who get transplants is low.

Blood and bone marrow transplants are is more risky in adults, and that is why most transplants are done in children.

Several medical centers are researching new sickle cell disease 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. Hopefully, more people who have sickle cell disease will be able to receive a transplant in the future using these new methods.

What are the risks?

Blood and bone marrow transplants are successful in about 85 percent of children when the donor is related and HLA matched. Even with this high success rate, transplants still have risks.

Complications can include severe infections, seizures, and other clinical problems. About 5 percent of people who have received such transplants have died. Sometimes transplanted cells attack the recipient’s organs. This is called graft-versus-host disease.

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

• Living With will explain what your doctor may recommend to manage the complications of sickle cell disease.
• Research for Your Health will discuss how we are using current research and advancing research to treat people who have sickle cell disease.
• Participate in NHLBI Clinical Trials will explain our open and enrolling clinical studies that are investigating treatments for sickle cell disease.

Like all people, you and your child should strive to maintain a healthy lifestyle that includes:

• Being physically active. People who have sickle cell disease often tire easily, so be careful to pace yourself and avoid very strenuous activities.
• Getting enough sleep
• Heart-healthy eating, including limiting alcohol. Drink extra water to avoid dehydration.
• Quitting smoking. Visit Smoking and Your Heart and the National Heart, Lung, and Blood Institute’s Your Guide to a Healthy Heart. Although these resources focus on heart health, they include basic information about how to quit smoking. For free help and support to quit smoking, you can call the National Cancer Institute’s Smoking Quitline at 1-877-44U-QUIT (1-877-448-7848).

To prevent and control complications, your doctor may recommend the following:

• Avoid overexertion and dehydration. Take time out to rest and drink plenty of fluids.
• Avoid situations that may set off a crisis. Extreme heat or cold, as well as abrupt 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.
• Take your medicines as your doctor prescribes. Get any medical and lab tests or immunizations that your doctor orders.

See a doctor right away if you have any of the following danger signs:

• Fever
• Problems breathing
• Stroke symptoms
• Sudden loss of vision
• Symptoms of a spleen that is larger than normal
• Symptoms of severe anemia

If your child attends daycare, preschool, or school, speak to his or her teacher about the disease. Teachers need to know what to watch for and how to accommodate your child.

Make and keep regular appointments with your doctor or medical team. These visits will help to reduce the number of acute problems that need immediate care. Your medical team can help prevent complications and improve your quality of life.

Every patient experiences pain differently. Work with your doctor to develop a pain management plan that works for you. This often includes over-the-counter medicines, as well as stronger medicines that you get with a prescription.

You may find other methods that help your pain, such as:

• Using a heating pad
• Taking a warm bath
• Engaging in distracting and relaxing activities, such as listening to music, talking on the phone, or watching TV
• Massage therapy
• Physical therapy
• Acupuncture

Living with sickle cell disease can be very stressful. At times, you may feel sad or depressed. Talk to your doctor or medical team if you or your child is having any emotional problems. Tell your doctor right away if you or your child is feeling very depressed. Some people find counseling or antidepressant medicines helpful.

You may find that speaking to a counselor or psychiatrist or participating in a support group is helpful. When they provide love and support to people who have sickle cell disease, friends and families can help to relieve stress and sadness. Let your loved ones know how you feel and what you need.