Sickle Cell Anemia

What causes sickle cell anemia

Hemoglobin is the protein in red blood cells that carries oxygen. In sickle cell anemia, a change in the HBB gene produces hemoglobin S. When oxygen levels are low, hemoglobin S molecules stick together, forming rods that bend red blood cells into a sickle shape. These cells:

• are stiff and sticky, blocking small blood vessels (vaso-occlusion)
• break down in about 10 to 20 days instead of the normal 120, causing hemolytic anemia

Inheritance

Sickle cell anemia is autosomal recessive:

• inheriting two sickle genes (HbSS) causes sickle cell anemia, the most common and often most severe form
• inheriting one sickle gene and a different abnormal gene causes other forms of sickle cell disease, such as HbSC or sickle beta-thalassemia
• inheriting one sickle gene and one normal gene causes sickle cell trait, usually without symptoms

If both parents have sickle cell trait, each child has a 1 in 4 chance of sickle cell anemia.

Symptoms and complications

Symptoms usually start around 5 to 6 months of age, when protective fetal hemoglobin declines.

Pain crises

Sickle cell crises are sudden episodes of severe pain, most often in the back, chest, arms, legs and belly, caused by blocked blood flow. They can last hours to days. Triggers include cold, dehydration, infection, stress, altitude and intense exercise. Some people also have chronic daily pain.

Anemia

Tiredness, paleness, shortness of breath and jaundice (yellow eyes) from rapid red cell breakdown.

Infections

The spleen is damaged early in life, so children are at high risk of serious bacterial infections such as pneumococcal sepsis and meningitis.

Other complications

• hand-foot syndrome (dactylitis): painful swelling of hands and feet, often the first sign in infants
• acute chest syndrome: chest pain, fever, cough and low oxygen. A leading cause of death
• stroke: can occur in childhood. Screening identifies children at risk
• splenic sequestration: blood pools suddenly in the spleen, causing severe anemia
• aplastic crisis: the bone marrow temporarily stops making red cells, often after parvovirus infection
• priapism: painful, prolonged erections
• avascular necrosis of the hip or shoulder
• gallstones
• leg ulcers
• eye damage (retinopathy)
• kidney disease and pulmonary hypertension
• delayed growth and puberty

Diagnosis

• newborn screening: all US states test babies at birth
• hemoglobin electrophoresis or similar tests confirm the type
• genetic testing for prenatal diagnosis
• carrier testing for people planning a family

Treatment

Preventive care

• penicillin daily from about 2 months to at least age 5 to prevent pneumococcal infections
• vaccinations, including pneumococcal, meningococcal and yearly flu vaccines
• transcranial Doppler ultrasound yearly in children aged 2 to 16 to detect stroke risk
• folic acid supplements in some people
• regular checks of eyes, kidneys, lungs and heart

Disease-modifying medicines

• hydroxyurea: increases fetal hemoglobin, reducing pain crises, acute chest syndrome and transfusions, and improving survival. Recommended from 9 months of age for HbSS
• L-glutamine powder: reduces pain crises in some people
• other targeted medicines are available or in development. Ask your hematologist about current options

Blood transfusions

Used for severe anemia, acute chest syndrome, stroke prevention and before surgery. Regular transfusions can cause iron overload, treated with iron chelation medicines.

Curative treatments

• stem cell (bone marrow) transplant: can cure sickle cell disease, most successfully in children with a matched sibling donor
• gene therapies: approved in the US for people aged 12 and older with severe disease. These use the person's own modified stem cells and require high-dose chemotherapy

Managing pain

• a personal pain plan agreed with your care team
• fluids, rest and warmth for mild episodes
• acetaminophen (paracetamol) and NSAIDs at the label dose if your doctor agrees
• prompt opioid pain relief in the emergency department for severe crises
• prompt treatment of fever and infection

Living with sickle cell anemia

• drink plenty of fluids
• avoid extreme cold, high altitude and dehydration
• moderate exercise with rest breaks
• keep vaccinations up to date
• seek care quickly for fever or warning signs
• school and work plans for absences and access to water and bathroom breaks
• psychological support for chronic pain and stigma

Outlook

Thanks to newborn screening, penicillin, vaccines and hydroxyurea, most children with sickle cell anemia in the US now survive to adulthood. Life expectancy is still shorter than average, but it is improving, and curative treatments are becoming more available.

Frequently asked questions

What is the difference between sickle cell anemia and sickle cell trait?

Sickle cell anemia means inheriting two sickle genes, causing disease with pain crises, anemia and complications. Sickle cell trait means inheriting one sickle gene and one normal gene. People with trait usually have no symptoms but can pass the gene to their children.

What triggers a sickle cell crisis?

Common triggers include dehydration, cold temperatures, infections, stress, high altitude, intense exercise and low oxygen. Drinking plenty of fluids, keeping warm and treating infections early help prevent crises.

Can sickle cell anemia be cured?

Yes, in some people. A stem cell transplant from a matched donor can cure it, and gene therapies are now approved for people 12 and older with severe disease. These treatments carry significant risks, so they are not right for everyone.

What is the life expectancy with sickle cell anemia?

With modern care, most people in the US live well into adulthood, though average life expectancy remains lower than in the general population. Preventive care, hydroxyurea and prompt treatment of complications continue to improve survival.