ConditionBlood & immune system
Sickle Cell Disease
Sickle cell disease (SCD) is an inherited blood disorder in which red blood cells contain an abnormal hemoglobin (hemoglobin S) that makes them stiff and curved like a sickle. These cells block small blood vessels and break down early, causing episodes of severe pain, anemia, infections, stroke and organ damage. It affects about 100,000 people in the US, mostly of African, Hispanic, Middle Eastern, Mediterranean and South Asian ancestry. Newborn screening, preventive care, hydroxyurea and newer therapies, including gene therapy, have greatly improved outlook.
Also called: SCD, sickle cell anemia (HbSS), sickle cell disorder, hemoglobin SC disease, sickle beta-thalassemia
At a glance
- What it is
- An inherited disorder causing sickle-shaped, fragile red blood cells.
- Inheritance
- Two abnormal hemoglobin genes (at least one sickle gene); carriers have sickle cell trait.
- Main problems
- Pain crises, anemia, infections, acute chest syndrome, stroke, organ damage.
- Prevention
- Newborn screening, penicillin in childhood, vaccines, yearly brain ultrasound in children.
- Treatment
- Pain management, hydroxyurea, transfusions, crizanlizumab, L-glutamine; stem cell transplant and gene therapy can cure.
When to get help
Call 911 or go to the ER
- Fever of 38.3 °C (101 °F) or higher: go to the ER immediately, as infections can become life-threatening within hours
- Chest pain, cough, fast breathing or low oxygen (possible acute chest syndrome)
- Sudden weakness, numbness, facial droop, speech difficulty, severe headache or seizure (possible stroke): call 911 or your local emergency number
- A painful erection lasting more than 2 to 4 hours (priapism)
- A child who is pale, very tired, with a rapidly enlarging spleen or belly (possible splenic sequestration)
See a doctor within a day or two
- Pain not controlled by home pain plan
- New jaundice, dark urine or unusual paleness and tiredness
- Sudden vision changes
Book a routine appointment
- Missed hydroxyurea doses, vaccines, or yearly eye, kidney and (in children) transcranial Doppler checks
- Planning pregnancy
How sickle cell disease works
Hemoglobin carries oxygen in red blood cells. In SCD, hemoglobin S clumps into long rods when it releases oxygen, distorting cells into rigid sickle shapes. Sickled cells:
- block blood vessels, starving tissues of oxygen (vaso-occlusion), causing pain and organ damage
- break apart early, living 10 to 20 days instead of about 120, causing chronic hemolytic anemia and jaundice
- damage blood vessel linings, promoting inflammation and clotting
Types of sickle cell disease
| Type | Genes | Severity |
|---|---|---|
| Sickle cell anemia (HbSS) | Two sickle genes | Usually most severe |
| HbS beta-zero thalassemia | Sickle + beta-zero thalassemia gene | Similar to HbSS |
| HbSC | Sickle + hemoglobin C | Usually milder, but eye and bone problems |
| HbS beta-plus thalassemia | Sickle + beta-plus thalassemia gene | Usually milder |
Sickle cell trait (one sickle gene and one normal gene) is not a disease. Carriers are usually healthy but can pass the gene on. Rarely, trait causes problems with extreme exertion, dehydration or high altitude.
Inheritance
SCD is autosomal recessive. If both parents have sickle cell trait, each child has a:
- 25 percent chance of SCD
- 50 percent chance of sickle cell trait
- 25 percent chance of neither
Symptoms and complications
Pain crises
Sudden, severe pain in the bones, chest, back, arms, legs or abdomen, lasting hours to days. Triggers include dehydration, cold, infection, stress and altitude. See sickle cell crisis.
Other complications
- anemia: fatigue, paleness, shortness of breath
- infections: the spleen is damaged early in life, raising the risk of serious bacterial infections
- acute chest syndrome: chest pain, fever, cough and lung infiltrates; a leading cause of death
- stroke: can occur in children; screening reduces risk
- swelling of hands and feet (dactylitis) in babies
- splenic sequestration: blood pools in the spleen, causing sudden severe anemia in young children
- aplastic crisis: marrow shutdown, often from parvovirus
- priapism
- avascular necrosis of the hip or shoulder
- gallstones from high bilirubin
- kidney damage, leg ulcers, eye damage (retinopathy), pulmonary hypertension
- delayed growth and puberty
- pregnancy complications
Diagnosis
- newborn screening: all US states screen at birth
- hemoglobin electrophoresis or HPLC: identifies the type
- prenatal testing with chorionic villus sampling or amniocentesis
- carrier testing for adults planning a family
Treatment
Preventive care
- penicillin daily from infancy until at least age 5
- vaccines: pneumococcal, meningococcal, Hib, flu and COVID-19
- folic acid
- transcranial Doppler ultrasound yearly from ages 2 to 16 to identify children at high stroke risk
- regular eye, kidney, heart and lung checks
- hydration and avoiding temperature extremes
Disease-modifying medicines
- hydroxyurea: increases fetal hemoglobin, which reduces sickling; lowers pain crises, acute chest syndrome, transfusions and death. Recommended from 9 months of age for HbSS and HbS beta-zero thalassemia
- L-glutamine powder reduces pain crises
- crizanlizumab infusions reduce pain crises in some people
Pain management
- an individualized pain plan for home and the ER
- fluids, warmth and rest
- NSAIDs and opioids as prescribed; rapid treatment in the ER (within an hour of arrival is recommended)
Transfusions
- for severe anemia, acute chest syndrome, stroke and before surgery
- regular transfusions to prevent stroke in high-risk children
- iron chelation to manage iron overload from repeated transfusions
Curative therapies
- bone marrow (stem cell) transplant from a matched donor, mostly in children with severe disease
- gene therapies (approved in the US in 2023) that modify a person's own stem cells to produce healthy or fetal hemoglobin, for people 12 and older with recurrent crises
Outlook
With modern care, most children with SCD in the US now reach adulthood, but life expectancy is still reduced, often into the 40s to 50s on average, and quality of life can be affected by pain and complications. Comprehensive care at a sickle cell center improves outcomes.
Frequently asked questions
What is the difference between sickle cell trait and sickle cell disease?
Sickle cell trait means carrying one sickle gene and one normal gene; people are usually healthy. Sickle cell disease means inheriting two abnormal hemoglobin genes, causing sickling, pain crises, anemia and complications. Two carriers can have a child with the disease.
What triggers a sickle cell crisis?
Common triggers include dehydration, infections, cold temperatures, sudden temperature changes, stress, intense exercise, high altitude and low oxygen. Many crises happen without an obvious trigger.
Can sickle cell disease be cured?
A bone marrow transplant from a matched donor can cure it, mainly in children. Gene therapies approved in 2023 can effectively cure symptoms for some people 12 and older. These treatments carry risks and are not right for everyone.
Why is fever dangerous in sickle cell disease?
The spleen does not work well in SCD, so bacterial infections can spread quickly and become life-threatening within hours. A fever of 38.3 °C (101 °F) or higher needs emergency evaluation and antibiotics.
How does hydroxyurea help sickle cell disease?
Hydroxyurea boosts production of fetal hemoglobin, which does not sickle. This reduces pain crises, acute chest syndrome, hospital stays and transfusions, and improves survival. It is recommended for most children and adults with the severe forms.
Sources
This guide was written from current patient and clinical guidance, including:
- National Heart, Lung, and Blood Institute: Sickle Cell Disease
- CDC: About Sickle Cell Disease
- American Society of Hematology: Guidelines for Sickle Cell Disease
- NHLBI: Evidence-Based Management of Sickle Cell Disease Expert Panel Report
- MedlinePlus: Sickle cell disease