Conditions · Metabolism: heme, bilirubin and iron
Sickle cell disease !
An inherited hemoglobin disease in which red cells bend into a sickle shape, block vessels and cause pain, anemia and organ damage.
Updated 2026-11-01
Structures involved
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- Spleen
- Kidneys
- Gallbladder
- Femoral head cartilage
- Femur
- Right lower lobe
- Left lower lobe
- Middle cerebral artery
In biochemistry
- Glycated haemoglobin (HbA1c)
- Newborn screening
- Chromatography
- Lactate dehydrogenase (LDH) as a lab marker
- Heme oxygenase
- Iron metabolism
- Hemoglobin variants (HbA, HbA2, HbF, HbS, HbC)
- Types of mutations
- Gene therapy
- CRISPR-Cas9 and genome editing
- Protein structure and folding
- Oxygen binding: haemoglobin versus myoglobin
In immunology
- Spleen: white pulp, red pulp, asplenia
- Transfusion reactions
- Secondary immunodeficiency: HIV, malnutrition, drugs, asplenia
In histology
- Blood cells on a smear: erythrocytes, leukocytes, platelets
- Lymph node and spleen under the microscope
In the clinical exam
In physiology
Why it happens
- Pigments in tissue: lipofuscin, hemosiderin, melanin, bilirubin, carbon
- Mendelian inheritance: autosomal dominant, recessive and X-linked
- Hypercoagulable states: inherited and acquired
- Infarction: red vs white, and what decides the damage
- Causes of cell injury
What it is
A group of hemoglobinopathies with HbS (β6 Glu→Val): HbSS (sickle cell anemia), HbSC and HbS/β-thalassemia. Autosomal recessive inheritance.
Who gets it
It is the most common severe hemoglobinopathy in the world, especially in sub-Saharan Africa. In Colombia the trait and the disease are more common in Afro-descendant communities of the Pacific and Caribbean coasts.
Causes
- Two abnormal HBB alleles, at least one carrying HbS
Risk factors
- Both parents carriers (1-in-4 risk per pregnancy)
- Crisis triggers: dehydration, cold, infection, hypoxia, altitude, extreme exercise
Pathophysiology
When deoxygenated, HbS polymerises into fibres that deform and stiffen the red cell. Sickled cells are destroyed (hemolysis, 10–20-day lifespan) and stick to the endothelium with leucocytes and platelets, blocking the microcirculation: ischaemia, pain and infarcts. Hemolysis releases hemoglobin that consumes nitric oxide and harms vessels. Repeated infarcts shrink the spleen (autosplenectomy).
Classification
- HbSS: the most severe form
- HbS/β⁰-thalassemia: similar to HbSS
- HbSC and HbS/β⁺-thalassemia: milder
- Trait (HbAS): carrier, almost always without symptoms
Symptoms and signs
- Crises of severe pain in bones, chest or abdomen
- Painful swelling of hands and feet in infants (dactylitis)
- Pallor, fatigue and jaundice
- Frequent infections
- Delayed growth and puberty
- Prolonged painful erection (priapism)
Diagnosis
- Clinical
- Chronic hemolytic anemia with pain crises in someone with a family history; ideally detected by newborn screening.
- Tests
- Hemoglobin electrophoresis, HPLC or isoelectric focusing (predominant HbS, no HbA in HbSS); blood count with high reticulocytes; smear with sickle cells and Howell-Jolly bodies; high indirect bilirubin and LDH; genetic testing.
- Imaging
- Annual transcranial Doppler from age 2 to 16 to detect stroke risk; chest X-ray in acute chest syndrome; hip MRI for avascular necrosis; ultrasound for gallstones.
Treatment
- Acute
- Pain crisis: prompt analgesia (including opioids), hydration and oxygen if hypoxaemic
- Medical
- Hydroxyurea, which raises HbF and reduces crises, acute chest syndrome and transfusions
- Medical
- Prophylactic penicillin in childhood and full vaccination, including pneumococcal
- Procedure
- Simple or exchange transfusion in stroke, severe acute chest syndrome and primary stroke prevention
- Procedure
- Hematopoietic stem cell transplantation, curative in selected cases; gene therapies are new options
- Follow-up
- Monitoring iron in transfused patients, kidney function, retina and echocardiography
Drugs for this condition
Complications
- Childhood stroke
- Acute chest syndrome and pulmonary hypertension
- Functional asplenia and severe infections; Salmonella osteomyelitis
- Avascular necrosis of the femoral head
- Renal papillary necrosis and chronic kidney disease
- Pigment gallstones
- Leg ulcers and retinopathy
Prognosis
With newborn screening, prophylaxis and hydroxyurea most children reach adulthood, although life expectancy remains reduced.
Prevention
- Newborn screening and genetic counselling for carrier couples
Test yourself
Think of the answer, then tap the question to see it.
Which mutation produces HbS?
Glutamic acid replaced by valine at position 6 of β-globin (HBB gene).
Why do people with sickle cell anemia get more pneumococcal infections?
Repeated infarcts destroy the spleen (autosplenectomy), removing defence against encapsulated bacteria.
Which study is used in children to prevent stroke?
Transcranial Doppler: high velocities indicate risk and lead to regular transfusions.
Why is sickle cell trait common in malaria regions?
Carriers are protected against severe P. falciparum malaria.
Related conditions
- Thalassemias (α and β)
- Neonatal jaundice
- Gallstones (cholelithiasis)
- Malaria
- Ischaemic stroke
- Avascular necrosis of the femoral head
- Chronic kidney disease
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Sickle cell disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Sickle cell disease: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); HBB gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Sickle Cell Disease | Sickle Cell Anemia | MedlinePlus (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.
