Point mutation in β-globin: glutamate → valine at position 6. Autosomal recessive; ~8–10% of African Americans carry the trait.
Heterozygotes are protected against P falciparum malaria
Newborn screening
Deoxygenated HbS polymerizes → rigid sickle cells.
Promoted by hypoxia, dehydration, acidosis, cold · inhibited by HbF
Symptoms start after ~6 months as HbF falls
Pain crises (bone), dactylitis (first sign in infants), priapism, stroke (children), avascular necrosis of femoral head, renal papillary necrosis.
Sickled cells block small vessels
Transcranial Doppler screening for stroke risk
Acute chest syndrome
leading cause of death
Fever, chest pain, new lung infiltrate, hypoxemia.
Pulmonary vaso-occlusion ± infection or fat embolism
O₂, antibiotics, exchange transfusion
Children: splenic sequestration (sudden pooling → shock). By adolescence: repeated infarcts → autosplenectomy.
Howell-Jolly bodies; encapsulated infections
S pneumoniae, H influenzae, N meningitidis, Salmonella · vaccines + penicillin to age 5
Chronic extravascular + intravascular hemolysis → anemia, jaundice, pigment gallstones; marrow expansion.
Parvovirus B19 → aplastic crisis
Osteomyelitis: Salmonella (also S aureus)
Usually no symptoms. The hypoxic, hypertonic renal medulla still sickles.
Hematuria, isosthenuria, papillary necrosis
Renal medullary carcinoma in young patients
HbC: glutamate → lysine at β6; HbC crystals and target cells; mild hemolysis.
HbSC: milder than SS, but retinopathy and splenomegaly persist
Rod-shaped crystals inside RBCs
Hb electrophoresis; metabisulfite screen.
Hydroxyurea (↑ HbF), transfusion, L-glutamine, crizanlizumab
Stem cell transplant or gene therapy can cure