Sickle cell anemia (sickle cell disease)

July 30, 2026

 

Sickle cell anemia (sickle cell disease)



Sickle cell anemia is an autosomal recessive genetic disorder caused by a mutation in the β-globin (HBB) gene. The mutation produces hemoglobin S (HbS), which polymerizes under low oxygen conditions, causing red blood cells to become sickle-shaped.

Definition

  • Inherited hemoglobin disorder affecting the structure of hemoglobin.

  • Characterized by chronic hemolytic anemia and episodes of vaso-occlusion.

Genetic basis

  • Gene: HBB (β-globin gene)

  • Chromosome: 11p15.5

  • Inheritance: Autosomal recessive

  • Mutation: Missense mutation in the sixth codon of the β-globin gene.

The mutation changes glutamic acid to valine at position 6 of the β-globin chain.

Genetics

Inheritance

Autosomal recessive

Gene

HBB

Chromosome

11p15.5

Hemoglobin

HbS

Mutation

Glu → Val at β6

Pathophysiology

  • Deoxygenated HbS molecules polymerize.

  • Red blood cells become rigid and sickle-shaped.

  • Sickled cells obstruct small blood vessels.

  • Repeated sickling damages the red cell membrane.

  • Increased hemolysis causes chronic anemia.

Clinical features

Anemia

  • Fatigue

  • Pallor

  • Jaundice

  • Delayed growth in children

Vaso-occlusive crisis

  • Severe bone pain

  • Chest pain

  • Abdominal pain

  • Hand-foot syndrome (dactylitis)

Complications

  • Acute chest syndrome

  • Stroke

  • Splenic sequestration

  • Functional asplenia

  • Recurrent infections

  • Avascular necrosis

  • Leg ulcers

  • Gallstones

Diagnosis

  • Peripheral blood smear: sickled red cells

  • Sickling test: positive

  • Hemoglobin electrophoresis: confirms HbS

  • High-performance liquid chromatography (HPLC): quantifies HbS

  • Genetic testing: detects HBB mutation

Hemoglobin electrophoresis

Condition

Hb pattern

Normal (AA)

HbA predominant

Sickle trait (AS)

HbA and HbS

Sickle cell anemia (SS)

HbS predominant; HbA absent

Treatment

Supportive care

  • Hydration

  • Analgesics for pain crises

  • Folic acid supplementation

  • Vaccination and infection prevention

Disease-modifying therapy

  • Hydroxyurea (increases fetal hemoglobin, HbF)

  • L-glutamine

  • Crizanlizumab

  • Voxelotor

Curative therapy

  • Hematopoietic stem cell transplantation (selected patients)

  • Gene therapy (emerging treatment)

Prevention

  • Genetic counseling

  • Carrier screening

  • Prenatal diagnosis in high-risk families

Important examination points

  • Inheritance: Autosomal recessive

  • Gene involved: HBB

  • Mutation: Glutamic acid → valine (β6)

  • Abnormal hemoglobin: HbS

  • Major complications: Vaso-occlusive crisis and hemolytic anemia

  • Drug commonly asked in exams: Hydroxyurea

Mnemonic

“SICKLE”

  • Sickled RBCs

  • Inherited (autosomal recessive)

  • Chronic hemolysis

  • Kidney and spleen complications

  • Low oxygen triggers sickling

  • Electrophoresis confirms HbS

References

  1. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. The Lancet. 2010;376(9757):2018-2031.

  2. Kato GJ, Piel FB, Reid CD, et al. Sickle cell disease. Nature Reviews Disease Primers. 2018;4:18010.

  3. Stuart MJ, Nagel RL. Sickle-cell disease. The Lancet. 2004;364(9442):1343-1360.

  4. Nelson DL, Cox MM. Lehninger Principles of Biochemistry. 8th ed. W.H. Freeman.

  5. Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Elsevier.