Sickle cell disease
Sickle cell disease is an autosomal recessive hemoglobinopathy caused by a beta-globin point mutation that produces hemoglobin S, which polymerizes under deoxygenation to sickle erythrocytes and drive chronic hemolysis and vaso-occlusion. Diagnosis is confirmed by hemoglobin electrophoresis or HPLC showing predominant HbS, and lifelong management centers on hydroxyurea, folic acid, penicillin prophylaxis and vaccination for functional asplenia, transcranial Doppler stroke screening, and, in severe disease, transfusion, hematopoietic stem cell transplant, or gene therapy.
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What this article covers
- Overview
Definition: sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy from homozygosity (or compound heterozygosity) for hemoglobin S, an abnormal beta-globin that polymerizes under…
- Epidemiology
Predominantly affects patients of African descent: in the United States sickle hemoglobin is far more common among Black persons, with sickle cell trait present in roughly 8% of Black Americans.
- Risk factors
Family history and ancestry from a historically malaria-endemic region: SCD requires inheritance of a sickle allele from both parents.
- Pathophysiology
The causal mutation: a point mutation in the beta-globin gene substitutes valine for glutamate at position 6, producing hemoglobin S.
- Clinical features
Chronic hemolytic anemia: pallor, fatigue, jaundice, and scleral icterus from ongoing hemolysis, present from early childhood in Hb SS disease.
- Differential diagnosis
Hereditary spherocytosis: hemolytic anemia with jaundice and splenomegaly, but spherocytes rather than sickle cells, a positive osmotic fragility/EMA-binding test, and a negative Coombs test.
- Diagnosis
Confirm with hemoglobin electrophoresis or HPLC: the diagnostic test, showing a predominant hemoglobin S band.
- Management
Confirm the genotype and establish baseline care: hemoglobin electrophoresis, baseline CBC, reticulocyte count, hemolysis labs, and enrollment in a comprehensive sickle cell program.
- Complications
Acute chest syndrome: the leading cause of death in SCD, from vaso-occlusion in the pulmonary vasculature; covered in detail in sickle cell disease complications.
- Prognosis
Survival has improved dramatically with newborn screening, prophylaxis, and hydroxyurea, with many patients now living into middle adulthood or beyond, though median survival remains reduced.
- Prevention
Universal folic acid 1 mg PO once daily in all patients to prevent folate-deficient megaloblastic change on top of chronic hemolysis.
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