Sickle Cell

Hemoglobin’s molecular core consists of 2 alpha subunits and 2 beta subunits

Fetal Hemoglobin (Hemoglobin F)α2βγβγ
Adult Hemoglobin (Hemoglobin A)α2βAβA
Alternative Adult Hemoglobin (Hemoglobin A2)α2𝛅2
Sickle Cell Trait (typically asymptomatic)α2βAβS
Sickle Cell Disease (Hemoglobin S)α2βSβS

Sickle Cell Disease arises from a mutation of both genetic copies of the DNA coding for β-subunits (βSβS). This mutation causes valine to be substituted for glutamic acid at the sixth amino acid (1). When in a deoxygenated state, these Hemoglobin S molecules aggregate and change the shape of the erythrocyte, leading to “sickling”, which in turn increases likelihood of vaso-occlusion (2).

Outpatient Management

  • Hydration
  • Avoid temperature extremes or stress
  • Tylenol/NSAIDs/opioids for pain
  • Vaccinations (because of splenic infarcts)
    • S. pneumoniae
    • N. meningitidis
    • H. influenzae
    • HBV
    • Influenza
  • Prophylactic penicillin initiated within 3 months of life, continued until 5 years old (3)
  • Hydroxyurea in all patients (this takes months to take effect)
  • Supplement folic acid, multivitamin, Vitamin D, and calcium
  • Routine retinal evaluations
  • Transcranial doppler (TCD) starting at 2 years old and repeated every 6-12 months to identify individuals higher at risk for stroke who may benefit from regular blood transfusions (4)
  • Hematopoietic stem cell transplantation is curative, but carries its own risks and morbidities (5)

Inpatient Management

  • Sickle crises arise from de-oxygenated hemoglobin causing erythrocyte “sickling” and leading to a vaso-occlusion.
  • Many different crises are possible, including splenic sequestration, stroke, renal failure, priapism, and bone infarct. As a general rule, management includes hydration, pain control, and blood transfusions. We’ll focus on Acute Chest Syndrome, as this is a frequent question on board exams.
    • Acute Chest Syndrome (5)
      • Subjective: Chest pain, fever, cough, shortness of breath
      • Objective: Fever, tachypnea, hypoxemia
      • Differential Diagnosis includes pneumonia, pulmonary embolism, ACS
      • Treatment: Empiric antibiotics (Cephalosporin and macrolide), pain control (generally IV), hydration, and incentive spirometry.
        • Blood transfusion if hgb is > 1.0 g/dL below baseline
        • Exchange transfusion if disease progressing to point where oxygen saturations not able to be maintained > 90% on supplemental oxygen, or if the patient is in significant respiratory distress


  1. Clancy, S. (n.d.). Genetic Mutation. Retrieved January 19, 2021, from
  2. Sundd, P., Gladwin, M., & Novelli, E. (2019, January 24). Pathophysiology of Sickle Cell Disease. Retrieved January 19, 2021, from
  3. Cober, M., & Phelps, S. (2010, July). Penicillin prophylaxis in children with sickle cell disease. Retrieved January 19, 2021, from
  4. RJ;, A. (n.d.). TCD in sickle cell disease: An important and useful test. Retrieved January 19, 2021, from
  5. Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014. (2014). Pediatrics, 134(6). doi:10.1542/peds.2014-2986

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