Sickle Cell

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

Hemoglobin	Components
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 (β^Sβ^S). 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

References

1. Clancy, S. (n.d.). Genetic Mutation. Retrieved January 19, 2021, from https://www.nature.com/scitable/topicpage/genetic-mutation-441/
2. Sundd, P., Gladwin, M., & Novelli, E. (2019, January 24). Pathophysiology of Sickle Cell Disease. Retrieved January 19, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053558/
3. Cober, M., & Phelps, S. (2010, July). Penicillin prophylaxis in children with sickle cell disease. Retrieved January 19, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018247/
4. RJ;, A. (n.d.). TCD in sickle cell disease: An important and useful test. Retrieved January 19, 2021, from https://pubmed.ncbi.nlm.nih.gov/15703904/
5. Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014. (2014). Pediatrics, 134(6). doi:10.1542/peds.2014-2986