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 (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
- Acute Chest Syndrome (5)
References
- Clancy, S. (n.d.). Genetic Mutation. Retrieved January 19, 2021, from https://www.nature.com/scitable/topicpage/genetic-mutation-441/
- 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/
- 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/
- 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/
- Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014. (2014). Pediatrics, 134(6). doi:10.1542/peds.2014-2986
