A 10-year-old girl comes to the office for a routine follow-up visit. The girl has a history of sickle cell disease and had frequent admissions for pain crises in early childhood. Two years ago, she was started on hydroxyurea, which eliminated the pain crises. She has had no recent illnesses, emergency department visits, or hospitalizations. Vital signs are normal, and examination is unremarkable. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 9.0 g/L |
| Mean corpuscular volume | 105 μm3 |
| Reticulocytes | 2.0% |
| Platelets | 212,000/mm3 |
| Leukocytes | 5,000/mm3 |
| Neutrophils | 22% |
| Eosinophils | 3% |
| Lymphocytes | 67% |
| Monocytes | 8% |
Which of the following hemoglobin patterns would most likely be seen on electrophoresis in this patient?
Electrophoresis patterns in sickle cell syndromes | |||||
HbA | HbA2 | HbF | HbS | HbC | |
Normal | ++++ | + | + | None | None |
Sickle cell trait | +++ | + | + | +++ | None |
Sickle cell anemia (SCA) | None | + | + | ++++ | None |
SCA on hydroxyurea | None | + | ++ | +++ | None |
Hemoglobin SC disease | None | + | + | +++ | +++ |
All functioning hemoglobin contains a pair of alpha globulins and a pair of non-alpha globulins. The non-alpha globulin differentiates the hemoglobin type and determines the physiologic properties of the molecule in different conditions (eg, pH, temperature, 2,3-bisphosphoglycerate level). In healthy children and adults:
The predominant hemoglobin is hemoglobin A (HbA) (alpha and beta globulins).
Small quantities (1%-2%) of other hemoglobin are also present, including hemoglobin A2 (alpha and delta globulins) and hemoglobin F (HbF) (alpha and gamma globulins).
Sickle cell disease (SCD) is marked by an absence of normal beta globulin due to mutations in both beta globulin genes. The sickle mutation generates a new type of hemoglobin, hemoglobin S (HbS), which polymerizes when deoxygenated. This leads to reduced erythrocyte deformability and increased erythrocyte fragility, causing painful vasooclusion, organ ischemia, and chronic hemolysis.
Because patients with SCD are unable to generate normal beta globulin, they cannot produce HbA; therefore, HbA will be undetectable on electrophoresis (Choices C, E, F). Other forms of hemoglobin that do not contain beta globulin (eg, HbA2, HbF) are usually present at normal or mildly increased levels.
Because HbF prevents HbS from polymerizing, hydroxyurea, which increase HbF levels, is often administered to reduce SCD complications. Patients who respond to hydroxyurea (as in this patient with reduced symptoms) usually have 10%-30% HbF on electrophoresis. Side effects of therapy include macrocytosis and myelosuppression.
(Choice A) Patients with sickle cell anemia (heterozygous sickle cell disease) who are not on hydroxyurea predominantly have HbS with normal or mildly increased HbF. Hydroxyurea significantly increases HbF production.
(Choice D) Hemoglobin SC disease is marked by the sickle mutation in one beta globulin and a different point mutation in the other beta globulin (lysine for glutamine at position 6). This leads to 2 predominant hemoglobin types: HbS and HbC. Treatment with hydroxyurea is also helpful in this condition and would cause elevated (not normal) HbF levels.
Educational objective:
Sickle cell disease is marked by mutations in both beta globulins with at least one beta globulin having the sickle mutation. This generates a new type of hemoglobin called HbS, which polymerizes when deoxygenated. Treatment with hydroxyurea increases Hemoglobin F, which prevents HbS polymerization and reduces symptoms.