Hemoglobin Patterns in Sickle Cell Disease
No, hemoglobin A (HbA) and hemoglobin S (HbS) are NOT both elevated in classic sickle cell disease (HbSS genotype)—patients with HbSS have predominantly or exclusively HbS with little to no HbA present. 1, 2
Hemoglobin Electrophoresis Patterns by Genotype
The hemoglobin composition varies dramatically depending on the specific sickle cell genotype:
HbSS (Sickle Cell Anemia - Most Severe Form)
- HbS comprises 80-100% of total hemoglobin 1, 3
- HbA is absent or nearly absent (0-10%) 1
- HbF levels are typically less than 1-3% 1
- This represents the classic and most severe form of sickle cell disease 4
Sickle Cell Trait (HbAS - Carrier State)
- HbA levels are 55-65% 1
- HbS levels are 30-40% 1
- This is a benign carrier state, not sickle cell disease 1
Sickle Beta-Plus Thalassemia (HbS/β+ Thal)
- HbS levels are 70-80% 1
- HbA levels are reduced to 10-25% 1
- HbA2 is elevated above 3-5% 1
- This represents a mild-to-moderate clinical phenotype of actual sickle cell disease requiring disease-specific management 1
Sickle Beta-Zero Thalassemia (HbS/β⁰ Thal)
- No HbA is present 1
- HbS levels are 80-90% 1
- HbF levels are 5-15% 1
- This creates a severe clinical phenotype resembling HbSS disease 1
Critical Clinical Distinction
The presence or absence of HbA is the key distinguishing feature between different sickle cell genotypes and determines disease severity. 1, 4
- Patients with HbSS have essentially no functional HbA production due to homozygous inheritance of the sickle mutation 2, 3
- The pathophysiology stems from HbS polymerization at low oxygen tension, causing red cell rigidity and vaso-occlusion 5, 6
- Baseline hemoglobin levels in severe sickle cell disease are chronically low at 60-90 g/L (6-9 g/dL), which represents their steady state 7, 5
Common Pitfall to Avoid
Do not confuse sickle cell trait (carrier state with both HbA and HbS present) with sickle cell disease (HbSS genotype with predominantly HbS). 1 Only the trait has substantial amounts of both hemoglobins; the disease state has predominantly or exclusively HbS.