What do the hemoglobin electrophoresis patterns FA, FAS, and FS represent?

Hemoglobin Electrophoresis Patterns: FA, FAS, and FS

Pattern Definitions

These hemoglobin electrophoresis patterns represent different combinations of hemoglobin types present in blood, listed in order of quantity from highest to lowest. 1

FA Pattern

• FA indicates the presence of fetal hemoglobin (F) as the predominant type, followed by adult hemoglobin (A) 1
• This pattern is normal in newborns and young infants during the physiological transition from fetal to adult hemoglobin production 1
• In older children and adults, persistent FA pattern may indicate hereditary persistence of fetal hemoglobin (HPFH), a benign condition 2
• The FA pattern can also be seen in beta-thalassemia trait where elevated HbF persists beyond infancy 2

FAS Pattern

• FAS represents fetal hemoglobin (F) predominating, followed by hemoglobin S (sickle hemoglobin), then hemoglobin A 1, 3
• This pattern is diagnostic of sickle cell trait (HbAS) in a newborn detected through neonatal screening 1, 4
• The "F" appears first because newborns normally have high fetal hemoglobin levels that gradually decline over the first 6-12 months of life 1
• By mid-childhood, the pattern evolves to AS (hemoglobin A greater than S), confirming sickle cell trait rather than sickle cell disease 1
• FAS pattern can be reliably identified using high-performance liquid chromatography (HPLC) even from dried blood spot specimens stored at room temperature for up to 6 weeks 3

FS Pattern

• FS indicates fetal hemoglobin (F) predominating with hemoglobin S, but NO hemoglobin A present 1
• This pattern is diagnostic of homozygous sickle cell disease (HbSS) in a newborn 1, 4
• The absence of hemoglobin A distinguishes this from sickle cell trait 1
• By mid-childhood, as fetal hemoglobin declines, the pattern becomes predominantly S (hemoglobin S only) with decreased or trace amounts of HbF 1
• The FS pattern can also represent sickle-beta-zero thalassemia (HbS/β⁰-thalassemia), which is clinically indistinguishable from HbSS in newborns but shows decreased MCV (mean corpuscular volume) in later childhood 1

Clinical Significance of Hybrid Hemoglobins

• The asymmetric hemoglobin hybrid FS (α₂γβˢ) forms in patients with sickle cell disease and inhibits hemoglobin S polymerization, which is the molecular basis for the protective effect of fetal hemoglobin in sickle cell disease 5
• Higher levels of fetal hemoglobin correlate with milder clinical course and reduced sickling complications in patients with HbSS 5
• Mass spectrometry can detect these hybrid tetramers, with ratios of HbFS to HbS correlating closely (r² = 0.96) with physiological predictions 5

Diagnostic Pitfalls

• G-gamma-beta⁺-HPFH with concurrent HbS can mimic HbS/β⁺-thalassemia on routine electrophoresis, showing elevated HbS, HbF, and HbA 2
• The key distinguishing feature is normocytic red blood cells in HPFH versus microcytosis in beta-thalassemia 2
• HPLC analysis showing predominantly G-gamma chains in the fetal hemoglobin fraction confirms HPFH, which has a benign clinical course unlike HbS/β⁺-thalassemia 2
• Newborn screening results must be confirmed with repeat testing after 6-9 months of age when the hemoglobin pattern stabilizes and beta-chain variants become fully expressed 1