The normal Hemoglobin molecule (HbA) consists of a Heme (iron-containing) moiety plus 2 pairs of polypeptide Globin Chains, alpha (α) and beta (β). Other types of normal globins not found in Hb A are gamma (γ) and delta (δ) chains.
Hemoglobin A (HbA) Molecule
Or More Simplyα-globin chain + α-globin chain Heme + β-globin chain + β-globin chain
Adult RBCs contain >97% Hb A. The rest consists of ≤2.5% Hb A2 composed of 2 α-chains + 2 δ-chains, and perhaps ≤1% fetal Hb, or Hb F, which is composed of 2 α-chains + 2 γ-chains.
β-Thalassemia Minor involves decreased quantities of β-chains. So Hb A comprises only ≤95% of RBC hemoglobin. There’s more heme moiety around, so α-chains join with δ-chains and γ-chains. Percentages of Hb A2 and Hb F are increased.
But suppose there’s co-existing iron deficiency (less heme). The α-chains will bind preferentially with available β-chains, there’ll be extra α-chains left over, BUT there won’t be that much Heme moiety to form Hb A2 and Hb F.
- So the relative proportions of Hb A, Hb A2, and Hb F will seem deceptively normal
- Hemoglobin Electrophoresis measures percentages, not quantities
Replace the iron deficiency, there’ll be more heme moieties, the deficient β-chains won’t be enough to match with all the alphas. More Hb A2 and Hb F will be formed and incorporated into RBCs. Then the electrophoretic pattern will reveal the diagnosis (decreased Hb A, increased Hb A2 and Hb F).
MORAL – With microcytic anemia, always check a ferritin and transferrin saturation percent [or zinc protoporphyrin] for iron deficiency before ordering hemoglobin electrophoresis.
[if this might be easier to grasp by looking at sample numbers, click here]