ß-Thalassemia & co-existing Iron Deficiency

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

science.uottawa.ca

Or More Simply

                        α-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]