In β-thalassemia major, which hemoglobin type is characteristically elevated on hemoglobin electrophoresis?

Explanation

## Hemoglobin Electrophoresis Pattern in β-Thalassemia Major **Key Point:** β-thalassemia major shows **absent or severely reduced HbA**, **elevated HbF**, and **elevated HbA~2~** on hemoglobin electrophoresis. ### Hemoglobin Composition in β-Thalassemia Major | Hemoglobin | Normal % | β-Thalassemia Major | Reason | | --- | --- | --- | --- | | HbA (α~2~β~2~) | 96–98% | <10% or absent | β-globin chain deficiency | | HbF (α~2~γ~2~) | <1% | **30–90%** | **Compensatory ↑ γ-globin synthesis** | | HbA~2~ (α~2~δ~2~) | 2–3% | **4–6%** | Slight ↑ δ-globin synthesis | **High-Yield:** The **markedly elevated HbF** is the most characteristic finding and distinguishes β-thalassemia major from other hemolytic anemias. HbF does NOT contain β-globin chains, so it is unaffected by β-globin deficiency. ### Mechanism of HbF Elevation 1. Severe β-globin deficiency triggers compensatory γ-globin gene expression 2. γ-globin chains combine with α-globin → HbF production 3. HbF is **protective** against hemolysis (no precipitating α-globin chains in HbF) 4. Patients with higher HbF levels have milder disease (HPFH phenotype) **Clinical Pearl:** Patients with hereditary persistence of fetal hemoglobin (HPFH) who are homozygous for β-thalassemia mutations remain asymptomatic because they produce sufficient HbF to prevent α-globin precipitation. **Mnemonic:** **FAD** — **F**etal hemoglobin ↑, **A**bsent HbA, **D**elta (HbA~2~) ↑ in β-thalassemia major. [cite:Harrison 21e Ch 104]