Abdul Mannan: Why Thalassaemia Is More Than Low Haemoglobin
Abdul Mannan, Consultant Haematologist at Betsi Cadwaladr University Health Board, shared a post on LinkedIn:
”Alpha never leaves.
It has been there since your very first embryonic cells. The same chain. Constant. Its partner, though, is where the story begins.
Here is how haemoglobin changes from embryo to adult:
- Very early embryo: zeta joins epsilon to form Hb Gower one.
- Fetal life: alpha joins gamma to form HbF, the dominant haemoglobin before birth.
- Late fetal life and birth: gamma gradually decreases while beta increases, so HbA begins to appear.
- Adult life: about ninety six to ninety eight percent HbA, up to three percent HbA2, and only a very small amount of HbF remains.
The beta-like chain is the real shape shifter.
Epsilon becomes gamma, gamma becomes beta, and a small amount becomes delta.
Each transition is tightly controlled by development, not random chance.
And this is the part that changes how you think about thalassaemia.
The problem is not only low haemoglobin. The real problem is chain imbalance.
When beta chains are reduced, extra alpha chains are left unmatched. They precipitate inside the cell, damage the membrane, and shorten red cell survival. That is the disease mechanism.
It also explains why HbF reactivation works.
Hydroxyurea and newer gene therapies do not simply increase haemoglobin numbers. They bring gamma chains back and partially reverse the developmental switch toward adult haemoglobin.
Adult haemoglobin fractions adapted from Rosove, 2024.
What is the biggest misconception your trainees have about haemoglobin switching?”
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