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William Aird: Thalassemia Trait or Iron Deficiency?
William Aird/X
Aug 30, 2026, 12:57

William Aird: Thalassemia Trait or Iron Deficiency?

William Aird, Professor of Medicine at Harvard Medical School, shared a post on LinkedIn:

“Thalassemia trait or iron deficiency?

There are all sorts of formulas designed to distinguish the two in a patient with microcytosis.

The Mentzer index may be the best known:

MCV devided by RBC count

Less than 13 suggests thalassemia trait.

Greater than 13 suggests iron deficiency.

Easy enough to memorize.

But why does it work?

Here is the thought experiment.

Imagine red cells suddenly become smaller.

If the RBC count stays the same, each cell carries less hemoglobin, so the total amount of hemoglobin carried by the circulating red cells falls.

That reduces oxygen-carrying capacity.

The kidney senses the change and increases erythropoietin.

Now the two conditions diverge.

In thalassemia trait, iron is available.

The marrow can respond to the erythropoietic drive by making more red cells.

In iron deficiency, the EPO signal is also there, but the marrow is iron-limited.

It cannot increase red cell production to the same degree.

So for a given degree of microcytosis:

Thalassemia trait – relatively more red cells

Iron deficiency – relatively fewer red cells

And now the Mentzer index makes sense.

The formula is not magic.

It is physiology compressed into arithmetic.”

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