System 2 Thinking Approach to Thalassemia Minor vs. Iron Deficiency Anemia

By William Aird

The 2 most common causes of microcytic anemia are iron deficiency anemia (IDA) and thalassemia trait. According to the morphological classification of anemia, microcytic anemia is divided into normochromic and hypochromic subtypes.

As a general rule IDA is hypochromic, thalassemia normochromic. But the mean corpuscular hemoglobin concentration (MCHC) is by no means perfect at discriminating between the two conditions. Many other discriminant indices and formulas have been proposed over the years.

Perhaps the most commonly used formula is the Mentzer index which is MCV/RBC count:

  • Mentzer index > 13 suggests IDA
  • Mentzer index < 13 is more consistent with thalassemia minor

Let’s look at an example:

If we put on our slow system 2 thinking hat, we can make sense of all these numbers by talking our way through them:

  • The human body has evolved to maximize oxygen delivery to tissues.
  • As such, we operate at an optimal Hb/Hct where the advantages of Hb on oxygen carrying capacity of blood are balanced with the negative effect of Hct on viscosity/total peripheral resistance/cardiac output (remember, Hb/Hct plotted against O2 delivery yields a bell shape curve with the optimal Hb/Hct at the apex).
  • Hct = MCV x RBC count
  • If our red cells become small, say with thalassemia or IDA, the Hct/Hb will fall and the natural impulse (via hypoxia-mediated positive feedback) is for the bone marrow to increase production of RBCs in order to normalize the Hct (and by extension the Hb).
  • Individuals with thalassemia minor have a perfectly healthy bone marrow and are up to the task. As a result, their RBC count is typically increased and their Hct/Hb only minimally reduced, if at all.
  • The bone marrow of those with IDA cannot rise to the occasion and fail to increase RBC production because they are missing an essential nutrient (iron) for proliferation of RBC precursors. For that reason, their RBC count, Hct/Hb are disproportionately low.

Isn’t this a lot more fun/fulfilling than memorizing formulas?