When Iron Deficiency Anemia Is Not What It Appears to Be

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Sometimes, people with iron deficiency anemia don't respond to treatment with iron supplementation and may go months to years with little to no improvement in anemia. This can happen if the dose is too low or may be due to factors such as missed doses or poor timing of doses.

However, if there aren't improvements even after making adjustments to the dosage and/or taking the supplement as directed, it may mean that the body isn't absorbing iron properly or that the anemia is actually due to thalassemia, an inherited blood disorder.

This article explores the reasons why iron supplements may not be working and why thalassemia often gets mislabeled as an iron deficiency.

Why Iron Supplements May Not Work

Reasons for a lack of response to iron therapy may include:

  • Iron supplementation is too low. Once you develop iron deficiency anemia, you need more than the amount most people require daily in their diet. Including iron-rich foods in your diet is helpful, but iron supplementation must be continued until the condition is fully resolved.
  • It isn't taken as directed: Taking iron isn’t always easy, especially for little ones who have to take the liquid. Iron should be taken on an empty stomach. Consider taking it with a little orange juice to improve absorption. Avoid taking it with milk, which can block the absorption of iron.
  • There's too much milk intake. Iron deficiency anemia in toddlers is often associated with excessive milk intake. Reducing milk intake is an important part of treatment.
  • The body resists absorbing the iron. Some patients may have difficulty absorbing iron in the intestine. This can be determined by an iron absorption test.
  • The anemia is caused by another condition. The most commonly missed diagnosis is a thalassemia trait, meaning you may not have symptoms, or you may only have mild anemia.

Iron Absorption Test

For an iron absorption test, your iron levels are checked after fasting (having nothing to eat or drink) for a period of time. You are then given a dose of iron, and the iron level test is repeated. If your body is able to absorb iron, your iron level will increase dramatically. If there is little to no improvement, your healthcare provider may recommend iron infusions, or intravenous iron that's given through a vein.

Thalassemia Trait

Thalassemia is a condition in which the body makes less hemoglobin, a protein that's an important part of red blood cells, than it should, causing anemia. This is known as hemolytic anemia.

This condition means the body lacks enough red blood cells to carry enough oxygen to tissues throughout the body. As a result, you may often feel weak or tired.

Even with mild anemia, the blood cells may be unusually small. This is called microcytosis. It may sound serious, but it's really only a descriptor since red blood cells are described by their hemoglobin content as well as their size.

People who are carriers of thalassemia, also called thalassemia trait, might be mislabeled as having iron deficiency anemia. There are two major types of thalassemia: alpha and beta.

Alpha globin and beta globin are the building blocks of hemoglobin. Those with alpha thalassemia don't make enough alpha globin and those with beta thalassemia don't make enough beta globin.

Why Thalassemia Trait Gets Mislabeled as Iron Deficiency Anemia  

The lab values are very similar in iron deficiency and thalassemia trait. On first glance of the complete blood count (CBC), hemoglobin will be low. This points to anemia and the fact that the corpuscular volume (MCV), or size of the red blood cells, is low. The large majority of people with these changes on CBC have iron deficiency anemia.

Testing for iron deficiency can be tricky. The iron level is influenced by diet. If a patient undergoes testing first thing in the morning, before they have anything to eat, their iron level might be low because they haven’t yet ingested anything with iron. A more helpful test is the ferritin level, which measures the storage of iron in the body. A low ferritin level is consistent with iron deficiency.

Distinguishing Iron Deficiency Anemia From Thalassemia Trait

The first difference is in the red blood cell count (labeled RBC). In iron deficiency, this value is low because the bone marrow is unable to manufacture red blood cells. In thalassemia trait, RBC is normal to elevated. A normal ferritin level can rule out iron deficiency.

A more specific test, sometimes called hemoglobin electrophoresis or hemoglobinopathy evaluation, measures the different types of hemoglobin in our blood. In an adult, there should be hemoglobin A and A2. People with beta thalassemia trait will have elevation in hemoglobin A2 and/or F (fetal).

There is no simple test for alpha thalassemia trait. Usually, the healthcare provider rules out iron deficiency and beta thalassemia trait. Once these two diagnoses are ruled out, alpha thalassemia trait is the presumptive diagnosis.

Find Out if You Have Thalassemia Trait

If you and your partner both have the same thalassemia trait (both alpha or both beta), you have a 1 in 4 (25%) of having a child with thalassemia disease. Thalassemia disease can range from moderate to severe anemia, requiring monthly blood transfusions.


Thalassemia, an inherited condition that results in anemia, is sometimes mislabeled as iron deficiency anemia. A thalassemia diagnosis may be delayed until after the anemia doesn't respond to treatment with iron supplements.

Other reasons that iron supplementation may not improve anemia can be related to issues with absorption, not taking it as directed, or needing a higher dose.

3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Jimenez K, Kulnigg-Dabsch S, Gasche C. Management of iron deficiency anemiaGastroenterol Hepatol (N Y). 2015;11(4):241–250.

  2. Centers for Disease Control and Prevention. What is thalassemia?

  3. Fibach E, Rachmilewitz EA. Pathophysiology and treatment of patients with beta-thalassemia - an updateF1000Res. 2017;6:2156. doi:10.12688/f1000research.12688.1.

By Amber Yates, MD
Amber Yates, MD, is a board-certified pediatric hematologist and a practicing physician at Baylor College of Medicine.