When Iron Deficiency Anemia Is Not What It Appears to Be

plate of black beans
PeopleImages / Getty Images

Sometimes, patients with iron deficiency anemia don't respond to iron. These patients may have been on iron supplementation for months to years with little to no improvement in anemia. Reasons why a patient may not respond to iron therapy 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.
  • Not taking the iron 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. Iron should not be taken with milk, which blocks the absorption of iron.
  • The patient did not reduce milk intake as recommended. Iron deficiency anemia in toddlers is often associated with excessive milk intake. Reducing milk intake is an important part of treatment.
  • Your body is not absorbing the iron. Some patients may have difficulty absorbing iron in the intestine. This can be determined by an iron absorption test. Essentially, 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 intravenous iron.
  • Wrong diagnosis. The most commonly missed diagnosis is thalassemia trait.

Thalassemia Trait

Thalassemia means blood of the sea, as it is associated with the Mediterranean Sea. Today thalassemia can be seen in many ethnic groups and races. Thalassemia is a disorder of hemoglobin, a protein in red blood cells. This results in mild anemia and very small red blood cells (called microcytosis). 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.

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), the hemoglobin will be low indicating anemia and the mean corpuscular volume (MCV), or size of the red blood cell, will be 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 the diet. If a patient has labs drawn first thing in the morning, before they have anything to eat, their iron level might be low just because they haven’t ingested anything with iron recently. A more helpful test is the ferritin level, which measures the storage of iron in your 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.

How to Improve Your Anemia

Treatment is not needed nor recommended. This is a lifelong condition with mild anemia and small red blood cells. People with thalassemia trait should not take iron supplementation, as this will not improve your anemia. Having thalassemia trait should not cause you to have any health issues.

Why It's Important to Know 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.

2 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. 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.