When Is Iron Deficiency Anemia Not What It Appears to Be?

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SometimesI get referrals for patients with iron deficiency anemia who aren’t responding to iron.  These patients can have been on iron supplementation for months to years with little to no improvement in anemia.  Reason 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 required daily in your diet.  Including iron rich foods in your diet is helpful but iron supplementation must be continued until 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 as it 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 is repeated. If your body is able to absorb iron, the level will increase dramatically.  If there is little to no improvement, your doctor may recommend IV iron.   
  • Wrong diagnosis:  The most common 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 disorder of hemoglobin, a protein in the 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 iron deficiency anemia. There are two major types of thalassemia, alpha and beta.  

Why do people with thalassemia trait get 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 he/she has  anything to eat, the iron level might be low just because he/she hasn’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.

How can you distinguish 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 physician rules out iron deficiency and beta thalassemia trait.  Once these two diagnoses are ruled out, alpha thalassemia trait is the presumptive diagnosis.  

So how I can improve the 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 any health issues.  

Why is 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 a moderate anemia to severe anemia requiring monthly blood transfusions.    

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