Given a lot of questions after a recent tweet on iron deficiency, I thought a #tweetorial might be in order.

Iron deficiency anemia affects a large proportion of the worlds population and iron deficiency is even more common.

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It is more common is females than males and racial disparities exist.

Structural racism contributes to the fact that iron deficiency is seen in 4.3% of Black patients compared to 2% of white patients.
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Interpretation of iron studies is more challenging than you’d think given the fact that multiple indices are affected by variables completely unrelated to iron.

Serum iron = ferric ions (Fe3+) which are largely bound to transferrin in the serum.

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It fluctuates throughout the day with highest levels in AM.

It is highly variable, affected by dietary intake, inflammation, infection.

It is basically useless in my opinion as evidenced by deficient pts that take supplement once, just before labs and iron is

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Transferrin is the principal iron transport protein in plasma and increases in deficiency to maximize utilization of the iron available.

TIBC is analogous as it reflects the availability of iron binding sites on transferrin. (To convert, multiply transferrin x1.389=TIBC)

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Transferrin saturation is calculated from serum iron and TIBC.

It is poorly specific as pregnancy, OCP, chronic illness can lead to low saturation without deficiency.

And it relies on serum iron which we already know is useless!
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Ferritin is the intracellular storage form of iron. A very small amount is found in the serum.

This level is by inflammation, liver disease, heart disease, exercise, and malignancy because ferritin (in the form of apoferritin) is an acute phase reactant.

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In chronic inflammation hepcidin leads to iron sequestration in macrophages, leading to normal or high ferritin levels despite decreased availability in circulation.

Low ferritin IS consistent with iron deficiency!
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Normal cutoffs vary between labs but <30 is supported by international guidelines and bone marrow correlations.

While low ferritin has high specificity for iron deficiency, a normal ferritin does not exclude the diagnosis.

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Soluble transferrin receptor can be used to distinguish iron deficiency (where it will be elevated) and anemia of inflammation (normal) as it is not affected by inflammation.

It is directly proportional to erythropoietic rate and inversely to tissue iron availability.

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It is also elevated in hemolysis and ineffective erythropoiesis.

The soluble transferrin receptor ferritin index can also be calculated and used to differentiate anemia of inflammation vs IDA vs both further.

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Bone marrow is the gold standard for diagnosis but is almost never done for this indication.

Response to supplementation is a less invasive option which is quite helpful as long as the patient is taking iron, able to absorb it, and doesn’t have ongoing losses.

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Other clues to iron deficiency anemia (though not specific!) include low MCV, low MCH and increased RDW though these occur late in the course.

Other less commonly used labs include hepcidin, RBC zinc protoporphyrin, and reticulocyte hemoglobin content.
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Iron deficiency can also affect hemoglobin electrophoresis by decreasing HbA2. This change mimics alpha thalassemia and masks beta thalassemia.

For this reason I typically correct iron status before sending electrophoresis.
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To review,
Ferritin is most helpful but can be falsely elevated in which case soluble transferrin receptor is useful.

Serum iron least helpful but TIBC, if elevated, can support diagnosis.

Trial of iron with improvement in hemoglobin/indices is the best evidence!
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For as common as iron deficiency is, you’d think diagnosis would be more straightforward.

I see so many patients misdiagnosed but it’s really not surprising given the complexity and limitations of the labs available.

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