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Microcytic anemias and iron studies

15 min

  • Classify an anemia pattern using MCV and RDW
  • Explain how hepcidin gives low serum iron with normal or high ferritin in inflammation
  • Recognize microcytosis with a preserved RBC count that needs hemoglobin fractionation
  • Recognize iron deficiency on iron studies, including when ferritin is not low

Read the full reference

Try first

Try first

An adult's CBC shows hemoglobin 10.1 g/dL, MCV 78 fL, and RDW 16.8%, with the MCV inside the local reference interval on a repeat run from the same specimen. What does the elevated RDW alongside a borderline-normal MCV suggest?

The next section explains it.

Right. The next section explains why.

The next section explains it.

The next section explains it.

Get the idea

Read the indices in order

Hemoglobin establishes anemia and is checked against hematocrit with the rule of three.1 MCV then sorts the anemia into microcytic, normocytic, or macrocytic, and MCHC flags whether hemoglobin content per cell is reduced.1 RDW is read last among the indices: a normal MCV together with an increased RDW can point to a mixed population that the average alone conceals.1 The red-cell count is read last of all, because thalassemia classically keeps it normal to high even as hemoglobin falls, a discordance iron deficiency rarely produces.2

Iron deficiency progresses in stages

Iron deficiency moves from storage depletion, a falling ferritin, to iron-restricted erythropoiesis, a falling transferrin saturation, and then to iron-deficiency anemia itself.1 A low ferritin strongly supports depleted stores. The World Health Organization uses a ferritin below 15 µg/L to indicate deficiency in otherwise healthy adults, and conditionally allows a value below 70 µg/L in adults with inflammation.3

Inflammation restricts iron without depleting it

Hepcidin, raised by inflammation, binds ferroportin and traps iron inside macrophages and intestinal cells. Serum iron and transferrin saturation fall while ferritin, an acute-phase reactant, stays normal or rises.4 Reading a low serum iron alone as depleted stores misses this pattern. Ferritin, read together with an inflammation marker, separates the two.1

Thalassemia trait keeps the count up

Thalassemia trait produces microcytosis, often marked relative to the mild anemia, with a preserved or increased red-cell count and normal iron studies.2 That combination is a pattern iron deficiency rarely produces, and confirming it needs hemoglobin fractionation, since iron studies alone do not confirm it.2

References
  1. Keohane EM, Preston MM, Mirza KM, Walenga JM, eds. Rodak's Hematology: Clinical Principles and Applications. 7th ed. Elsevier; 2025. Accessed September 26, 2026. https://www.us.elsevierhealth.com/rodaks-hematology-9780323936507.html
  2. Tamary H, Greenberg-Kushnir N, Dgany O. Alpha-thalassemia. GeneReviews. Updated April 23, 2026. Accessed September 26, 2026. https://www.ncbi.nlm.nih.gov/books/NBK1435/
  3. World Health Organization. WHO Guideline on Use of Ferritin Concentrations to Assess Iron Status in Individuals and Populations. World Health Organization; 2020. Accessed September 26, 2026. https://www.who.int/publications/i/item/9789240000124
  4. Fletcher A, Forbes A, Svenson N, Thomas DW. Guideline for the laboratory diagnosis of iron deficiency in adults (excluding pregnancy) and children. Br J Haematol. 2022;196(3):523-529. doi:10.1111/bjh.17900

Watch one

A patient's CBC shows hemoglobin 9.6 g/dL, hematocrit 30%, RBC count 5.4 × 10⁶/µL, MCV 66 fL, MCH 24 pg, MCHC 32 g/dL, and RDW 13.8%. Read the pattern before iron studies return.

  1. Confirm anemia and internal consistency: hemoglobin 9.6 g/dL centers the expected hematocrit at about 29%, and the reported 30% fits.

    Hemoglobin is the primary measure of anemia, and hematocrit checks it with the rule of three.

  2. Read the MCV: 66 fL is microcytic.

    MCV sorts the anemia into a broad category before finer testing.

  3. Read the MCHC: 32 g/dL is within the reference interval.

    MCHC flags whether hemoglobin content per cell is markedly reduced.

  4. Read the RDW: 13.8% is within the local interval.

    RDW shows whether the cell population is uniform or mixed.

  5. Read the RBC count: 5.4 × 10⁶/µL, at the high end of normal and preserved for this degree of anemia.

    The red-cell count is read last, because a count preserved relative to the degree of anemia is a discordance thalassemia produces and iron deficiency rarely does.

The pattern is microcytic anemia with a preserved red-cell count and a normal RDW, more consistent with thalassemia trait than iron deficiency. Hemoglobin fractionation and iron studies confirm the pattern before either is reported.

Your turn

Problem 1 of 3

Microcytosis accompanies low ferritin, low serum iron, high TIBC, and low transferrin saturation. Which pattern is most strongly supported?

Incorrect. Inflammation usually produces normal or high ferritin with low or normal TIBC. Coexisting iron deficiency may modify it.

Correct. Depleted ferritin together with increased binding capacity and low saturation supports iron deficiency.

Incorrect. Thalassemia trait can produce microcytosis, but the depleted iron pattern requires an iron-deficiency explanation.

Hint
  1. Read ferritin, serum iron, TIBC, and transferrin saturation together, as one picture.
  2. Inflammation usually raises or normalizes ferritin.
  3. A depleted-stores pattern shows a low ferritin together with a high binding capacity.

Review Microcytic anemia patterns

Problem 2 of 3

An adult has hemoglobin 11.0 g/dL, MCV 64 fL, RBC count 5.8 × 10⁶/µL, ferritin 110 µg/L, and transferrin saturation 28%. Which pattern fits, and why does it not call for an iron-deficiency diagnosis?

Iron deficiency this severe would also show a falling RBC count and depleted iron studies. Marked microcytosis with a preserved or increased RBC count and normal iron studies is the thalassemia-trait pattern, and calling it iron deficiency skips the hemoglobin fractionation that would confirm it.

Called a thalassemia-trait pattern iron deficiency

Thalassemia trait gives marked microcytosis with a preserved or increased RBC count and normal iron studies, a combination iron deficiency rarely produces. Calling it iron deficiency skips the hemoglobin fractionation that would show the raised Hb A2, and iron deficiency itself lowers Hb A2 when both are present.

The RBC count is preserved and even mildly increased despite the marked microcytosis, and ferritin and transferrin saturation are both normal. That combination fits thalassemia trait. Fractionation confirms it.

Anemia of inflammation usually shows a low or low-normal transferrin saturation together with a normal or increased ferritin. The transferrin saturation here sits within its reference interval.

Hint
  1. Compare the RBC count with what iron deficiency usually does to it.
  2. Check whether the iron studies show any evidence of depletion or restriction.

Review Thalassemia syndromes

Problem 3 of 3

A hospitalized patient with a chronic inflammatory illness has hemoglobin 10.2 g/dL, MCV 84 fL, ferritin 180 µg/L, serum iron 32 µg/dL, TIBC 220 µg/dL, and transferrin saturation 12%. Which pattern fits?

Serum iron falls in iron deficiency and in inflammation alike. Ferritin here is increased and TIBC is low, a combination that argues against depleted stores.

Read low serum iron in inflammation as depleted stores

Hepcidin traps iron inside macrophages, so serum iron and transferrin saturation fall, ferritin stays normal or rises, and TIBC is low or normal. Reading the low serum iron alone as iron deficiency misclassifies anemia of inflammation. Coexisting deficiency is judged from ferritin read with an inflammation marker.

Hepcidin lowers serum iron and transferrin saturation while ferritin, an acute-phase reactant, stays normal or rises, and TIBC runs low or normal. That is the pattern shown here.

Thalassemia trait usually shows more striking microcytosis relative to the anemia, with normal iron studies. Here the iron studies themselves are abnormal.

Review Anemia of inflammation

Use it

  • A woman in her thirties reports fatigue and heavy monthly bleeding for the past several months.
  • She has no history of chronic illness, fever, or recent infection.
  • A CBC 6 months ago showed hemoglobin 12.8 g/dL, MCV 89 fL.
  • Serum and EDTA specimens are collected together this visit for a CBC and iron studies.
TestResultPreviousReference intervalFlag
Hemoglobin8.9 g/dL12.8 g/dL6 months ago12.0–15.5 g/dLLow
MCV68 fL89 fL6 months ago76–100 fLLow
RDW18.2 %11.5–14.5 %High
RBC count4.0 × 10⁶/µL4.3 × 10⁶/µL6 months ago4.00–6.00 × 10⁶/µL
Ferritin8 µg/L15–150 µg/LLow
Serum iron22 µg/dL50–170 µg/dLLow
TIBC480 µg/dL250–425 µg/dLHigh
Transferrin saturation5 %20–50 %Low

Specimen: H 5, L 8, I 2. Serum for iron studies; EDTA for CBC, collected together.

Decision 1 of 3

How does the anemia classify from these indices?

The MCV is 68 fL, below the 76 fL lower limit shown here, and the RDW is well above the reference interval. Neither is normal.

MCV 68 fL is microcytic, and RDW 18.2% is increased. The increased RDW shows red cells of unequal size, a common finding as iron deficiency develops.

The MCV is decreased here, and the RDW is raised. Neither matches a macrocytic, uniform pattern.

Review Establishing the anemia pattern

Decision 2 of 3

Which pattern do the iron studies and RBC count support?

Thalassemia trait keeps the RBC count preserved or increased with normal iron studies. Here the RBC count has fallen from 4.3 to 4.0 × 10⁶/µL, and every iron study is abnormal.

Ferritin 8 µg/L is low, transferrin saturation 5% is low, and TIBC 480 µg/dL is increased. Depleted stores and restricted delivery together with the microcytic, high-RDW anemia support iron deficiency.

Anemia of inflammation usually keeps ferritin normal or increased with a low or normal TIBC. Ferritin here is low and TIBC is increased, the opposite pattern.

Review Microcytic anemia patterns

Decision 3 of 3

After 3 months of iron therapy and an intercurrent viral illness, repeat testing shows ferritin 90 µg/L, transferrin saturation still low at 9%, and TIBC still increased. Does the normal ferritin rule out ongoing iron deficiency?

Ferritin is an acute-phase reactant, and the intercurrent illness can raise it even with stores still depleted. A single normal ferritin during inflammation does not rule out iron deficiency.

Excluded iron deficiency because ferritin was not low

Ferritin is an acute-phase reactant, so inflammation, liver disease, or malignancy can keep it normal or high in a patient with depleted stores. Transferrin saturation, TIBC, an inflammation marker, and the CBC show the deficiency. WHO allows a ferritin below 70 µg/L to indicate it in adults with inflammation.

Transferrin saturation and TIBC still show restricted, depleted-pattern iron delivery. Ferritin needs to be read with an inflammation marker before it clears the patient of ongoing deficiency.

A marrow iron stain is not the routine next step. Transferrin saturation, TIBC, and an inflammation marker read alongside ferritin already answer the question here.

Review Microcytic anemia patterns

The clue that settles this case is the shape of the iron studies. A falling RBC count, a low ferritin, a high TIBC, and a low transferrin saturation together support depleted stores from ongoing blood loss, the pattern of iron deficiency.

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