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Microcytic anemias and iron studies

15 min

Skills you'll build4 skills
  • 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

At the bench: Relate red cell indices and morphology to the anemia workup

Try first

Try first

An adult's CBC shows hemoglobin 10.1 g/dL, MCV 78 fL, and RDW 16.8%. This laboratory's MCV reference interval is 76 to 100 fL, and a repeat run on the same specimen gives the same MCV. What does the elevated RDW with an MCV just within the reference interval suggest?

Keep going to see the reasoning.

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

Read the indices in order

Hemoglobin shows anemia. Before interpreting the pattern, check that MCV, MCH and MCHC agree with the hemoglobin, hematocrit and RBC count they are calculated from.1 The rule of three (hematocrit about three times hemoglobin) is a rough check. It works best with normocytic, normochromic cells, and it does not check the RBC count.5 MCV then classifies the anemia as microcytic, normocytic, or macrocytic, and MCHC describes the hemoglobin concentration inside the red cells.1 RDW is reviewed last among the indices. A normal MCV with an increased RDW can point to a mixed population that the average conceals.1 The red-cell count is reviewed 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

Anemia of inflammation

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

Thalassemia trait

Thalassemia trait produces microcytosis, often marked relative to the mild anemia, with a preserved or increased red-cell count and adequate iron stores.2 Hemoglobin fractionation is the next test for this pattern. Adult fractions can be normal in alpha-thalassemia trait. Persistent microcytosis with no other cause may then be referred for molecular testing under the laboratory's procedure.2

Follow the bench demonstration

Sources for this step
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
  5. Gulati G, Uppal G, Gong J. Unreliable automated complete blood count results: causes, recognition, and resolution. Ann Lab Med. 2022;42(5):515-530. doi:10.3343/alm.2022.42.5.515

Watch one

Read each decision and its explanation.

A patient's CBC shows hemoglobin 9.6 g/dL, hematocrit 30%, RBC count 5.4 × 10⁶/µL, MCV 55.6 fL, MCH 17.8 pg, MCHC 32 g/dL, and RDW 13.8%. Check the calculations, then interpret the pattern before iron studies return.

  1. Check the calculated indices. MCV 55.6 fL, MCH 17.8 pg and MCHC 32 g/dL agree with the measured values.

    MCV and MCH are both calculated from the RBC count. Comparing hemoglobin with hematocrit cannot check them.

  2. Review hemoglobin and MCV. A hemoglobin of 9.6 g/dL with MCV 55.6 fL is a microcytic anemia.

    Hemoglobin establishes anemia, and MCV classifies it into a broad category.

  3. Check the MCHC. At 32 g/dL it is within the reference interval.

    MCHC describes the hemoglobin concentration inside the red cells.

  4. Check the RDW. At 13.8% it is within the local interval.

    RDW shows whether the cell population is uniform or mixed.

  5. Check the RBC count. At 5.4 × 10⁶/µL it is at the high end of normal and preserved for this degree of anemia.

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

With RBC count in × 10⁶/µL:

  • MCV = hematocrit (%) × 10 ÷ RBC count = 30 × 10 ÷ 5.4 = 55.6 fL.
  • MCH = hemoglobin (g/dL) × 10 ÷ RBC count = 9.6 × 10 ÷ 5.4 = 17.8 pg.
  • MCHC = hemoglobin × 100 ÷ hematocrit = 9.6 × 100 ÷ 30 = 32 g/dL.

Hemoglobin × 3 gives 28.8%, close to the reported hematocrit of 30%. That rough check covers only those two values.1,5

The preserved RBC count and normal RDW fit a thalassemia pattern. Iron studies and hemoglobin fractionation come before any cause is reported. Adult fractions can be normal in alpha-thalassemia trait, and the laboratory's procedure may then call for molecular testing.2

Practice this skill

Your turn

Problem 1 of 3 · Hints available

A patient with microcytosis has 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 these depleted iron results indicate iron deficiency.

Hint
  1. Interpret ferritin, serum iron, TIBC, and transferrin saturation together.
  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 · Hints available

An adult has persistent microcytosis: hemoglobin 11.0 g/dL, MCV 64 fL and RBC count 5.8 × 10⁶/µL. Ferritin is 110 µg/L and transferrin saturation 28%, with no sign of inflammation. Hemoglobin fractionation shows normal adult fractions. What does the laboratory do next?

Microcytosis alone does not mean iron deficiency. Ferritin and transferrin saturation are normal, so iron stores are adequate.

Adult hemoglobin fractions can be normal in alpha-thalassemia trait. Persistent microcytosis with a preserved RBC count and adequate iron keeps it in the differential. HBA1 and HBA2 testing for deletions and sequence variants is the next step under the laboratory's procedure.

Normal adult fractions do not rule out alpha-thalassemia trait. This unexplained microcytosis is referred for molecular testing under the laboratory's procedure.

Hint
  1. Look at the RBC count and the iron studies together.
  2. Consider which thalassemia trait can show normal adult fractions.

Review Thalassemia syndromes

Problem 3 of 3 · On your own

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 15%. 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. Ferritin, an acute-phase reactant, stays normal or rises, and TIBC is low or normal, as 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

Read the case evidence, then make each decision. The step is complete without 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/dL Low6 months ago: 12.8 g/dL12.8 g/dL6 months ago12.0–15.5 g/dL12.0–15.5Low
MCV68 fL Low6 months ago: 89 fL89 fL6 months ago76–100 fL76–100Low
RDW18.2 % High11.5–14.5 %11.5–14.5High
RBC count4.0 × 10⁶/µL6 months ago: 4.3 × 10⁶/µL4.3 × 10⁶/µL6 months ago4.00–6.00 × 10⁶/µL4.00–6.00
Ferritin8 µg/L Low15–150 µg/L15–150Low
Serum iron22 µg/dL Low50–170 µg/dL50–170Low
TIBC480 µg/dL High250–425 µg/dL250–425High
Transferrin saturation5 % Low20–50 %20–50Low

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

Decision 1 of 3

How do you classify the anemia 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. In adults with inflammation, WHO accepts a ferritin below 70 µg/L as a sign of iron deficiency.

Transferrin saturation and TIBC still show restricted, depleted-pattern iron delivery. Ferritin must be interpreted with an inflammation marker before ongoing deficiency is excluded.

A marrow iron stain is not the routine next step. Transferrin saturation, TIBC, and an inflammation marker interpreted with ferritin are sufficient here.

Review Microcytic anemia patterns

The iron studies show depleted stores. A falling RBC count, a low ferritin, a high TIBC, and a low transferrin saturation together fit iron deficiency from ongoing blood loss.

For reference