Microcytic anaemia: four causes, four iron fingerprints
In microcytic anaemia, small red cells look alike under the microscope, but each cause breaks a different step of haemoglobin making. The iron studies, the red cell count and HbA₂ show which step failed.
Chapters (12)
Distinguish iron deficiency, anaemia of inflammation, thalassaemia and sideroblastic anaemia using the mechanism of impaired haemoglobin synthesis and the iron studies.
The short version
- Small red cells come from four failures: iron absent, iron locked away, iron that cannot be used, or unbalanced globin chains.
- Ferritin and iron-binding capacity sort the first two causes: iron deficiency has low ferritin and high iron-binding capacity; anaemia of inflammation has normal or high ferritin and low or normal iron-binding capacity.
- Sideroblastic anaemia has high iron, ferritin and transferrin saturation, with ringed sideroblasts in the marrow.
- Thalassaemia trait leaves the iron studies normal, with a high red cell count, target cells and, in the beta form, a raised HbA₂.
- The Mentzer index (MCV ÷ red cell count) under 13 favours thalassaemia over iron deficiency, but it is only a rough screen.
What microcytic anaemia means
Haemoglobin has two parts: haem, which is iron held in a ring called protoporphyrin, and globin, the protein chains.[1][4]
A red cell short of either part carries less haemoglobin, so it is smaller and paler: microcytic and hypochromic.[2][13] Microcytic anaemia is anaemia with a mean cell volume (MCV) below 80 fL.[11]
The opening puzzle shows why a count alone is not enough. A 29-year-old woman has haemoglobin 8.4 g/dL and an MCV of 72 fL. Her neighbour, a man with long-standing rheumatoid arthritis, has almost the same blood count. She has no iron to spare; he has iron that is locked away. Telling them apart is the point of the lesson.
Four ways to make small red cells
Each cause breaks a different step of haemoglobin making.[2][13]
- Iron deficiency: not enough iron.
- Anaemia of inflammation: iron locked away.
- Sideroblastic anaemia: iron that cannot be built into haem.
- Thalassaemia: unbalanced globin chains.
| Cause | What fails | Iron studies |
|---|---|---|
| Iron deficiency | Iron stores run out | Ferritin low (below 30 ng/mL), serum iron and transferrin saturation low, iron-binding capacity high |
| Anaemia of inflammation | Iron locked in macrophages | Serum iron low, ferritin normal or high, iron-binding capacity low or normal |
| Sideroblastic anaemia | Iron cannot enter protoporphyrin | Serum iron, ferritin and transferrin saturation all high |
| Thalassaemia trait | Globin chains unbalanced | Iron studies normal (other clues: high red cell count, target cells, raised HbA₂ in beta trait) |
Iron deficiency: the stores run out
Ferritin, the storage protein, falls. A ferritin below 30 ng/mL is specific for iron deficiency.[2][6]
The liver makes more transferrin to catch every atom of iron, so the total iron-binding capacity (TIBC) rises, while serum iron and transferrin saturation fall.[2][6]
Anaemia of inflammation: iron present but locked
Here iron is present, but hepcidin, driven by interleukin 6, locks it inside macrophages.[3][7] Serum iron is low, but ferritin is normal or high, because ferritin is an acute-phase reactant.[2][3][6] It is usually normocytic at first and becomes microcytic only in some patients over time.[3]
Transferrin falls in inflammation, so the iron-binding capacity is low or normal, not high.[3][6]
Sideroblastic anaemia: iron everywhere, not used
Sideroblastic anaemia breaks haem synthesis itself. Iron is plentiful, but mitochondria cannot put it into protoporphyrin, so it piles up around the nucleus. These are ringed sideroblasts on a marrow iron stain. Serum iron, ferritin and transferrin saturation are all high.[4][14]
The commonest inherited form is X-linked, a fault in ALAS2, an enzyme that needs vitamin B₆. Alcohol, isoniazid, lead and copper deficiency can cause it too.[4][12] The inherited form is usually microcytic.[4][15]
Thalassaemia trait: globin imbalance, normal iron
Thalassaemia leaves haem alone and unbalances the globin chains.[5][8]
In thalassaemia trait the iron studies are normal, but the red cell count is high for the haemoglobin, and the smear shows target cells.[5][8][9] In beta-thalassaemia trait, haemoglobin electrophoresis shows a raised HbA₂ (above 3.5%).[8] In alpha-thalassaemia, HbA₂ is generally normal.[5]
Under 13 favours thalassaemia over iron deficiency; a rough screen only.[8][10]
Back to the two patients
Her ferritin is 9 ng/mL and her iron-binding capacity is high: iron deficiency. His ferritin is 200 ng/mL, with low iron and a low iron-binding capacity: anaemia of inflammation.[2][3][6]
Same small red cells, opposite iron stores.
| Woman, 29 | Neighbour with rheumatoid arthritis | |
|---|---|---|
| Ferritin (ng/mL) | 9 | 200 |
| Iron-binding capacity | High | Low |
| Diagnosis | Iron deficiency | Anaemia of inflammation |
Practice question
Original · USMLE styleA 24-year-old man of Mediterranean descent is found to be anaemic on routine screening. He is well and has no chronic illness. Haemoglobin is 11.2 g/dL, mean corpuscular volume (MCV) is 66 fL and the red cell count is 5.8 × 10¹²/L. Serum ferritin is 118 ng/mL and transferrin saturation is 32%. The peripheral smear shows microcytes and target cells. Haemoglobin electrophoresis shows haemoglobin A₂ of 5%.
Common questions
What is microcytic anaemia?
Anaemia with a mean cell volume below 80 fL. The red cells are small and pale because they carry less haemoglobin.
What are the four causes of microcytic anaemia?
Iron deficiency, anaemia of inflammation, sideroblastic anaemia and thalassaemia. Each breaks a different step of haemoglobin making: iron absent, locked away, unusable, or unbalanced globin chains.
How do you tell iron deficiency from anaemia of inflammation?
Use ferritin and iron-binding capacity. Iron deficiency has a low ferritin (below 30 ng/mL) and a high iron-binding capacity. In anaemia of inflammation ferritin is normal or high and the iron-binding capacity is low or normal.
What does the Mentzer index show?
It is the MCV divided by the red cell count. A result under 13 favours thalassaemia over iron deficiency, but it is only a rough screen.
What are ringed sideroblasts?
Erythroblasts in which iron has piled up around the nucleus, seen on a marrow iron stain. They mark sideroblastic anaemia, where iron cannot be built into haem.
Transcript
Read the full narration, by chapter674 words
0:00Same small red cells, two different patients
A 29-year-old woman has haemoglobin of 8.4 g/dL and an MCV of 72 femtolitres. Her neighbour, a man with long-standing rheumatoid arthritis, has almost the same blood count. Same small red cells, but she has no iron to spare, and he has iron he cannot use. How do we tell them apart? Today: sort the four causes of microcytic
0:23Today's plan, haemoglobin = haem + globin, and what microcytic means (MCV)
anaemia by the step in haemoglobin making that each one breaks. Haemoglobin has two parts: haem, which is iron held in a ring called protoporphyrin, and globin, the protein chains. A red cell short of either part carries less haemoglobin, so it is smaller and paler: microcytic and hypochromic. Microcytic means a mean cell volume below 80 femtolitres. So there are four ways to fail:
0:52Four places the chain can break
not enough iron, in iron deficiency; iron locked away, in anaemia of inflammation; iron that cannot be built into haem, in sideroblastic anaemia; and unbalanced globin chains, in thalassaemia. Iron deficiency first:
1:09Iron deficiency: low ferritin, high iron-binding capacity
the stores run out. Ferritin, the storage protein, falls; below 30 nanograms per millilitre is specific for iron deficiency. The liver makes more transferrin to catch every atom of iron, so the total iron-binding capacity rises, while serum iron and transferrin saturation fall.
1:30Anaemia of inflammation: iron locked in macrophages
Anaemia of inflammation is the opposite story: iron is present, but hepcidin, driven by interleukin six, locks it inside macrophages. Serum iron is low, but ferritin is normal or high, because ferritin is an acute-phase reactant. And transferrin falls in inflammation, so the iron-binding capacity is low or normal, not high.
1:55Sideroblastic anaemia: iron everywhere, not used
Sideroblastic anaemia breaks haem synthesis itself. Iron is plentiful, but mitochondria cannot put it into protoporphyrin, so it piles up around the nucleus: ringed sideroblasts on a marrow iron stain. Serum iron, ferritin and transferrin saturation are all high. The commonest inherited form is X-linked,
2:16ALAS2, vitamin B6 and the acquired causes
a fault in ALAS2, an enzyme that needs vitamin B6. Alcohol, isoniazid, lead and copper deficiency can cause it too. The inherited form is usually microcytic.
2:32Thalassaemia trait: globin imbalance, high RBC count, target cells, Mentzer index
Thalassaemia leaves haem alone and unbalances the globin chains. In thalassaemia trait the iron studies are normal, but the red cell count is high for the haemoglobin, and the smear shows target cells. Dividing MCV by the red cell count, a result under 13 favours thalassaemia over iron deficiency, though it is only a rough screen. In beta thalassaemia trait, electrophoresis shows a raised haemoglobin A2.
3:02Back to the two patients
Back to our two patients. Her ferritin is nine and her iron-binding capacity is high: iron deficiency. His ferritin is 200, with low iron and a low iron-binding capacity: anaemia of inflammation. Same small red cells, opposite iron stores.
3:21Practice question
Your turn. A 24-year-old man of Mediterranean descent is found to be anaemic on routine screening. He is well and has no chronic illness. Haemoglobin is 11.2 grams per decilitre, MCV 66 femtolitres and red cell count 5.8 times 10 to the twelfth per litre. Serum ferritin is 118 nanograms per millilitre, and transferrin saturation is 32%. The smear shows microcytes and target cells, and electrophoresis shows haemoglobin A2 of 5%. What is the most likely diagnosis? A, iron deficiency anaemia. B, beta-thalassaemia trait. C, alpha-thalassaemia trait. D, anaemia of inflammation. E, sideroblastic anaemia. Pause here and decide. A is out: his ferritin and transferrin saturation
4:20Answer and explanation
show that iron stores are not depleted. C is out: alpha-thalassaemia trait has a normal haemoglobin A2. D is out: he has no inflammatory disease, and a raised A2 points to a globin defect. E is out: sideroblastic anaemia raises iron, ferritin and saturation, with ringed sideroblasts, and gives no raised A2. So the answer is B. A high red cell count, target cells, normal iron studies and a raised haemoglobin A2 make beta-thalassaemia trait.
4:59Recap and next lesson
Three things to keep. One: small red cells come from four failures: iron absent, locked, unusable, or unbalanced globin. Two: ferritin and iron-binding capacity sort the first two; sideroblastic has high iron everywhere; thalassaemia trait has normal iron studies. Three: thalassaemia means a high red cell count, target cells, and, in the beta form, a raised A2. Next, how hepcidin separates iron deficiency from anaemia of inflammation.
Sources
Numbers in the text, e.g. [1], point here- OpenStax. Anatomy and Physiology 2e, 18.3 Erythrocytes. openstax.org/books/anatomy-and-physiology-2e/pages/18-3-erythrocytes
- MSD Manual Professional Version. Iron Deficiency Anemia. msdmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/iron-deficiency-anemia
- MSD Manual Professional Version. Anemia of Chronic Disease. msdmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/anemia-of-chronic-disease
- MSD Manual Professional Version. Sideroblastic Anemias. msdmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/sideroblastic-anemias
- MSD Manual Professional Version. Thalassemias. msdmanuals.com/professional/hematology-and-oncology/anemias-caused-by-hemolysis/thalassemias
- Nairz M, et al. Iron deficiency and anaemia of inflammation. 2016. europepmc.org/article/PMC/PMC5065583
- Lanser L, et al. 2021. europepmc.org/article/PMC/PMC8619077
- Patra et al. Beta-thalassaemia trait vs iron deficiency (Mentzer index, HbA2). 2025. europepmc.org/article/PMC/PMC12705022
- Lazarte et al. 2015. europepmc.org/article/PMC/PMC4615862
- Medicine 2026, Mentzer index cut-off study. europepmc.org/article/PMC/PMC12975230
- Mayo Clin Proc 2005, classification of anaemia by MCV. europepmc.org/article/PMC/PMC7127472
- Understanding Sideroblastic Anemia, J Blood Med 2020. europepmc.org/article/PMC/PMC7524202
- Microcytic anemia. Wikipedia (secondary). en.wikipedia.org/wiki/Microcytic_anemia
- Liu et al. 2026, sideroblastic anaemia case report (ring sideroblasts, iron loading). europepmc.org/article/PMC/PMC13283894
- Inherited microcytic anaemias including congenital sideroblastic anaemia. 2026. europepmc.org/article/PMC/PMC13579797
The two opening patients are a hypothetical teaching vignette. Typical values vary between laboratories; the Mentzer index is a rough screen, not a diagnosis.
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (cropped, recoloured, outlined): erythrocyte, rheumatoid arthritis hand, mitochondria, liver. Macrophage icon by Servier via Bioicons (bioicons.com), CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/), adapted (cropped, recoloured, outlined). Alcohol icon: Health Icons (CC0). Pill icon: Marcel Tisch via Bioicons (CC0). The haem ring, iron jars, iron-studies table, ringed sideroblast, target cells, globin seesaw, Mentzer card, electrophoresis strip and all handwriting are drawn in code (original).
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-HEME-001.
For exam study only, not medical advice. Read the medical disclaimer.
In this series
Playlist on YouTube- EP 01Microcytic anaemia: four causes, four iron fingerprints5:37
- EP 02Hepcidin: why iron falls in inflammation5:34
- EP 03B12 vs folate deficiency: MMA, homocysteine and the nerves5:23
- EP 04Intravascular vs extravascular haemolysis: site and labs5:27
- EP 05G6PD deficiency vs hereditary spherocytosis, by mechanism5:36
- EP 06Sickle cell disease pathophysiology: HbS to vaso-occlusion5:26
- EP 07Primary haemostasis: platelet adhesion, activation and aggregation5:53
- EP 08Coagulation cascade: PT vs aPTT, pathway by pathway5:21
- EP 09Von Willebrand disease vs haemophilia: the labs that separate them5:32
- EP 10Anticoagulants: target, monitoring test and reversal agent5:34
- EP 11Heparin-induced thrombocytopenia: why a low count clots5:29
- EP 12DIC vs TTP vs HUS: mechanism and the PT/PTT5:33
- EP 13AML vs ALL vs CML vs CLL: leukemia classification made simple5:44
- EP 14Oncogenes vs tumour suppressor genes: one hit or two5:17