Bit · Heme/Onc
Iron deficiency vs ACD vs Thalassemia
Three microcytic anaemias that all show MCV under 80. The pivot is iron studies plus, for thalassemia, hemoglobin electrophoresis.
Mechanism
All three are problems making hemoglobin, but the reason is different:
- Iron deficiency — not enough iron, so not enough heme. Body raises transferrin to scavenge harder.
- Anaemia of chronic disease — inflammation drives hepcidin, which traps iron in macrophages. Iron is in the body but can't get to the marrow.
- Thalassemia — globin chain production is broken (α or β), so even with plenty of iron and heme, hemoglobin can't be assembled.
Differentiator Table
| Iron deficiency | ACD | Thalassemia | |
| MCV | ↓ | ↓ or normal | ↓↓ (often <70) |
| RDW | ↑↑ | Normal | Normal |
| Serum iron | ↓ | ↓ | Normal / ↑ |
| Ferritin | ↓↓ | ↑ (inflammatory) | Normal / ↑ |
| TIBC / Transferrin | ↑ | ↓ | Normal |
| Transferrin saturation | ↓ | ↓ | Normal / ↑ |
| Classic clue | Pica, koilonychia, menorrhagia, NSAIDs | Chronic inflammation, CKD, RA, cancer | Mediterranean / SE Asian ancestry, target cells |
| Diagnostic test | Iron studies | Iron studies + clinical context | Hb electrophoresis |
The Pivot
The single most useful number is ferritin:
- Low ferritin → iron deficiency. Always.
- High ferritin + low serum iron → ACD.
- Normal ferritin with very low MCV and normal RDW → thalassemia (the smoking gun is a low MCV out of proportion to a mild anaemia).
NBME-Style Stem
A 22-year-old woman of Greek descent is evaluated for fatigue. Hemoglobin is 10.2 g/dL, MCV 65 fL, RDW normal. Iron studies are normal. Peripheral smear shows target cells. Hemoglobin electrophoresis shows HbA₂ 5.8%. Which of the following is the most likely diagnosis?
Concept Anchor
Hepcidin is the master iron gate — inflammation drives it up, which locks iron inside macrophages even when the body is full of it. That is why ACD looks like iron deficiency on serum iron but the ferritin betrays the truth.