Microcytic Anaemia That Iron Tablets Will Not Fix
A 26-year-old woman reports six months of fatigue and breathlessness on one flight of stairs. She is a lifelong vegetarian, has heavy menstrual bleeding, and takes no supplements. Examination shows pale conjunctivae, no icterus, no organomegaly, and BMI 19. Full blood count: haemoglobin 9.6 g/dL, RBC 5.6 × 10¹²/L, MCV 66 fL, MCH 21 pg, RDW 15.8 %, platelets 310 × 10⁹/L, WBC 7.2 × 10⁹/L, reticulocytes 1.1 %. Serum ferritin 95 µg/L (reference 15–150), with serum iron and total iron-binding capacity both within reference range; CRP is normal. Her mother and a maternal uncle have had 'mild anaemia since childhood' that never responded to iron tablets. The clinic's standing protocol is to start three months of oral iron for any haemoglobin below 10 g/dL with MCV below 80 fL, and the prescription is already written.
1. Which findings fit iron-deficiency anaemia, and which do not? What is the most likely diagnosis?
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Findings that fit iron deficiency
- Hb 9.6 g/dL with MCV 66 fL and MCH 21 pg: microcytic, hypochromic anaemia.
- Heavy menstrual bleeding and a vegetarian diet: genuine risk factors.
- Mildly raised RDW (15.8 %): anisocytosis, common in iron deficiency.
Findings that argue strongly against it
- Ferritin 95 µg/L is comfortably normal; iron deficiency virtually always drives ferritin below 30, usually below 15. (Ferritin is an acute-phase protein, but CRP is normal, so there is no inflammatory elevation to explain it away.)
- Serum iron and TIBC are normal - in iron deficiency, iron falls and TIBC rises.
- The RBC count is high (5.6 × 10¹²/L) for this degree of anaemia. Iron deficiency reduces the number of cells produced; thalassaemia trait produces many small cells.
- Mentzer index = MCV/RBC = 66/5.6 = 11.8 (below 13 favours thalassaemia trait).
- Family history of anaemia since childhood that did not respond to iron.
Most likely diagnosis: beta-thalassaemia trait (microcytic anaemia with normal iron stores, high RBC count, positive family history). Alpha-thalassaemia trait could produce a similar picture but usually gives a normal HbA2.
2. What is the risk of simply following the clinic protocol and giving three months of oral iron, and what single investigation should be done first?
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Risks of the protocol here
- Iron loading without deficiency. The patient's stores are already normal. Unnecessary iron is not excreted efficiently; repeated courses risk haemosiderosis, particularly in a person who may need lifelong monitoring.
- Diagnostic delay and mislabelling. If the Hb rises slightly (from better diet, less bleeding, or regression to the mean), the chart will read 'iron-responsive anaemia' and the true cause is buried. The same mistake already happened in her mother and uncle.
- Side effects and adherence guilt. Nausea, constipation and black stools are then read as 'non-compliance' rather than as evidence the diagnosis was wrong.
- Missed genetic counselling. A trait carrier's reproductive risk stays invisible until a partner is screened.
First investigation: haemoglobin A2 quantification (HbA2 above about 3.5 % establishes beta-thalassaemia trait), interpreted with the ferritin already in hand. If HbA2 is normal, alpha-thalassaemia or a rarer variant should be considered, and iron deficiency would have to be re-excluded with a soluble transferrin receptor or a therapeutic trial judged on ferritin, not on Hb alone.
Conclusion: the protocol's Hb/MCV trigger is a screening prompt, not a diagnosis; the abnormal iron profile should have stopped the prescription.
3. Assume beta-thalassaemia trait is confirmed and her partner's full blood count is completely normal. What would you tell the couple about their children, and what caveat applies?
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Genetics. Beta-thalassaemia trait is autosomal recessive. If one parent is a carrier (genotype β/β⁺ or β/β⁰) and the other has two normal beta-globin alleles (β/β), each child independently has:
- 50 % chance of thalassaemia trait (carrier, like the mother)
- 50 % chance of being completely unaffected (two normal alleles)
- 0 % chance of thalassaemia major, because the child cannot inherit a thalassaemic allele from the unaffected parent.
What this means practically. No prenatal testing is indicated for this couple on these grounds. Children who are carriers need a blood count at some point (usually before marriage or pregnancy) so that their own partner can be screened; carriers are usually asymptomatic or mildly anaemic.
The caveat. A 'normal full blood count' does not formally exclude carrier status - a silent alpha-thalassaemia carrier can have a normal or near-normal count, and a beta carrier can occasionally have only borderline indices. If the partner's MCV and MCH are normal, beta-thalassaemia major is effectively excluded; if any doubt remains, the partner should have HbA2 and, where indicated, molecular testing before the couple is reassured that the risk is zero.