Iron deficiency anaemia — viva

Opening (must-hit)

"This is a microcytic hypochromic anaemia with a low ferritin and a normal CRP — iron deficiency anaemia, uncomplicated by inflammation. For his age the WHO threshold is below 110 g per litre, so 74 is markedly low. The cause is written into the history: excessive cow's milk at 900 mL per day, early introduction, and the pagophagia is a specific clue to iron deficiency. He is haemodynamically stable, so my plan is oral elemental iron at 3 to 6 mg per kg per day once daily or on alternate days for at least three months, combined with cutting the cow's milk below 500 mL per day and introducing iron-rich solids. I would expect reticulocytes to rise by day 7 to 10 and the haemoglobin by about 10 g per litre per week, and I would recheck at four weeks." [3][5]

Examiner: "Why does the ferritin, and not the haemoglobin alone, make the diagnosis here?"

"Iron deficiency exists on a spectrum. The stores empty first and lower the ferritin, the transport iron and transferrin saturation fall next, and the haemoglobin drops last. So a child can be iron-deficient and symptomatic with a haemoglobin still in range. The ferritin is the gatekeeper here because a low ferritin in the absence of inflammation confirms iron deficiency unambiguously — his ferritin of 4 micrograms per litre with a normal CRP is diagnostic. The haemoglobin only tells me the severity, not the cause; the ferritin tells me it is iron deficiency rather than thalassaemia trait or anaemia of chronic disease." [1][7]

Examiner: "How would you separate this from thalassaemia trait if the ferritin were equivocal?"

"The Mentzer index is the bedside discriminator — the mean cell volume divided by the red cell count. A value greater than 13 favours iron deficiency, because the red cell count falls; a value less than 13 favours thalassaemia trait, because the red cell count stays high despite the microcytosis. The red cell distribution width helps too — it is raised in iron deficiency and typically normal in thalassaemia trait. If doubt remained, I would check a haemoglobin electrophoresis to confirm thalassaemia trait, because giving iron to a thalassaemia carrier is unhelpful and risks overload over time." [5][4]

Examiner: "Why once daily or alternate day, rather than three times a day?"

"The Stoffel group's randomised trials showed that a single daily dose or alternate-day dosing gives better fractional absorption and fewer gastrointestinal side effects than split three-times-daily dosing. The mechanism is that each iron dose triggers a hepcidin surge from the liver, and hepcidin closes the ferroportin absorption gate. Split dosing keeps hepcidin high all day and limits absorption; once-daily or alternate-day dosing lets hepcidin fall between doses so the next dose is absorbed efficiently. Better absorption plus fewer side effects also improves adherence, which is the commonest reason for treatment failure." [8][3]

Examiner: "At four weeks the haemoglobin has not risen. He says he takes the iron daily. What now?"

"A refractory case at four weeks of confirmed compliant therapy is not a non-responder — it is a missed diagnosis or an ongoing loss. My four questions are: is the adherence genuinely confirmed, is there ongoing blood loss, is there malabsorption, and is the diagnosis correct? I would send coeliac serology with a tissue transglutaminase IgA and a total IgA to exclude IgA deficiency, because coeliac disease is a common and silent cause of refractory iron deficiency. I would look for occult blood loss with a faecal calprotectin and stool studies. And I would reconsider the diagnosis — re-check the red cell indices and, if the ferritin were normal, a haemoglobin electrophoresis for thalassaemia trait. In a child over three years or any boy I would have a low threshold for endoscopic evaluation of the gut for a bleeding source." [1][4]

Examiner: "Explain the hepcidin block to me. Why does a child with Crohn disease have a normal ferritin but a high soluble transferrin receptor?"

"In chronic inflammation, interleukin-6 from the inflamed tissue drives the liver to make hepcidin. Hepcidin binds ferroportin — the iron export channel on enterocytes and macrophages — and causes it to be internalised and degraded, so iron is trapped inside the cells and cannot reach the marrow. The total stores are adequate or even high, so the ferritin is normal or high, but the marrow is genuinely starved and the soluble transferrin receptor rises because it reflects cellular iron need directly and is not an acute-phase reactant. That is functional, or iron-restricted, iron deficiency, and it explains why a normal ferritin in an inflamed child does not exclude iron deficiency and why the soluble transferrin receptor is the discriminating test." [7][1]

Examiner: "What if he had presented with a haemoglobin of 38 and a gallop rhythm?"

"That is severe anaemia with cardiovascular compromise — high-output cardiac failure. Oral iron is too slow. My immediate priority is a cautious, slow packed red cell transfusion given in small aliquots with close monitoring, because the hypoxic, anaemic myocardium is poorly tolerant of volume and at risk of pulmonary oedema. In the very severe case I would consider an exchange transfusion to raise the haemoglobin without the volume load. I transfuse the physiology, not the number — a stable child with a very low haemoglobin is usually managed with iron, sometimes intravenous for speed, rather than transfused. Once he is stabilised the definitive oral regimen and the dietary intervention begin." [3][6]

Examiner: "Why does iron deficiency in infancy matter beyond the haemoglobin?"

"Iron is a cofactor for dopamine synthesis, myelination and energy metabolism in the developing brain, so deficiency in the first two years is associated with impairments in cognition, motor development and behaviour. Some follow-up studies suggest these deficits may persist into adolescence despite correction of the iron deficiency, implying a window of developmental vulnerability. This neurodevelopmental stake — not the haemoglobin number alone — is the reason iron deficiency is treated aggressively and prevented actively in early life, with iron-rich complementary foods from 6 months, iron-fortified formula where formula is used, and screening of high-risk infants." [11][10]

Closing summary

"In summary: iron deficiency anaemia is ferritin first, cause second, iron third, response fourth. This boy has dietary iron deficiency from excessive cow's milk, confirmed by a low ferritin with a normal CRP. I treat with oral elemental iron at 3 to 6 mg per kg per day once daily or alternate day for at least three months, cut the milk and introduce iron-rich solids, and recheck at four weeks for the reticulocyte and haemoglobin response. If it is refractory, I search for adherence, coeliac disease, occult blood loss and the wrong diagnosis. The five never-miss moments are: a refractory case hides a missed diagnosis; never transfuse a stable child for a number alone; never trust a normal ferritin in inflammation; never give iron with cow's milk; and never miss pica. Nail these and you have the spine of every iron deficiency viva." [3][1]