Iron Deficiency Anaemia

Iron deficiency anaemia (IDA) is the commonest anaemia worldwide and the single most repeatedly tested haematology topic in NEET PG. It is a microcytic, hypochromic anaemia caused by depletion of total body iron, with a near-pathognomonic laboratory triad: low serum iron, high TIBC, and low serum ferritin. Master the iron-study pattern, the smear, the management ladder, and Plummer–Vinson syndrome — these four buckets cover almost every question asked.

Iron homeostasis — the background you must know

Total body iron is ~3–4 g (men slightly more). About two-thirds is in haemoglobin, the rest in storage (ferritin, haemosiderin in liver, spleen, marrow) and a small amount in myoglobin and enzymes. Daily losses are tiny (~1 mg, via desquamated cells; menstruating women lose ~2 mg). There is no physiological route to excrete excess iron, so balance is regulated entirely at the level of absorption in the duodenum and upper jejunum.

• Dietary iron exists as haem iron (from haemoglobin/myoglobin in meat — better absorbed) and non-haem iron (plant sources, ferric form, poorly absorbed).
• Non-haem ferric iron (Fe³⁺) is reduced to ferrous (Fe²⁺) by duodenal cytochrome b and gastric acid/vitamin C, taken up by DMT-1 (divalent metal transporter), and exported across the basolateral membrane by ferroportin.
• Hepcidin is the master negative regulator: it degrades ferroportin, blocking iron release from enterocytes and macrophages. Hepcidin is low in IDA (to maximise absorption) and high in anaemia of chronic disease/inflammation.

High-yield: Iron is absorbed in the duodenum as the ferrous (Fe²⁺) form. Vitamin C aids absorption; phytates, tannins (tea), calcium, and antacids/PPIs reduce it.

Etiology — why iron runs out

The causes differ by age, sex, and geography, and the exam loves to map cause to demographic. In adult males and post-menopausal females, IDA is gastrointestinal blood loss until proven otherwise — this is a flagship rule.

Mechanism	Typical causes	Classic exam clue
Chronic blood loss	Menorrhagia, GI bleed (peptic ulcer, colorectal cancer, hookworm, haemorrhoids, NSAID gastropathy), haematuria	Most common cause overall; hookworm (Ancylostoma) common in India
Increased demand	Pregnancy, infancy, adolescence, lactation	Pregnant woman, growing child
Decreased intake	Poor diet, exclusive prolonged breast/cow's-milk feeding in infants	Toddler on excess cow's milk
Malabsorption	Coeliac disease, post-gastrectomy, atrophic gastritis, bariatric surgery, H. pylori	IDA refractory to oral iron → suspect coeliac
Intravascular haemolysis	PNH, mechanical valves, march haemoglobinuria	Urinary iron loss (haemosiderinuria)

High-yield: In an adult male or post-menopausal woman with IDA and no obvious bleeding source, colonoscopy + upper GI endoscopy to exclude occult GI malignancy is mandatory.

Pathophysiology and stages of iron deficiency

Iron deficiency develops in a stepwise sequence, and questions often ask "which is the earliest marker."

1. Iron depletion (negative iron balance) → stores fall → serum ferritin drops first (earliest, most sensitive marker). Marrow iron stores disappear.
2. Iron-deficient erythropoiesis → serum iron falls, TIBC rises, transferrin saturation falls, and soluble transferrin receptor (sTfR) rises. RBCs still normocytic-normochromic early.
3. Iron deficiency anaemia → haemoglobin falls, cells become microcytic and hypochromic (low MCV, low MCH, low MCHC), RDW rises.

High-yield: Serum ferritin is the first lab parameter to fall and the best single test for iron stores. A low ferritin is diagnostic of IDA; however ferritin is an acute-phase reactant, so it can be falsely normal/high in infection, inflammation, liver disease, or malignancy.

Clinical features

General anaemia symptoms: fatigue, exertional dyspnoea, palpitations, pallor (best seen in conjunctiva, nail bed, palmar creases), tachycardia, and in severe cases high-output failure / flow murmurs.

Features specific to iron deficiency (tissue iron depletion):

• Koilonychia (spoon-shaped nails)
• Angular stomatitis / cheilosis and glossitis (smooth, atrophic, sore tongue)
• Pica — craving for non-food items; pagophagia (ice craving) is highly specific for IDA
• Dysphagia from a post-cricoid oesophageal web → Plummer–Vinson syndrome
• Restless legs syndrome, hair loss, poor cognition/exercise capacity
• In children: irritability, impaired psychomotor and cognitive development, breath-holding spells, blue sclera

High-yield: Pagophagia (ice pica) and koilonychia are the most exam-favoured specific signs. Blue sclera and restless legs are increasingly asked.

Plummer–Vinson syndrome (Paterson–Brown–Kelly syndrome)

A classic eponymous triad — guaranteed value.

High-yield: Plummer–Vinson = Iron deficiency anaemia + Dysphagia (upper oesophageal web) + Glossitis. Typically middle-aged women. It is a premalignant condition predisposing to post-cricoid / upper oesophageal squamous cell carcinoma. Webs respond to iron therapy ± dilatation.

Mnemonic — "Plummer's GAD": Glossitis, Anaemia (iron deficiency), Dysphagia.

Diagnosis and investigation of choice

The diagnostic backbone is the complete blood count + peripheral smear + iron studies, with ferritin as the cornerstone.

Iron-study pattern (the single most tested table)

Parameter	IDA	Anaemia of chronic disease	Thalassaemia trait	Sideroblastic anaemia
Serum iron	↓	↓	Normal/↑	↑
TIBC / transferrin	↑	↓	Normal	Normal/↓
Transferrin saturation	↓ (<15–16%)	↓ (usually >15%)	Normal/↑	↑
Serum ferritin	↓ (<15–30 µg/L)	Normal/↑	Normal/↑	↑
sTfR	↑	Normal	Normal/↑	Normal
Marrow iron stores	Absent	Present (increased)	Present	Ring sideroblasts

High-yield: The defining IDA triad is low serum iron + HIGH TIBC + low ferritin with transferrin saturation <15%. This high TIBC is the key feature that separates IDA from anaemia of chronic disease (where TIBC is low).

Cut-off values worth memorising: serum ferritin <15 µg/L is highly specific for absent iron stores (<30 µg/L commonly used clinically; <100 µg/L may indicate deficiency in chronic inflammation/CKD/CHF). Transferrin saturation <16% indicates iron-deficient erythropoiesis.

Peripheral blood smear

• Microcytic, hypochromic red cells (increased central pallor)
• Anisocytosis (variable size) and poikilocytosis (variable shape) → reflected as high RDW (RDW is normal in thalassaemia — a key discriminator)
• Pencil cells (elliptocytes/cigar cells) and target cells
• Reactive thrombocytosis is common
• Reticulocyte count is low/inappropriately normal for the degree of anaemia

High-yield: Pencil cells + high RDW + thrombocytosis on smear point to IDA. In β-thalassaemia trait RDW is normal, target cells and basophilic stippling are prominent, and RBC count is paradoxically high/normal with disproportionately low MCV.

Distinguishing IDA from thalassaemia trait — discriminant indices

• Mentzer index = MCV / RBC count. >13 → IDA; <13 → thalassaemia trait.
• IDA: low RBC count, high RDW, low ferritin. Thalassaemia trait: high/normal RBC count, normal RDW, normal ferritin, raised HbA₂ on electrophoresis.

Bone marrow

Marrow aspirate with Perls' (Prussian blue) stain showing absent stainable iron is the gold standard for iron deficiency — but rarely needed because ferritin suffices. The flow of confirming diagnosis: CBC (low MCV/Hb) → smear (hypochromic microcytic, pencil cells) → iron studies (↓ferritin, ↑TIBC, ↓Tsat) → identify and treat the cause.

Management — the treatment sequence

Treat the anaemia and the underlying cause. The therapeutic ladder is: oral iron → IV iron (if oral fails/contraindicated) → transfusion (only if haemodynamically significant).

1. Oral iron — first line and drug of choice

Ferrous sulphate is the drug of choice: 325 mg tablet provides ~65 mg elemental iron; usual dose 100–200 mg elemental iron/day. Best taken on an empty stomach with vitamin C (orange juice); avoid with tea, milk, antacids, PPIs.

High-yield: Expected response to oral iron — reticulocytosis peaks at day 5–10; haemoglobin rises by ~1 g/dL every 1–2 weeks (≈2 g/dL over 3 weeks). Continue iron for 3–6 months after haemoglobin normalises to replenish stores.

Recent evidence favours alternate-day or once-daily dosing over divided multiple daily doses — lower doses transiently suppress hepcidin and improve fractional absorption while reducing GI side-effects.

Side-effects: nausea, epigastric pain, constipation, black stools (harmless — must not be mistaken for melaena). GI intolerance is the main cause of non-adherence.

2. Causes of failure to respond to oral iron

Remember the differential when Hb does not rise — frequently examined:

• Wrong diagnosis (thalassaemia, ACD, sideroblastic)
• Non-compliance / intolerance
• Continued blood loss exceeding intake
• Malabsorption (coeliac disease, atrophic gastritis, H. pylori, post-bariatric)
• Concurrent deficiency (B12/folate) or inflammation

3. Parenteral (IV) iron — indications

Formulations: ferric carboxymaltose, iron sucrose, ferric derisomaltose, low-molecular-weight iron dextran. IV avoids the GI tract entirely.

High-yield: Indications for IV iron — intolerance/failure of oral iron, ongoing blood loss > absorption, malabsorption (coeliac, post-gastrectomy), chronic kidney disease on erythropoietin/dialysis, inflammatory bowel disease, second/third-trimester pregnancy needing rapid repletion, and need for rapid replenishment before surgery.

IM iron (Z-track technique to avoid skin staining) is largely obsolete. Anaphylaxis risk is highest with high-molecular-weight dextran (no longer used).

4. Blood transfusion — last resort

Reserved for haemodynamic compromise, symptomatic severe anaemia, active major bleeding, or cardiac decompensation — not for the number alone. A common restrictive threshold is Hb <7 g/dL (consider <8 g/dL in cardiac disease/perioperative). Transfusion corrects oxygen-carrying capacity but does not treat the cause.

Stepwise approach: Confirm IDA → start ferrous sulphate 100–200 mg elemental/day → check reticulocytes day 7–10 and Hb at 3–4 weeks → if responding, continue 3–6 months → if not responding, recheck compliance, exclude malabsorption/ongoing loss/wrong diagnosis → escalate to IV iron → transfuse only if haemodynamically unstable.

Complications

• High-output cardiac failure in severe chronic anaemia
• Plummer–Vinson syndrome → post-cricoid SCC (premalignant)
• Impaired neurocognitive development in children, low birth weight / preterm birth in maternal IDA
• Worsened outcomes in heart failure and CKD
• Pica-related complications (lead ingestion, dental damage)

Key differentials (the microcytic anaemia approach)

Microcytic anaemia (low MCV) differential — mnemonic "TAILS": Thalassaemia, Anaemia of chronic disease (can be normocytic too), Iron deficiency, Lead poisoning / Lead, Sideroblastic anaemia.

Feature	IDA	Thalassaemia trait	ACD	Sideroblastic	Lead poisoning
Ferritin	↓	Normal/↑	Normal/↑	↑	Normal/↑
TIBC	↑	Normal	↓	Normal	Normal
RDW	↑	Normal	Normal	↑ (dimorphic)	Normal/↑
RBC count	↓	High/normal	↓/normal	↓	↓
Distinctive clue	Pencil cells, pica	High HbA₂, target cells	Underlying chronic illness	Ring sideroblasts	Basophilic stippling, burton's line

High-yield: Basophilic stippling can occur in both IDA and lead poisoning/thalassaemia, but coarse basophilic stippling + neuropsychiatric features + a child with developmental delay points to lead poisoning (also a sideroblastic-type picture).

Recently asked / exam angle

• "Earliest lab change in iron deficiency?" → Serum ferritin falls first.
• "Iron study pattern in IDA?" → ↓iron, ↑TIBC, ↓ferritin, ↓transferrin saturation (<15%). Contrast with ACD (↓TIBC).
• Mentzer index >13 = IDA; <13 = thalassaemia trait — repeatedly tested as a calculation/discriminator.
• Specific pica = pagophagia (ice); koilonychia, blue sclera, restless legs as IDA-specific signs.
• Plummer–Vinson triad and its premalignant (post-cricoid SCC) nature.
• Site/form of iron absorption = duodenum, ferrous (Fe²⁺), enhanced by vitamin C, regulated by hepcidin (low in IDA).
• Expected reticulocyte response to oral iron at day 5–10 and Hb rise ~1 g/dL per 1–2 weeks; continue iron 3–6 months after Hb normalises.
• Indications for IV iron (CKD on EPO, malabsorption, intolerance, ongoing loss).
• Adult male/post-menopausal IDA → evaluate GI tract (endoscopy/colonoscopy) for occult malignancy.
• Smear features: pencil cells, anisopoikilocytosis, high RDW, reactive thrombocytosis.
• Hepcidin physiology — low in IDA, high in ACD; the molecular reason ACD has reduced iron availability.

Rapid revision

1. IDA = microcytic hypochromic anaemia; commonest anaemia worldwide; most common cause = chronic blood loss.
2. Iron absorbed in duodenum as Fe²⁺; vitamin C ↑, tea/phytates/PPIs ↓ absorption.
3. Serum ferritin falls first and is the best single marker of iron stores; it is an acute-phase reactant (falsely raised in inflammation).
4. Diagnostic triad: ↓serum iron, ↑TIBC, ↓ferritin, transferrin saturation <15%.
5. Smear: hypochromic microcytic cells, pencil cells, anisopoikilocytosis, high RDW, thrombocytosis.
6. Mentzer index = MCV/RBC; >13 IDA, <13 thalassaemia trait. Thalassaemia has normal RDW, high RBC, raised HbA₂.
7. Specific signs: koilonychia, pagophagia (ice pica), glossitis, angular stomatitis, blue sclera, restless legs.
8. Plummer–Vinson = IDA + oesophageal web (dysphagia) + glossitis; premalignant for post-cricoid SCC.
9. Drug of choice = oral ferrous sulphate (~65 mg elemental iron/325 mg tablet); causes black stools.
10. Response: reticulocytosis day 5–10, Hb ↑ ~1 g/dL/1–2 weeks; continue iron 3–6 months after Hb normalises.
11. IV iron for intolerance/failure, malabsorption, CKD on EPO, ongoing loss; transfuse only if haemodynamically unstable / Hb <7 g/dL.
12. Gold standard = absent marrow iron on Perls' stain; adult male/post-menopausal IDA mandates GI evaluation for occult cancer.