iron deficiency

quick recognition

• fatigue, exercise intolerance, depression, insomnia disproportionate to haemoglobin
• pica (pagophagia = ice craving is classic) — highly specific
• restless leg syndrome — check ferritin in all new presentations
• new ↓ MCV — MCV is stable through life; a new drop is iron deficiency until proven otherwise (other causes: lead, sideroblastic — rare)
• glossitis, angular cheilitis, koilonychia (late signs)

diagnosis / investigations

iron studies — what each marker tells you

interpretation patterns

context-specific diagnostic thresholds

the grey zone — ferritin 30–100 µg/L

• if clinical suspicion persists → therapeutic trial of iron
• BSG recommendation: Hb rise ≥10 g/L within 2–4 weeks → confirms iron deficiency
• sTfR can help if available — elevated in true deficiency, normal in anaemia of chronic disease

gold standard

Bone marrow biopsy with Prussian blue stain — rarely performed in practice. The clinically relevant standard is response to iron repletion (symptoms + Hb + iron studies).

when to suspect — aetiological workup

mandatory investigations

• men and postmenopausal women → bidirectional endoscopy (GI malignancy found in ~11% — lower GI 8.9%, upper GI 2.0%)
• all patients → coeliac serology (tTG-IgA) and H. pylori testing — common treatable causes of malabsorption
• premenopausal women → evaluate for heavy menstrual bleeding first (see below); GI workup if refractory or GI symptoms present

premenopausal women — heavy menstrual bleeding

Iron deficiency prevalence in women: 11–20% (up to 40% in women ≤21 years). Significantly underdiagnosed.

history clues suggesting HMB:

• bleeding >7 days
• clots >2.5 cm (quarter-sized)
• gushing episodes
• overnight accidents
• changing products every 1–2 hours
• adaptive behaviours (double-padding, lifestyle changes)

workup for HMB:

• CBC, coagulation studies (PT, PTT, VWF panel, fibrinogen, platelet aggregation)
• iron studies, TSH, pregnancy test
• pelvic exam ± ultrasound (if structural cause suspected or age ≥40)

when to refer for endoscopy (premenopausal, no GI symptoms):

• iron deficiency persists despite treating HMB
• no identifiable cause of iron deficiency
• personal or family risk factors for GI malignancy
• age ≥40

management

step 1: treat the cause

• GI lesion → endoscopic/surgical management
• HMB → hormonal management + iron repletion concurrently
• coeliac / H. pylori → treat underlying condition
• if iron deficiency persists after HMB treatment → investigate for secondary GI cause

step 2: oral iron

first-line for stable patients who can tolerate oral iron, without malabsorption, active bleeding, or chronic inflammatory disease.

• all formulations are equivalent in efficacy — choose affordable
• dosing: once daily or every other day — alternate-day dosing ↓ GI side effects and shows higher fractional absorption in isotope studies, but RCTs show no significant difference in Hb rise; consider alternate-day when daily dosing not tolerated
• take ≥30 min before meals, 1–2 h before other medications
• avoid concurrent milk, calcium, caffeine, antacids, tea, PPIs
• continue 6–12 months to replenish stores

step 3: IV iron

indications:

• oral iron failure (Hb rise <10 g/L in 2–4 weeks)
• malabsorption (IBD, coeliac, bariatric surgery)
• active bleeding or severe symptomatic anaemia
• chronic/inflammatory disease (CKD, HF, rheumatological)
• 2nd/3rd trimester pregnancy
• IBD (oral iron may be harmful — ↑ luminal inflammation)

• all formulations similar in efficacy
• dose: 1 g empirically or calculate with Ganzoni formula

heart failure — specific evidence

Heart Failure Diagnosis — check ferritin + TSAT in all HF patients.

FAIR-HF (2009), CONFIRM-HF (2015) — IV iron (FCM) in HFrEF with TSAT <20% → improved functional capacity and quality of life. AFFIRM-AHF (2020) — IV FCM at discharge after acute HF → ↓ total HF hospitalisations (RR 0.74), but primary composite endpoint (HF hospitalisations + CV death) not met (p=0.059).

what NOT to do

• do not use a “normal” ferritin to exclude iron deficiency in HF, CKD, or inflammatory disease — ferritin is an acute-phase reactant
• do not check iron studies earlier than 4–6 weeks post-IV iron — earlier values reflect the infusion, not true stores
• do not check iron studies post-transfusion — invalid for several weeks
• do not give IV iron during active bacteraemia — theoretical risk of promoting bacterial growth (iron is a bacterial growth factor)
• do not give epinephrine or antihistamines for Fishbane reactions — unnecessary and may cause adverse effects (see below)
• do not rely on serum iron alone — volatile, diurnal variation, poor discriminatory value
• do not prescribe iron BID/TID routinely — hepcidin surge after first dose blocks subsequent absorption; alternate-day dosing shows equivalent Hb outcomes with fewer side effects

safety and monitoring

oral iron

• GI side effects (nausea, constipation, dark stools) — manage by ↓ frequency or switching formulation
• post-treatment labs at 6 months: target ferritin >30–50 µg/L, TSAT >20%

IV iron — Fishbane reaction

• occurs in ~1% of infusions — not an allergic reaction (not IgE-mediated; no tryptase elevation)
• flushing, arthralgias, myalgias, back/chest pain; no urticaria, angioedema, or bronchospasm
• mechanism: likely related to labile (free) iron
• management: stop infusion → symptoms resolve spontaneously → restart at slower rate → symptoms do not recur

ferric carboxymaltose — 6H syndrome

• develops 1–2 weeks post-infusion: ↑ FGF-23 → renal phosphate wasting → hypophosphataemia, hypovitaminosis D, hypocalcaemia, secondary hyperparathyroidism
• incidence of hypophosphataemia: up to 74% with FCM
• complications: osteomalacia, fractures, muscle weakness, respiratory failure (with repeated dosing)
• monitor serum phosphate after FCM; consider iron derisomaltoside as alternative if recurrent dosing needed

IV iron and infection

• safe in patients with mild, resolving infections
• hold during active bacteraemia
• does not confer higher risk of nosocomial infection in hospitalised patients

special populations

pregnancy

• screen at booking and 24–28 weeks (ferritin <30 µg/L)
• oral iron first-line in 1st trimester; IV iron preferred in 2nd/3rd trimester if oral fails
• perinatal iron deficiency (even without anaemia) may contribute to neurodevelopmental delay — iron is shunted away from the developing brain to maintain haeme synthesis
• check iron parameters each trimester; repeat IV iron if still deficient

CKD

• diagnostic thresholds are higher (see table above) — sensitivity of standard cutoffs remains poor
• many iron-deficient CKD patients are missed
• ESRD on haemodialysis has a different approach (higher ferritin thresholds, routine IV iron protocols) — not covered here

key trials summary