Microcytic Anemia (Iron Deficiency, ACD, Thal Trait)

📋 Key Information Summary

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Microcytic anaemia (MCV <80 fL) in adults is most commonly caused by iron deficiency anaemia (IDA), anaemia of chronic disease (ACD), or thalassaemia trait — distinguishing these is the first priority.
A serum ferritin <30 µg/L is highly specific for iron deficiency in most adults; in the presence of inflammation (elevated CRP), a ferritin <100 µg/L should raise suspicion for concurrent iron deficiency.
Transferrin saturation (TSAT) <20% supports iron deficiency; in ACD, TSAT may be low-normal (15–20%) but ferritin is typically normal or elevated.
In men and postmenopausal women with unexplained iron deficiency, GI blood loss must be assumed until proven otherwise — pursue upper and lower endoscopy as indicated.
A trial of oral iron (ferrous sulfate 325 mg PO daily for 4–6 weeks with reticulocyte response) is both diagnostic and therapeutic when the cause is uncertain.
Thalassaemia trait (α or β) is common in Australians of Southeast Asian, Mediterranean, Middle Eastern, and Indian subcontinent descent — an MCV <80 fL with normal iron studies and a raised RBC count should prompt haemoglobin electrophoresis or HPLC.
First-line oral iron is ferrous sulfate 325 mg (≈105 mg elemental iron) once daily on an empty stomach; alternate-day dosing may improve fractional absorption and tolerability.
IV iron (ferric carboxymaltose or iron polymaltose) is indicated when oral iron is not tolerated, malabsorption is present, or rapid correction is needed — available under PBS Authority Required.
Referral to haematology is warranted for unexplained refractory anaemia, suspected thalassaemia intermedia/major, or complex combined deficiency syndromes.
Referral to gastroenterology is indicated for suspected GI malignancy, coeliac disease screening, or failure to respond to adequate oral iron replacement.
Aboriginal and Torres Strait Islander Australians have disproportionately higher rates of IDA due to remote access barriers, dietary factors, chronic infection, and hookworm — active screening and community-based supplementation are essential.
Chronic kidney disease, chronic inflammatory conditions, and heavy menstrual bleeding are the most prevalent contributors to IDA in Australian general practice.

Introduction & Australian Epidemiology

Microcytic anaemia — defined as a haemoglobin below the reference range with a mean corpuscular volume (MCV) less than 80 femtolitres (fL) — is one of the most common laboratory findings in Australian general practice. The differential diagnosis is anchored by three principal aetiologies: iron deficiency anaemia (IDA), anaemia of chronic disease (ACD), and thalassaemia trait (α or β). Accurate differentiation is essential because the management pathways diverge significantly.

Iron deficiency is the most common nutritional deficiency worldwide and the leading cause of anaemia in Australia. The Australian Bureau of Statistics (ABS) National Health Survey estimates that approximately 8% of Australian adults have some degree of iron deficiency, with higher prevalence in women of reproductive age (up to 15–20%), pregnant women, young children, and older adults. The Australian Institute of Health and Welfare (AIHW) reports that iron deficiency anaemia accounts for a substantial proportion of preventable hospitalisations each year.

Thalassaemia trait is particularly relevant in Australia's multicultural population. β-thalassaemia trait prevalence ranges from 1–3% in Australians of Greek, Italian, Cypriot, and Lebanese descent, and up to 5–8% in some Southeast Asian communities. α-thalassaemia trait is common in people of Chinese, Vietnamese, Filipino, and Aboriginal and Torres Strait Islander background. Screening in pregnancy and pre-conception is recommended by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG).

Anaemia of chronic disease is the second most common cause of anaemia globally and is frequently encountered in Australian patients with chronic kidney disease (CKD), rheumatoid arthritis, inflammatory bowel disease (IBD), chronic infections, and malignancy. ACD often coexists with true iron deficiency, creating a mixed picture that demands careful laboratory interpretation.

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Clinical pearl: Up to 30% of patients with microcytic anaemia have a dual pathology — most commonly ACD with concurrent iron deficiency. A single low ferritin in the setting of inflammation does not exclude iron deficiency; conversely, a normal or high ferritin in the setting of chronic disease does not exclude iron depletion. Always interpret iron studies in the clinical context.

Pathophysiology — Differentiating IDA, ACD, and Thalassaemia Trait

Understanding the underlying mechanism of each cause of microcytic anaemia is essential for accurate diagnosis and targeted management.

Iron Deficiency Anaemia (IDA)

Iron is essential for haemoglobin synthesis. Iron deficiency develops through three mechanisms: increased demand (pregnancy, growth), decreased intake (poor diet, malabsorption — coeliac disease, bariatric surgery, achlorhydria), or increased loss (menstruation, GI bleeding, chronic haemoglobinuria). Iron stores are progressively depleted: first serum ferritin falls, then serum iron drops with rising total iron-binding capacity (TIBC), and finally haemoglobin synthesis fails, producing microcytic, hypochromic red cells. The RDW (red cell distribution width) is typically elevated, reflecting anisocytosis from a mixed population of iron-deficient and older normocytic cells.

Anaemia of Chronic Disease (ACD)

ACD is mediated by inflammatory cytokines — principally interleukin-6 (IL-6) — which stimulate hepatic production of hepcidin. Hepcidin blocks ferroportin on enterocytes and macrophages, trapping iron in storage sites and reducing serum iron availability. The result is a functional iron deficiency: iron is present in the body but is not accessible for erythropoiesis. Ferritin, an acute-phase reactant, is normal or elevated. TIBC is low or normal (contrast with IDA where TIBC is elevated). The MCV is usually low-normal or mildly low (75–85 fL), but can be frankly microcytic in longstanding disease.

Thalassaemia Trait (α and β)

Thalassaemia trait results from reduced synthesis of one or more globin chains of haemoglobin. In β-thalassaemia trait, there is reduced β-globin production leading to an imbalance of α:β chains, ineffective erythropoiesis, and microcytosis. The hallmark is disproportionate microcytosis relative to the degree of anaemia: the MCV is often very low (55–70 fL) but the haemoglobin may be only mildly reduced or even normal. The RBC count is paradoxically elevated (often >5.0 × 10¹²/L), which is the opposite of IDA. Iron studies are characteristically normal. α-thalassaemia trait (single or double gene deletion) produces a similar but often milder picture. Haemoglobin electrophoresis or HPLC confirms β-thalassaemia trait by demonstrating an elevated HbA₂ (>3.5%); α-thalassaemia trait requires genetic testing for confirmation.

Feature	Iron Deficiency Anaemia	Anaemia of Chronic Disease	β-Thalassaemia Trait
MCV	Low (60–79 fL)	Low-normal to low (75–85 fL)	Very low (55–70 fL)
RBC count	Low or low-normal	Low or low-normal	Normal or elevated (>5.0)
RDW	Elevated (>14.5%)	Normal or mildly elevated	Normal (<14.5%)
Ferritin	Low (<30 µg/L)	Normal or elevated	Normal
Serum iron	Low	Low or low-normal	Normal
TIBC	High (>70 µmol/L)	Low or normal	Normal
TSAT	Low (<16%)	Low-normal (15–20%)	Normal (20–50%)
Peripheral smear	Hypochromia, pencil cells, target cells	Normochromic or mildly hypochromic	Target cells, basophilic stippling
Key test	Ferritin; trial of iron	CRP/ESR; hepcidin (research)	Hb electrophoresis/HPLC (HbA₂ >3.5%)

Initial Classification — Confirming Anaemia and Microcytosis

The evaluation of microcytic anaemia begins with establishing that the patient is genuinely anaemic (haemoglobin below the sex- and age-adjusted reference range) and that the MCV is below 80 fL. In Australia, the following adult haemoglobin reference ranges apply:

Population	Normal Haemoglobin (g/L)	Anaemia Threshold (g/L)
Adult males	130–180	<130
Adult females (non-pregnant)	120–160	<120
Pregnant females	110–150	<110
Children (varies by age)	Age-dependent	See paediatric reference

Systematic History in Microcytic Anaemia

A thorough history is the single most important step in narrowing the differential. The following domains should be systematically assessed:

Dietary history: Vegan or vegetarian diet, restrictive eating patterns, limited red meat intake, excessive tea or coffee with meals (inhibits non-haem iron absorption).
Menstrual and obstetric history: Heavy menstrual bleeding (HMB) — defined as >80 mL blood loss per cycle or lasting >7 days — is the most common cause of IDA in premenopausal Australian women. Gravidity, parity, history of postpartum haemorrhage, intermenstrual bleeding, and recent pregnancy.
Gastrointestinal symptoms: Dyspepsia, altered bowel habit, rectal bleeding, melaena, abdominal pain, dysphagia, weight loss. These symptoms raise the suspicion for GI malignancy, peptic ulcer disease, inflammatory bowel disease, or coeliac disease.
Medication history: NSAIDs (including over-the-counter ibuprofen and aspirin), anticoagulants, antiplatelet agents, proton pump inhibitors (may impair iron absorption), oral contraceptives (effect on menstrual loss).
Family history: Thalassaemia trait, haemoglobinopathy, iron overload (haemochromatosis), hereditary spherocytosis, or other haematological conditions. Ethnicity is relevant — Southeast Asian, Mediterranean, Middle Eastern, Indian subcontinent, and African heritage all confer higher risk of thalassaemia.
Chronic disease history: CKD, rheumatoid arthritis, inflammatory bowel disease, chronic infections (including HIV, tuberculosis, helminths), malignancy, chronic heart failure.
Surgical history: Bariatric surgery (gastric bypass, sleeve gastrectomy), gastrectomy, small bowel resection — all predispose to malabsorption of iron.
Donation history: Frequent blood donation (Red Cross Lifeblood allows donation every 12 weeks for males, every 16 weeks for females) can deplete iron stores over time.

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Red flags demanding urgent evaluation: Unintentional weight loss, progressive dysphagia, change in bowel habit in a patient >50 years, melaena, haematochezia, iron deficiency in a male or postmenopausal woman without an obvious cause, or haemoglobin <80 g/L with haemodynamic compromise. These warrant same-day or next-day referral.

Baseline Laboratory Investigations

Once microcytic anaemia is confirmed, a focused panel of investigations should be requested to characterise the aetiology. The following tests form the initial workup:

Essential Full Blood Count (FBC/CBC) with indices Haemoglobin, MCV, MCH, MCHC, RDW, RBC count, platelet count, WCC. MCV <80 fL confirms microcytosis. Elevated RDW suggests mixed population (IDA). Normal RDW with very low MCV and high RBC count raises suspicion for thalassaemia trait.

Essential Reticulocyte Count (absolute) Assesses marrow response. Low or inappropriately normal reticulocyte count in the setting of anaemia suggests hypoproliferative process (iron deficiency, ACD). Elevated reticulocytes suggest haemolysis or blood loss. MBS item 65120.

Essential Iron Studies — Serum Iron, TIBC, Transferrin Saturation (TSAT) Serum iron (reference 10–30 µmol/L), TIBC (reference 45–70 µmol/L), TSAT = (iron ÷ TIBC) × 100. In IDA: low iron, high TIBC, TSAT <16%. In ACD: low/normal iron, low/normal TIBC, TSAT 15–20%. MBS item 66549.

Essential Serum Ferritin The single most useful test for iron stores. Ferritin <30 µg/L is diagnostic of depleted iron stores. In the absence of inflammation, ferritin <15 µg/L is virtually diagnostic of iron deficiency. In patients with concurrent inflammation (CRP elevated), ferritin <100 µg/L is suggestive of iron deficiency. MBS item 66549.

Available CRP and/or ESR Elevated CRP (>5 mg/L) or ESR signals inflammation and raises the possibility of ACD. Essential for correct interpretation of ferritin. Also helps identify chronic infection or occult malignancy. MBS item 66535.

Available Peripheral Blood Film Direct visualisation of red cell morphology: hypochromia, microcytosis, pencil cells (IDA); target cells and basophilic stippling (thalassaemia); rouleaux formation (inflammation); schistocytes (microangiopathy). MBS item 65075.

Available Haemoglobin Electrophoresis / HPLC If thalassaemia trait is suspected (MCV very low, normal iron studies, elevated RBC count, family history, relevant ethnicity). β-thalassaemia trait confirmed by HbA₂ >3.5%. α-thalassaemia trait requires genetic testing (HbH inclusion bodies may be seen on special stain). MBS item 66588.

Available Coeliac Serology (anti-tTG IgA ± total IgA) Iron malabsorption from coeliac disease is an under-recognised cause of IDA in Australian adults. Recommended if IDA is unexplained, or if GI symptoms, family history, or associated autoimmune conditions are present. MBS item 66822.

Available Renal Function (eGFR, Creatinine, Urea) CKD is a common cause of ACD and contributes to anaemia through reduced erythropoietin production and chronic inflammation. Essential baseline in all patients with microcytic anaemia.

Available Soluble Transferrin Receptor (sTfR) Available through specialist pathology request. Elevated in true iron deficiency, normal in ACD. The sTfR/log ferritin ratio (>2 suggests IDA, <1 suggests ACD) helps differentiate mixed aetiology. Not routinely PBS-funded but available through major Australian laboratories (Sullivan Nicolaides, Douglass Hanly Moir, Melbourne Pathology).

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Important: Always request CRP alongside iron studies. Ferritin is an acute-phase reactant — in the presence of inflammation (infection, malignancy, autoimmune disease), ferritin may be "falsely normal" or even elevated despite depleted iron stores. A ferritin of 45 µg/L with a CRP of 80 mg/L does NOT exclude iron deficiency.

Diagnosing Iron Deficiency

Iron deficiency exists on a spectrum: iron depletion (reduced stores but no functional deficit), iron-deficient erythropoiesis (stores exhausted, erythropoiesis impaired but haemoglobin not yet below threshold), and iron deficiency anaemia (frank anaemia with depleted stores). Identifying iron deficiency at any stage allows early intervention.

Diagnostic Criteria

The diagnosis of iron deficiency is established by the following laboratory findings:

Parameter	Iron Deficiency	ACD (without ID)	ACD + ID (mixed)
Ferritin	<30 µg/L (<100 if CRP elevated)	Normal to elevated	30–100 µg/L with elevated CRP
TSAT	<16%	15–20%	<20%
TIBC	Elevated (>70 µmol/L)	Low to normal	Variable
sTfR	Elevated	Normal	Elevated
sTfR/log ferritin ratio	>2	<1	1–2

The Trial of Iron

When laboratory results are equivocal (e.g., ferritin 15–30 µg/L with borderline indices), a therapeutic trial of oral iron serves both a diagnostic and therapeutic purpose:

Prescribe ferrous sulfate 325 mg once daily (equivalent to ~105 mg elemental iron) for 4–6 weeks.
Check a reticulocyte count at 1–2 weeks — a rise in reticulocytes (>2% absolute increase or peak reticulocyte haemoglobin content rise) confirms iron-responsive erythropoiesis.
Repeat FBC at 4–6 weeks — a haemoglobin rise of ≥10 g/L strongly supports the diagnosis of IDA.
If no response is seen, assess adherence, consider malabsorption, and evaluate for alternative diagnoses (ACD, thalassaemia trait, combined pathology).

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Tip for improved absorption: Emerging evidence suggests that alternate-day dosing of oral iron (e.g., ferrous sulfate 325 mg every other day) may result in equal or superior fractional absorption compared with daily dosing, with fewer GI side effects (stool colour change, nausea, constipation). This is supported by a randomised controlled trial published in The Lancet Haematology (Stoffel et al., 2017) and endorsed by several Australian haematologists.

Differentiating IDA from Thalassaemia Trait

Several simple indices can help distinguish β-thalassaemia trait from IDA before confirmatory testing:

Index	Formula	IDA	β-Thal Trait
Mentzer Index	MCV ÷ RBC	>13	<13
England-Fraser	MCV − (5 × Hb) − RBC − 3.4	>0	<0
RDW	—	Elevated (>14.5%)	Normal (<14.5%)

These indices are screening tools only. Definitive diagnosis of thalassaemia trait requires haemoglobin electrophoresis/HPLC (for β-thal) or genetic testing (for α-thal).

Search for Blood Loss

Once iron deficiency is confirmed, the critical next step is identifying the cause of iron loss. In premenopausal women, menstrual blood loss is the most common explanation and can often be accepted as the cause after a thorough menstrual history. However, in men, postmenopausal women, and premenopausal women with severe or refractory IDA, GI blood loss must be actively sought.

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Critical rule: In any male or postmenopausal female with confirmed iron deficiency anaemia, gastrointestinal malignancy must be excluded. Colorectal cancer is the second most common cause of cancer-related death in Australia (Australian Institute of Health and Welfare), and iron deficiency may be the earliest — and only — presenting sign.

Evaluation Pathway for GI Blood Loss

1

Faecal Occult Blood Test (FOBT) / Faecal Immunochemical Test (FIT)

The quantitative FIT is preferred over traditional guaiac-based FOBT for its higher sensitivity for lower GI bleeding. A positive FIT in the context of IDA mandates colonoscopy. However, a negative FIT does not exclude GI malignancy or significant blood loss — sensitivity for colorectal cancer is approximately 70–80% per single sample. If clinical suspicion remains, proceed to endoscopy regardless of FIT result.

2

Colonoscopy

Recommended for all men and postmenopausal women with unexplained IDA, and for any patient with a positive FIT. Colonoscopy allows direct visualisation and biopsy of the colon and terminal ileum. It identifies colorectal carcinoma, colonic angiodysplasia, inflammatory bowel disease, and colonic polyps. Per the Clinical Practice Guidelines for Colorectal Cancer Screening (NHMRC/RACGP), patients >50 years should be considered for colonoscopy even if FIT-negative when iron deficiency is unexplained.

3

Upper GI Endoscopy (OGD / Gastroscopy)

Indicated for unexplained IDA, particularly with upper GI symptoms (dyspepsia, dysphagia, epigastric pain, nausea/vomiting). Identifies peptic ulcers, erosive oesophagitis, gastric/oesophageal malignancy, coeliac disease (duodenal biopsy), and gastric angiodysplasia. Coeliac disease should be screened with anti-tTG IgA prior to endoscopy — duodenal biopsy with villous atrophy confirms the diagnosis.

4

Capsule Endoscopy / CT Enterography

If bidirectional endoscopy is negative and IDA persists, small bowel evaluation should be considered. Video capsule endoscopy (VCE) is the preferred non-invasive method for identifying small bowel angiodysplasia, Crohn's disease, or small bowel tumours. CT enterography provides complementary cross-sectional information. These investigations are typically arranged through gastroenterology referral.

Non-GI Causes of Iron Loss

Heavy menstrual bleeding (HMB): The most common cause in premenopausal women. Structured assessment using a pictorial blood loss assessment chart (PBAC) or menstrual diary may be helpful. Pelvic ultrasound to exclude structural causes (fibroids, polyps, adenomyosis).
Chronic haemoglobinuria/haemosiderinuria: Consider in rare causes — paroxysmal nocturnal haemoglobinuria (PNH), mechanical heart valves, chronic intravascular haemolysis. Urine dipstick positive for blood with no RBCs on microscopy is a clue.
Frequent blood donation: Each whole-blood donation removes approximately 200–250 mg of iron. Red Cross Lifeblood checks haemoglobin pre-donation but does not routinely assess ferritin.
Genitourinary losses: Haematuria (bladder/renal malignancy, glomerulonephritis), epistaxis (hereditary haemorrhagic telangiectasia).

When to Refer to Haematology or Gastroenterology

Most cases of microcytic anaemia can be managed in primary care. However, specific clinical scenarios warrant specialist referral:

Referral to Haematology

Indication	Urgency	Rationale
Unexplained iron deficiency after full workup	Semi-urgent (2–4 weeks)	Specialist evaluation may identify occult causes (PNH, myelodysplasia, rare haemoglobinopathy)
Confirmed thalassaemia with Hb <100 g/L or symptomatic	Semi-urgent	May represent thalassaemia intermedia requiring specialist monitoring
Suspected thalassaemia major or compound heterozygote	Urgent	Requires transfusion planning, genetic counselling, and long-term specialist follow-up
Severe anaemia (Hb <70 g/L) or haemodynamic instability	Immediate (ED)	May require packed red blood cell transfusion, IV iron, and inpatient management
Failure to respond to 4–6 weeks of adequate oral iron	Routine (4–6 weeks)	Need to assess for malabsorption, non-adherence, ongoing loss, or alternative diagnosis
Need for IV iron — intolerance or contraindication to oral	Routine	IV iron (ferric carboxymaltose, iron polymaltose) can be administered in haematology day units or some GP practices with appropriate anaphylaxis management

Referral to Gastroenterology

Indication	Urgency	Rationale
IDA in a male or postmenopausal female without obvious cause	Urgent (2 weeks)	National Safety and Quality Health Service (NSQHS) Standards mandate timely investigation for suspected GI malignancy
Positive FIT with IDA	Urgent	Colonoscopy within 30 days per National Bowel Cancer Screening Program pathways
Suspected coeliac disease (positive serology + IDA)	Semi-urgent	Duodenal biopsy required for definitive diagnosis; ongoing malabsorption without diagnosis leads to refractory IDA
Persistent GI symptoms (dyspepsia, dysphagia, rectal bleeding)	Semi-urgent	Direct visualisation and biopsy to exclude peptic ulcer disease, oesophageal/gastric malignancy, Barrett's oesophagus, or IBD
Negative bidirectional endoscopy with persistent IDA	Routine	Capsule endoscopy or CT enterography for small bowel evaluation

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Two-week wait referral: In most Australian states and territories, a structured "2-week wait" or "rapid access" referral pathway exists for suspected GI malignancy. Use your state's designated referral form (e.g., NSW Cancer Institute urgent referral template, Victoria's Optimal Care Pathway). Include clinical urgency, relevant history, and all iron study results.

Treatment — Iron Replacement Therapy

Treatment of IDA involves correcting the underlying cause of iron loss AND replenishing iron stores. Both are essential — iron replacement without identifying the cause may mask a sinister pathology, while treating the cause without replacing iron leaves the patient symptomatic for months.

Oral Iron Replacement

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Ferrous Sulfate

Ferro-Gradumet® · Ferro-Grad C® · Generic · First-line oral iron

Adult dose 325 mg (= 105 mg elemental iron) PO once daily, ideally on an empty stomach. Alternate-day dosing is an acceptable alternative for improved tolerability and may enhance fractional absorption.

Paediatric dose 3 mg/kg/day elemental iron PO once daily (e.g., ferrous sulfate liquid 5 mg/kg/day). Maximum 100 mg elemental iron daily in children.

Duration Continue for 3 months after haemoglobin normalisation to replenish iron stores (ferritin target >100 µg/L). Total treatment typically 4–6 months.

Renal adjustment No dose adjustment required.

Hepatic adjustment No dose adjustment required. Avoid in haemochromatosis.

PBS status ✔ PBS General Benefit

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Ferrous Fumarate

Ferro-F® · Generic · Alternative oral iron

Adult dose 325 mg (= 107 mg elemental iron) PO once daily. Slightly better tolerated than ferrous sulfate in some patients.

Paediatric dose As for ferrous sulfate — 3 mg/kg/day elemental iron.

PBS status ✔ PBS General Benefit

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Iron Polymaltose (oral)

Maltofer® · Ferric hydroxide polymaltose complex · Better tolerated

Adult dose 100–200 mg elemental iron PO daily in divided doses (tablets or liquid).

Note Ferric (Fe³⁺) form — does not require gastric acid for absorption; may be better tolerated with fewer GI side effects. Evidence suggests slightly lower efficacy than ferrous salts but improved compliance.

PBS status ✔ PBS General Benefit

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Absorption tips: Take oral iron on an empty stomach with vitamin C (ascorbic acid 200 mg or orange juice) to enhance absorption. Avoid concurrent intake with tea, coffee, calcium supplements, antacids, and proton pump inhibitors, which all reduce absorption. If GI side effects (nausea, constipation, epigastric discomfort) limit tolerability, switch to alternate-day dosing or iron polymaltose (Maltofer).

Intravenous Iron Therapy

IV iron is indicated when:

Oral iron is not tolerated (persistent GI side effects despite alternate-day dosing and formulation changes)
Malabsorption is present (coeliac disease, IBD, post-bariatric surgery, achlorhydria)
Rapid correction is required (pre-surgery, late pregnancy, severe symptomatic anaemia)
Ongoing losses exceed oral replacement capacity (chronic GI bleeding requiring procedural intervention, heavy menses awaiting treatment)
CKD patients on erythropoiesis-stimulating agents (ESA) who require additional iron

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Ferric Carboxymaltose

Ferinject® · High-dose single-infusion IV iron

Adult dose Total iron deficit calculated by Ganzoni formula or simplified: 500–1000 mg IV infusion over 15 minutes. Repeat at 1-week intervals if >1000 mg total dose required. Maximum 1000 mg per infusion.

Ganzoni formula Total iron deficit (mg) = body weight (kg) × (target Hb − actual Hb) (g/L) × 0.24 + 500 mg (store iron)

Key adverse effects Hypophosphataemia (transient, usually clinically insignificant; rarely severe with prolonged use), injection site reactions, nausea, headache. Anaphylaxis is rare (<1:200,000).

Renal adjustment No dose adjustment. Safe in CKD stages 3–5 (not on dialysis).

PBS status ⚠ PBS Authority Required — for documented intolerance to oral iron, malabsorption, chronic kidney disease, or pregnancy (≥2nd trimester).

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Iron Polymaltose (IV)

Ferrum H® · Iron polymaltose complex · Traditional IV iron

Adult dose Total dose infusion (TDI) of up to 1500 mg diluted in 500 mL NaCl 0.9%, infused over 4–6 hours. Alternatively, divided doses of 200–500 mg per session.

Key adverse effects Arthralgia, myalgia, flushing (dose-related). Anaphylactoid reactions are rare but anaphylaxis management must be available. Phlebitis at infusion site.

PBS status ⚠ PBS Authority Required — same criteria as ferric carboxymaltose.

Managing Anaemia of Chronic Disease

ACD is managed primarily by treating the underlying inflammatory condition. Iron replacement is only indicated when concurrent true iron deficiency is confirmed (ferritin <100 µg/L with elevated CRP, or sTfR/log ferritin ratio >2). In CKD-associated ACD:

Erythropoiesis-stimulating agents (ESAs) such as epoetin alfa (Eprex®) or darbepoetin alfa (Aranesp®) are indicated for CKD stages 4–5 with Hb <100 g/L, under nephrology guidance.
IV iron is often required alongside ESAs to maintain TSAT >20% and ferritin >200 µg/L in dialysis-dependent CKD (KDIGO guidelines).
Roxadustat (Evrenzo®), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), is PBS-listed for CKD-associated anaemia in patients on dialysis (Authority Required).

Thalassaemia Trait — Management

β-thalassaemia trait and α-thalassaemia trait are benign carrier states that do not require treatment. Key management points:

Do NOT prescribe iron for thalassaemia trait — iron studies are normal, and unnecessary iron supplementation risks iatrogenic iron overload.
Patients should be informed of their carrier status and counselled regarding implications for offspring (particularly if the partner is also from an at-risk population).
Pre-conception and antenatal screening per RANZCOG guidelines — if both partners are carriers, genetic counselling and prenatal diagnosis should be offered.
FBC and iron studies should be monitored periodically (annually) to ensure that the mild anaemia remains stable and that iron overload does not develop from inappropriate supplementation.
Patients should carry a card or letter documenting their thalassaemia trait status to prevent misdiagnosis and inappropriate treatment.

Monitoring

A structured monitoring plan is essential to confirm response, detect non-adherence, and ensure iron stores are adequately replenished.

Week 1–2 Reticulocyte count — A reticulocyte response (rise in absolute reticulocyte count) confirms iron-responsive erythropoiesis. Failure to respond by week 2 suggests non-adherence, malabsorption, or incorrect diagnosis.

Week 4–6 Repeat FBC — Expect haemoglobin rise of ≥10 g/L. If no rise, reassess adherence, consider malabsorption (coeliac disease, PPI interaction), and consider haematology referral.

Month 2–3 Repeat FBC + iron studies — Haemoglobin should be normalising. Ferritin should be rising toward target. Continue oral iron.

Haemoglobin normalisation + 3 months Confirm stores replenished — Check ferritin (target >100 µg/L). If ferritin >100 µg/L and haemoglobin is normal, oral iron can be ceased. If ferritin remains <50 µg/L, continue for a further 3 months.

6–12 months post-cessation Recurrence check — Repeat FBC and iron studies 6–12 months after stopping iron to ensure no recurrence, especially if the underlying cause has not been fully resolved (e.g., ongoing HMB).

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For IV iron: Check FBC and iron studies at 4 weeks post-infusion. Haemoglobin typically rises more rapidly than with oral iron (peak response at 2–4 weeks). Ferritin may be transiently very high (reflecting recent infusion); recheck at 8–12 weeks for a true steady-state assessment.

Special Populations

🤰 Pregnancy

Prevalence: IDA affects 15–20% of pregnancies in Australia. Iron demand increases markedly from the second trimester.

Screening: FBC and iron studies at first antenatal visit (ideally <12 weeks) and repeated at 26–28 weeks per RANZCOG guidelines.

Treatment: Oral ferrous sulfate 325 mg daily is first-line. If oral iron is not tolerated or Hb <100 g/L, IV ferric carboxymaltose is safe from the second trimester onward (PBS Authority Required). IV iron polymaltose is also used but evidence for safety is less robust.

Target: Hb >110 g/L, ferritin >30 µg/L. Post-delivery, continue oral iron for 3 months to replenish stores (especially after postpartum haemorrhage).

Caution: IV iron is generally avoided in the first trimester. Ensure thalassaemia screening has been performed in at-risk populations before initiating iron therapy.

👶 Paediatrics

Prevalence: IDA is common in toddlers (12–24 months) due to high milk intake displacing iron-rich foods. Aboriginal and Torres Strait Islander children and children from refugee backgrounds are at highest risk.

Diagnostic cut-offs: Hb and MCV reference ranges are age-dependent. Ferritin <12–15 µg/L is suggestive of iron deficiency in children.

Treatment: Oral ferrous sulfate 3 mg/kg/day elemental iron for 3 months beyond haemoglobin normalisation. Liquid formulations improve compliance in young children.

Impact: Iron deficiency in infancy and early childhood is associated with long-term neurocognitive deficits, behavioural problems, and developmental delays — early detection and treatment is critical.

👴 Elderly (>65 years)

Key concern: IDA in the elderly should be assumed to be due to GI blood loss until proven otherwise. Colorectal cancer incidence rises sharply after age 50.

Common causes: NSAID/aspirin use, colonic angiodysplasia, colorectal neoplasia, atrophic gastritis (reduced acid → impaired iron absorption), CKD, chronic disease.

Polypharmacy considerations: PPIs reduce non-haem iron absorption; calcium supplements and bisphosphonates should be taken at separate times from oral iron.

Treatment: Oral iron first-line if tolerated. IV iron is preferred if malabsorption is suspected or multiple oral medications limit adherence.

🫘 Chronic Kidney Disease

Mechanism: Reduced erythropoietin production + chronic inflammation + uraemic platelet dysfunction → ACD ± IDA.

Targets (KDIGO 2012): Hb 100–115 g/L (do not exceed 130 g/L with ESA therapy). TSAT >20%, ferritin >200 µg/L in dialysis-dependent CKD.

Preferred iron: IV iron is preferred in CKD stages 4–5, especially if on haemodialysis. Ferric carboxymaltose and iron sucrose are commonly used. Oral iron has reduced absorption in CKD.

New agents: Roxadustat (Evrenzo®) — oral HIF-PHI, PBS-listed for CKD patients on dialysis. Stimulates endogenous erythropoietin and improves iron absorption.

🫁 Hepatic Impairment

Considerations: Liver disease can alter iron metabolism (hepcidin production is reduced in advanced cirrhosis). Ferritin is an acute-phase reactant and may be elevated in hepatitis and hepatocellular carcinoma independent of iron status.

Treatment: Oral iron is generally safe. IV iron should be used cautiously in active hepatitis. Avoid iron supplementation in haemochromatosis.

🛡️ Immunocompromised

Considerations: Patients on immunosuppressants (transplant recipients, biologics, chemotherapy) may have IDA from GI losses, ACD from chronic inflammation, or drug-mediated bone marrow suppression. Iron studies interpretation is complicated by concurrent inflammation.

Special note: IV iron is preferred in patients with IBD (Crohn's disease, ulcerative colitis) — oral iron may exacerbate mucosal inflammation and GI symptoms. Ferric carboxymaltose is the preferred IV formulation in IBD (ECCO guidelines).

Aboriginal and Torres Strait Islander Health

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Australians experience a significantly higher burden of iron deficiency anaemia compared with the non-Indigenous population. The AIHW reports that IDA-related hospitalisation rates are approximately 3–5 times higher in Indigenous Australians, with the greatest disparity in remote and very remote communities. This is driven by a complex interplay of nutritional, infectious, environmental, and health-system factors.

Prevalence and burden

IDA is one of the most common nutritional deficiencies in Aboriginal and Torres Strait Islander communities. Children under 5 years and women of reproductive age are disproportionately affected. Anaemia prevalence in Indigenous children in remote communities may exceed 30% in some studies.

Geographic and access barriers

Residents of remote and very remote communities often have limited access to fresh iron-rich foods, specialist services (haematology, gastroenterology), and pathology services. Serum ferritin testing and endoscopy may require medical evacuation or telehealth-facilitated referral to regional centres. Blood product availability for transfusion may be limited in remote health clinics.

Infectious aetiologies

Hookworm (Ancylostoma duodenale, Necator americanus) remains endemic in some tropical regions of northern Australia and is a significant cause of chronic GI blood loss and iron deficiency in remote Aboriginal communities. Strongyloides stercoralis, H. pylori infection, and chronic skin infections (scabies, impetigo with secondary iron loss through chronic inflammation) also contribute. Screening and treatment for soil-transmitted helminths is essential in endemic areas per RHDAustralia guidelines.

Nutritional factors

Food insecurity is a significant driver of IDA. Limited availability and high cost of fresh red meat, fruits, and vegetables in remote community stores contribute to inadequate dietary iron intake. The "Close the Gap" Healthy Stores initiative aims to improve food supply in remote communities. Culturally appropriate dietary counselling should be provided.

Thalassaemia in Indigenous Australians

α-thalassaemia trait is common in Aboriginal and Torres Strait Islander populations, particularly those from northern Australia. The single-gene deletion (-α) form is present in up to 30% of some communities. This must be considered in the differential diagnosis of microcytic anaemia to avoid inappropriate iron supplementation.

Cultural safety and communication

Health literacy and communication barriers may affect understanding of diagnosis and treatment adherence. Engaging Aboriginal Health Workers (AHWs) and Aboriginal Health Practitioners (AHPs) in the diagnosis, counselling, and follow-up process improves outcomes. Concepts of iron, blood, and transfusion may require culturally sensitive explanation. Family-centred approaches to screening and treatment are recommended.

Screening and preventive programs

The Australian Government's Indigenous health checks (MBS Item 715) include an opportunity for FBC and iron studies screening. The National Aboriginal Community Controlled Health Organisation (NACCHO) recommends routine iron status assessment at child health checks (ages 6–12 months, 12–24 months) and in all pregnant women. Iron supplementation programs (e.g., routine iron drops for infants in remote communities) should be supported.

Management adaptations

Where oral iron supply is unreliable or adherence is challenging, IV iron administered through visiting specialist services or remote health clinics may be preferred. Coordination between primary care (Aboriginal Medical Services), visiting specialist teams (Royal Flying Doctor Service), and regional hospitals is essential. Ensure that treatment of underlying infections (hookworm, H. pylori) is included in the management plan. Long-acting anthelmintics (albendazole 400 mg stat, repeated at 2 weeks) should be administered in endemic areas.

📚 References

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