Anaemia — Med2Date

📋 Key Information Summary

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Anaemia is defined as Hb <130 g/L in men and <120 g/L in women (WHO criteria); affects approximately 5% of the Australian adult population, with higher prevalence in Aboriginal and Torres Strait Islander peoples.
Classify by mean corpuscular volume (MCV): microcytic (<80 fL), normocytic (80–100 fL), or macrocytic (>100 fL) to narrow the differential diagnosis efficiently.
Iron-deficiency anaemia (IDA) is the most common cause worldwide and in Australian general practice; always investigate for underlying cause including coeliac disease, menorrhagia, and GI blood loss — do not assume dietary deficiency alone.
Iron studies (serum ferritin, transferrin saturation, serum iron, TIBC) are the cornerstone of IDA diagnosis; ferritin <30 µg/L is highly suggestive even when within the laboratory reference range.
First-line oral iron replacement: ferrous sulfate 325 mg (105 mg elemental iron) PO daily or alternate-day dosing; alternate-day dosing improves fractional absorption and reduces GI side effects.
IV iron (ferric carboxymaltose or iron polymaltose) is indicated for intolerance to oral iron, malabsorption, chronic kidney disease, or when rapid correction is needed; available on PBS Authority Required.
Macrocytic anaemia requires distinction between megaloblastic (B12 or folate deficiency, drugs) and non-megaloblastic (alcohol, liver disease, hypothyroidism, reticulocytosis) causes.
Vitamin B12 deficiency may present with neuropsychiatric features (subacute combined degeneration of the cord, peripheral neuropathy, cognitive decline) before haematological changes are apparent.
Haemolytic anaemia is suggested by unconjugated hyperbilirubinaemia, elevated LDH, low haptoglobin, and reticulocytosis; causes include autoimmune, G6PD deficiency, hereditary spherocytosis, and microangiopathic processes.
Aplastic anaemia is a rare but life-threatening pancytopenia requiring urgent haematology referral; first-line management is immunosuppressive therapy (ATG + ciclosporin) or allogeneic stem cell transplant.
All patients with unexplained anaemia should be screened for coeliac disease (anti-tTG IgA), and those aged ≥50 with IDA require bidirectional GI endoscopy to exclude colorectal malignancy.
Aboriginal and Torres Strait Islander peoples have a 2–3-fold higher prevalence of anaemia due to higher rates of iron deficiency, chronic disease, infections, and remote-living barriers to healthcare access.
Reticulocyte count and reticulocyte production index (RPI) are essential to determine whether the bone marrow response is adequate (>2 suggests haemorrhage or haemolysis; <2 suggests hypoproliferation).

Introduction & Australian Epidemiology

Anaemia is one of the most common conditions encountered in Australian general practice, defined by the World Health Organization (WHO) as a haemoglobin (Hb) concentration below 130 g/L in males and below 120 g/L in non-pregnant females. It is not a disease in itself but rather a sign of an underlying pathological process that requires systematic investigation and classification.

In Australia, the prevalence of anaemia in the general adult population is approximately 5–6%, rising significantly in older adults (≥65 years) to 10–15%, and substantially higher in Aboriginal and Torres Strait Islander peoples (15–25% in some communities). Iron-deficiency anaemia (IDA) accounts for the majority of cases in primary care, followed by anaemia of chronic disease (ACD) and nutritional deficiencies.

The Australian Bureau of Statistics National Health Survey (2022) and the Australian Institute of Health and Welfare (AIHW) highlight that anaemia disproportionately affects populations with chronic kidney disease, chronic heart failure, malignancy, and inflammatory conditions. In children aged under 5, iron deficiency remains a significant public health concern, particularly in Indigenous communities and among recently arrived refugees.

A structured approach to the diagnosis of anaemia begins with classifying the mean corpuscular volume (MCV) into microcytic, normocytic, or macrocytic categories, followed by targeted investigations based on clinical context, age, sex, ethnicity, and associated features. This guideline provides an evidence-based framework for the classification, investigation, and management of anaemia in Australian primary care and specialist settings.

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Never treat without investigating the cause. Iron-deficiency anaemia in males and postmenopausal females is colorectal cancer until proven otherwise. The RACGP and Cancer Council Australia recommend bidirectional endoscopy (gastroscopy + colonoscopy) in all patients aged ≥50 with unexplained IDA.

Classification by MCV (Microcytic / Normocytic / Macrocytic)

The mean corpuscular volume (MCV) is the single most useful initial parameter for classifying anaemia. Measured as part of a full blood count (FBC), the MCV divides anaemias into three broad categories, each with a distinct differential diagnosis.

Category	MCV	Key Differentials	First-Line Investigations
Microcytic	<80 fL	Iron-deficiency anaemia, thalassaemia trait (α or β), anaemia of chronic disease (sometimes), sideroblastic anaemia, lead poisoning	Iron studies, Hb electrophoresis, blood film, lead level if suspected
Normocytic	80–100 fL	Anaemia of chronic disease/inflammation, chronic kidney disease, acute blood loss, haemolysis, mixed deficiency, bone marrow failure, hypothyroidism	CRP/ESR, eGFR, reticulocyte count, LDH, haptoglobin, blood film, haemolysis screen
Macrocytic	>100 fL	B12 deficiency, folate deficiency, alcohol excess, liver disease, hypothyroidism, drugs (methotrexate, hydroxycarbamide, azathioprine, phenytoin), myelodysplastic syndrome, reticulocytosis	B12, folate (RBC folate preferred), reticulocyte count, TFTs, LFTs, blood film, consider MDS workup

The Reticulocyte Production Index (RPI)

The reticulocyte count corrected for the degree of anaemia — the Reticulocyte Production Index (RPI) — is essential for distinguishing between inadequate marrow response (hypoproliferative) and appropriate or excessive response (blood loss or haemolysis).

RPI	Interpretation	Indicates
<2	Inadequate marrow response	Hypoproliferative: iron deficiency, B12/folate deficiency, ACD, CKD, marrow infiltration, aplastic anaemia
≥2	Adequate/excessive marrow response	Haemorrhage (acute or chronic blood loss) or haemolysis

RPI formula: RPI = (Reticulocyte % × Patient Hb / Normal Hb) × (1 / Maturation factor). The maturation factor is 1.0 for Hb ≥100 g/L, 1.5 for Hb 80–99, 2.0 for Hb 60–79, and 2.5 for Hb <60.

Iron-Deficiency Anaemia (Features, Iron Studies, Management)

Clinical Features

Iron-deficiency anaemia (IDA) develops in stages: iron depletion (reduced stores, normal Hb), iron-deficient erythropoiesis (stores exhausted, Hb still normal), and finally frank IDA. Symptoms reflect tissue hypoxia and include fatigue, exertional dyspnoea, palpitations, pallor, angular stomatitis, glossitis, koilonychia (spoon nails), pica (pagophagia — ice craving), restless legs syndrome, and in children, developmental delay and behavioural changes.

Iron Studies Interpretation

Parameter	Iron Deficiency	Anaemia of Chronic Disease	Thalassaemia Trait	Normal
Serum ferritin	↓↓ (<30 µg/L)	Normal or ↑	Normal or ↑	30–300 µg/L
Serum iron	↓	↓	Normal or ↑	10–30 µmol/L
TIBC	↑	↓ or normal	Normal	45–72 µmol/L
Transferrin saturation	↓ (<16%)	↓	Normal or ↑	20–50%
Soluble transferrin receptor (sTfR)	↑	Normal	Normal	Age/sex-dependent
MCV	↓ (late)	Normal or ↓	↓↓	80–100 fL
RDW	↑	Normal	Normal	11.5–14.5%

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Ferritin is an acute-phase reactant. A normal or elevated ferritin does not exclude iron deficiency in the setting of infection, inflammation, malignancy, or liver disease. In such cases, use transferrin saturation (<16%) and soluble transferrin receptor (sTfR) to differentiate IDA from ACD. A sTfR/log ferritin ratio >2 supports true iron deficiency.

Investigating the Cause

IDA is a sign, not a diagnosis. Common causes in Australian practice include:

Women of reproductive age: Menorrhagia (most common), pregnancy, menorrhagia-related losses >80 mL/cycle
Males and postmenopausal females: GI blood loss — colorectal cancer, peptic ulcer disease, angiodysplasia, coeliac disease, inflammatory bowel disease, NSAID gastropathy, haemorrhoids
Children: Cow's milk excess (low bioavailability, GI microbleeds), coeliac disease, poor dietary diversity, hookworm in tropical NT/QLD
Other: Malabsorption (coeliac disease, bariatric surgery, PPI use), chronic blood donation, haematuria (rare), hereditary haemorrhagic telangiectasia

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Red flags for malignancy: Unintentional weight loss, change in bowel habit, PR bleeding, abdominal mass, new iron deficiency in a male >50 or female >60. Refer urgently for colonoscopy ± gastroscopy per RACGP/Cancer Council Australia guidelines.

Management of Iron-Deficiency Anaemia

Oral Iron Replacement

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Ferrous Sulfate

Ferro-Gradumet® · Generic · Oral iron salt

Adult dose 325 mg (105 mg elemental iron) PO once daily or on alternate days; take on empty stomach with vitamin C 200 mg to enhance absorption

Paediatric dose 3–6 mg/kg/day elemental iron PO in 1–2 divided doses

Duration 3–6 months after Hb normalisation to replenish stores (target ferritin >100 µg/L)

Renal adjustment None required

Side effects Constipation, nausea, epigastric discomfort, dark stools; alternate-day dosing reduces GI side effects by ~30%

PBS status ✔ PBS General Benefit

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Ferrous Fumarate

Ferro-Tab® · Generic · Oral iron salt

Adult dose 322 mg (105 mg elemental iron) PO once daily or alternate days

Paediatric dose As per ferrous sulfate: 3–6 mg/kg/day elemental iron

PBS status ✔ PBS General Benefit

Intravenous Iron

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Ferric Carboxymaltose

Ferinject® · IV iron

Adult dose Up to 1000 mg IV infusion over ≥15 min; may repeat if total deficit >1000 mg (calculate using Ganzoni formula)

Indications Oral intolerance, malabsorption (coeliac, IBD, bariatric), CKD (eGFR <30), chronic heart failure, ongoing losses exceeding oral absorption capacity

Key risk Hypophosphataemia (transient, usually self-limiting); risk of serious hypophosphataemia with repeated dosing — check phosphate post-infusion

PBS status ⚠ PBS Authority Required

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Iron Polymaltose (Iron(III) Hydroxide Polymaltose)

Ferro® · IV iron

Adult dose Total dose infusion (TDI) calculated by Ganzoni formula: Weight (kg) × (Target Hb − Actual Hb) (g/L) × 0.24 + 500 mg (stores). Infuse over 4–6 hours.

Note Slower infusion rate required; higher anaphylaxis risk compared to ferric carboxymaltose. Largely superseded by ferric carboxymaltose in Australian practice.

PBS status ⚠ PBS Authority Required

Ganzoni Formula for Total Iron Deficit

Total iron deficit (mg) = Body weight (kg) × (Target Hb − Actual Hb) (g/L) × 0.24 + Iron stores (mg). Use 500 mg for stores if body weight >35 kg, or 15 mg/kg if <35 kg. Target Hb is typically 150 g/L.

Monitoring Response to Treatment

Reticulocyte count at 7–10 days — expect a reticulocyte peak (corrected count >2%) indicating adequate marrow response
Repeat FBC at 4 weeks — expect Hb rise of 10–20 g/L per month
Repeat iron studies at 8–12 weeks — target ferritin >100 µg/L
If no response at 4 weeks: reassess compliance, consider malabsorption, coeliac screening, check for ongoing blood loss

Haemolytic & Aplastic Anaemia

Haemolytic Anaemia

Haemolytic anaemia results from premature red blood cell destruction, either intravascular (within the circulation) or extravascular (within the reticuloendothelial system — spleen, liver, bone marrow). The hallmark finding is an elevated reticulocyte count (RPI >2) with characteristic laboratory features.

Diagnostic Hallmarks of Haemolysis

Parameter	Finding in Haemolysis	Mechanism
Reticulocyte count	↑↑ (>100 × 10⁹/L)	Compensatory marrow response
Unconjugated bilirubin	↑	Released from haem catabolism
LDH	↑↑	Released from lysed RBCs
Haptoglobin	↓↓ (may be undetectable)	Binds free haemoglobin and is cleared
Blood film	Spherocytes, schistocytes, target cells, bite cells, agglutination	Depends on underlying cause

Classification and Causes

Category	Examples	Key Investigations
Immune — Autoimmune haemolytic anaemia (AIHA)	Warm AIHA (IgG, SLE, CLL, lymphoma), Cold agglutinin disease (IgM, Mycoplasma, EBV)	Direct antiglobulin test (DAT / Coombs); warm: spherocytes; cold: agglutination on film
Immune — Alloimmune	Haemolytic disease of the newborn (HDN), transfusion reactions	Blood group and antibody screen, DAT on neonatal blood
Hereditary — Membrane defects	Hereditary spherocytosis, hereditary elliptocytosis	Blood film (spherocytes), eosin-5-maleimide (EMA) flow cytometry test, osmotic fragility
Hereditary — Enzyme defects	G6PD deficiency (X-linked, significant in Mediterranean, African, South-East Asian populations in Australia), pyruvate kinase deficiency	G6PD assay (NOT during acute haemolytic crisis — false negatives occur); blood film: bite cells, Heinz bodies
Hereditary — Haemoglobinopathies	Sickle cell disease, HbE disease, unstable haemoglobins	Hb electrophoresis, HPLC, genetic testing
Microangiopathic (MAHA)	TTP, HUS, DIC, HELLP syndrome, mechanical heart valves, malignant hypertension	Blood film (schistocytes), LDH, platelet count, coagulation screen, ADAMTS13 activity (TTP), stool culture + Shiga toxin (HUS)
Infections	Malaria (relevant to returned travellers and PNG border regions), babesiosis, Clostridium perfringens septicaemia	Thick and thin blood films (malaria parasite screen), rapid malaria antigen test

Management of Autoimmune Haemolytic Anaemia (AIHA)

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Prednisolone

Panafcortelone® · Generic · Corticosteroid

Adult dose 1–1.5 mg/kg/day PO (typically 75–100 mg) for warm AIHA; taper over 6–12 months once Hb stabilises >100 g/L

Response Expect Hb rise within 1–2 weeks; 80% respond to corticosteroids

Steroid-sparing Rituximab (MabThera®) 375 mg/m² IV weekly × 4 doses — indicated for steroid-dependent or refractory AIHA. Azathioprine or mycophenolate as steroid-sparing agents.

PBS status ✔ PBS General Benefit (prednisolone)

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G6PD Deficiency — Avoid these triggers: Primaquine, dapsone, sulfonamides, nitrofurantoin, rasburicase, naphthalene (mothballs), fava beans. Acute haemolysis may require transfusion support and emergency care. The condition is particularly relevant in Australian communities with Mediterranean, Middle Eastern, African, and South-East Asian heritage.

Aplastic Anaemia

Aplastic anaemia is a rare, life-threatening condition characterised by pancytopenia (anaemia, neutropenia, thrombocytopenia) with a hypocellular bone marrow (<25% cellularity on trephine biopsy). It may be acquired (most common: autoimmune, idiopathic, post-hepatitis, drug-related) or inherited (Fanconi anaemia, dyskeratosis congenita).

Severity Classification (Camitta Criteria)

Moderate

Non-Severe Aplastic Anaemia

Pancytopenia not meeting severe criteria; bone marrow cellularity 20–30%; may be stable for months-years

Setting: Haematology outpatient monitoring

Severe

Severe Aplastic Anaemia (SAA)

Bone marrow cellularity <25% plus at least 2 of: neutrophils <0.5 × 10⁹/L, platelets <20 × 10⁹/L, reticulocytes <20 × 10⁹/L

Setting: Tertiary haematology — urgent referral

Management of Aplastic Anaemia

Allogeneic haemopoietic stem cell transplant (HSCT): First-line for patients aged <40 with a matched sibling donor; cure rate 70–90%
Immunosuppressive therapy (IST): Anti-thymocyte globulin (ATG, equine) + ciclosporin — first-line for patients >40 or without a matched donor; response rate 60–70%
Eltrombopag (Revolade®): Thrombopoietin receptor agonist; PBS-listed for refractory SAA; increasingly used in combination with IST as frontline per NIH protocols
Supportive care: Transfusion support (irradiated, CMV-safe blood products), antimicrobial prophylaxis, G-CSF for severe neutropenia

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Aplastic anaemia is a haematological emergency. All patients require urgent referral to a haematology centre with transplant capability. Do not delay referral while awaiting investigations. Median survival without treatment is 6–12 months for severe disease.

Macrocytic Anaemia (B12, Folate, Drugs, Thalassaemia)

Macrocytic anaemia (MCV >100 fL) is broadly divided into megaloblastic (impaired DNA synthesis) and non-megaloblastic categories. Accurate classification is essential as the aetiologies and treatments differ significantly.

Megaloblastic vs Non-Megaloblastic

Feature	Megaloblastic	Non-Megaloblastic
Mechanism	Impaired DNA synthesis (nuclear-cytoplasmic asynchrony)	Altered RBC membrane lipids or increased membrane surface area
Causes	B12 deficiency, folate deficiency, drugs (methotrexate, hydroxycarbamide, azathioprine, trimethoprim, phenytoin, zidovudine), myelodysplastic syndrome, orotic aciduria	Alcohol excess, liver disease, hypothyroidism, reticulocytosis, spurious (cold agglutinins, hyperglycaemia)
Blood film	Macro-ovalocytes, hypersegmented neutrophils (>5 lobes), Howell-Jolly bodies	Round macrocytes, target cells (liver), polychromasia (reticulocytes)
Reticulocyte count	↓ (hypoproliferative)	Variable — ↑ in haemolysis/bleeding

Vitamin B12 Deficiency

Vitamin B12 (cobalamin) is absorbed in the terminal ileum via intrinsic factor produced by gastric parietal cells. Body stores are substantial (2–5 mg), meaning deficiency typically develops over years. Causes include pernicious anaemia (autoimmune gastritis — most common in Australia), dietary deficiency (vegan/strict vegetarian diets), gastrectomy/bariatric surgery, terminal ileum disease (Crohn's, coeliac, surgical resection), and medications (metformin, long-term PPI, nitrous oxide).

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Neuropsychiatric manifestations of B12 deficiency may be irreversible. Subacute combined degeneration of the spinal cord (posterior and lateral column demyelination), peripheral neuropathy, cognitive impairment, depression, and psychosis can occur with or without anaemia. Always check B12 in patients with unexplained neurological symptoms, even if Hb and MCV are normal.

B12 Replacement

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Hydroxocobalamin

Cytamen® · IM injection · Preferred for B12 replacement

Adult dose — loading 1000 µg IM alternate days for 2 weeks (7 doses total) for neurological involvement or severe deficiency

Adult dose — maintenance 1000 µg IM every 2–3 months (lifelong if pernicious anaemia)

Note Hydroxocobalamin preferred over cyanocobalamin due to longer half-life and tissue retention. Monitor potassium during initial treatment (risk of hypokalaemia from rapid erythropoiesis).

PBS status ✔ PBS General Benefit

Folate Deficiency

Folate (vitamin B9) is absorbed in the proximal jejunum. Body stores are limited (5–20 mg), so deficiency develops within months. Causes include poor dietary intake (elderly, alcohol dependence, institutionalised patients), malabsorption (coeliac disease, tropical sprue), increased demand (pregnancy, haemolysis, malignancy, exfoliative dermatitis), and drugs (methotrexate, trimethoprim, phenytoin, sulfasalazine).

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Never give folate alone without excluding B12 deficiency. Folate supplementation can mask the haematological signs of B12 deficiency while neurological damage (subacute combined degeneration) progresses irreversibly. Always check B12 levels before initiating folate therapy.

Folate Replacement

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Folic Acid

Generic · Oral vitamin

Adult dose — treatment 5 mg PO daily for 4 months (until Hb normalises and stores replenished)

Adult dose — prophylaxis 0.5 mg PO daily — pregnancy (ideally start 1 month pre-conception), chronic haemolytic anaemia, methotrexate users

PBS status ✔ PBS General Benefit

Drug-Induced Macrocytosis

Many commonly prescribed medications cause macrocytosis, often without frank anaemia. The most frequent offenders in Australian practice include:

Methotrexate: Interferes with folate metabolism — macrocytosis expected and dose-dependent; check folate levels
Hydroxycarbamide (Hydrea®): Used in myeloproliferative disorders; macrocytosis is a known effect
Azathioprine / 6-mercaptopurine: Commonly used in IBD and transplant; megaloblastic changes on blood film
Trimethoprim: Dihydrofolate reductase inhibitor; risk of megaloblastic change with prolonged use
Phenytoin / Carbamazepine / Phenobarbitone: Anticonvulsants that impair folate absorption and metabolism
Metformin: Reduces B12 absorption via ileal calcium-dependent membrane action — up to 10–30% of long-term users develop B12 deficiency
Proton pump inhibitors (PPIs) and H2-receptor antagonists: Reduce gastric acid and hence B12 absorption with chronic use
Zidovudine (AZT): Known cause of macrocytic anaemia in HIV-positive patients

Thalassaemia — A Special Consideration in Microcytic Anaemia

While traditionally discussed under microcytic anaemias, thalassaemia deserves emphasis in the Australian context due to our multicultural population. β-thalassaemia trait (minor/intermedia) and α-thalassaemia trait are common in Australians of Mediterranean, Middle Eastern, South-East Asian, Indian subcontinent, and African descent. The trait is characterised by mild microcytic anaemia (Hb 100–130 g/L), low MCV (60–75 fL), and disproportionately high RBC count (normal or elevated), with normal or elevated ferritin and transferrin saturation.

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Distinguishing thalassaemia trait from IDA: In thalassaemia trait, the RDW is typically normal (homogeneous microcytosis), RBC count is normal or elevated, ferritin is normal or raised, and the MCV is disproportionately low for the degree of anaemia. In IDA, the RDW is elevated (anisocytosis), RBC count tends to be low, and ferritin is low. If uncertain, perform Hb electrophoresis/HPLC (for β-thal) or genetic testing (for α-thal).

Thalassaemia in Australia

Type	Clinical Severity	Management
β-thalassaemia minor (trait)	Asymptomatic or mild microcytic anaemia; no treatment required	Genetic counselling for at-risk couples; avoid unnecessary iron supplementation
β-thalassaemia intermedia	Moderate anaemia; variable transfusion requirements; iron overload may develop	Haematology follow-up; intermittent transfusion; iron chelation if ferritin >1000 µg/L; consider hydroxycarbamide, luspatercept
β-thalassaemia major	Severe transfusion-dependent anaemia from infancy; hepatosplenomegaly; bony deformities; iron overload cardiomyopathy	Lifelong regular transfusion (every 3–4 weeks); iron chelation (deferasirox, deferoxamine); HSCT for cure in eligible patients; specialist haematology management at major centres
HbH disease (α-thalassaemia)	Moderate haemolytic anaemia; may require occasional transfusion	Haematology monitoring; avoid oxidant drugs; splenectomy in select cases
Hydrops fetalis (Hb Bart's — α-thalassaemia major)	Usually fatal in utero; requires intrauterine transfusion	Antenatal screening and genetic counselling in at-risk populations

Investigations

The following investigations should be performed systematically based on MCV classification and clinical context. All tests are widely available through Australian pathology services (e.g., Sonic Healthcare, Clinical Labs, Healius) with Medicare-funded MBS items.

Essential Full Blood Count (FBC) with differential MCV, MCH, MCHC, RDW, RBC count, WCC, platelets, haemoglobin. MBS Item 65070. Available in all settings including point-of-care (e.g., iSTAT in remote clinics).

Essential Blood Film (Peripheral Smear) Morphological assessment: microcytes, macro-ovalocytes, spherocytes, schistocytes, target cells, hypersegmented neutrophils, rouleaux formation. MBS Item 65100.

Essential Iron Studies Serum ferritin, serum iron, TIBC, transferrin saturation (TSAT). MBS Item 66078. Essential for all microcytic and unexplained normocytic anaemias.

Essential Reticulocyte Count Assess marrow response; calculate RPI. MBS Item 65085.

Available Vitamin B12 and Folate (RBC folate preferred) MBS Item 66512 (B12), 66515 (folate). Check for all macrocytic anaemias. Serum folate reflects recent intake; RBC folate reflects tissue stores.

Available Haemolysis Screen LDH (MBS Item 66575), unconjugated bilirubin, haptoglobin (MBS Item 66506), direct antiglobulin test (DAT/Coombs) (MBS Item 69304). Order when RPI >2 or clinical features of haemolysis.

Available Haemoglobin Electrophoresis / HPLC MBS Item 65135. For suspected thalassaemia trait, haemoglobinopathies. β-thal trait shows elevated HbA2 (>3.5%). α-thal trait may require genetic testing.

Available G6PD Assay MBS Item 66585. Do NOT perform during an acute haemolytic episode (young RBCs have higher G6PD activity, giving false negatives). Test 6–8 weeks post-recovery.

Available Coeliac Serology (Anti-tTG IgA) MBS Item 66638. Screen all patients with unexplained IDA. Must be on a gluten-containing diet for accurate results. Check total IgA — IgA deficiency may cause false negatives.

Available Renal Function (eGFR) Anaemia of CKD: normocytic, hypoproliferative. eGFR <30 mL/min/1.73m² is the usual threshold for CKD-related anaemia.

Available Thyroid Function Tests (TFTs) MBS Item 66719. Hypothyroidism is a reversible cause of normocytic or macrocytic anaemia.

Available Inflammatory Markers (CRP, ESR) MBS Item 66330 (CRP), 65080 (ESR). Elevated CRP/ESR with normal/elevated ferritin and low TSAT suggests anaemia of chronic disease.

Referral Bone Marrow Aspiration and Trephine Biopsy Indicated for suspected aplastic anaemia, myelodysplastic syndrome, leukaemia, myelofibrosis, or unexplained pancytopenia. Requires haematology referral.

Referral Upper and Lower GI Endoscopy Bidirectional endoscopy for all patients ≥50 years with unexplained IDA, or any age with red-flag symptoms. Also for coeliac disease diagnosis (duodenal biopsy). MBS Items 30473, 32222.

Empirical Therapy & Directed Management

Anaemia of Chronic Disease (ACD) / Anaemia of Inflammation

ACD is the second most common anaemia in Australian practice after IDA, driven by inflammatory cytokines (IL-6, TNF-α, IFN-γ) that increase hepcidin production, reducing iron absorption and trapping iron in macrophages. ACD is seen in chronic infections, autoimmune conditions (RA, SLE, IBD), malignancy, and CKD.

Key Features of ACD

Normocytic or mildly microcytic anaemia; typically mild-moderate (Hb 90–110 g/L)
Iron studies: low serum iron, low TSAT, normal or elevated ferritin, normal or low TIBC
Elevated hepcidin (functional iron deficiency despite adequate stores)
Differentiate from IDA using sTfR/log ferritin ratio (<1 in ACD, >2 in IDA)

Management of ACD

Treat the underlying condition: Optimal management of the inflammatory disease (e.g., DMARDs for RA, anti-TNF for IBD) will often improve the anaemia
IV iron supplementation: Indicated in CKD, heart failure, and when functional iron deficiency co-exists (ferric carboxymaltose preferred for rapid correction)
Erythropoiesis-stimulating agents (ESAs): Epoetin alfa (Eprex®) and darbepoetin alfa (Aranesp®) — indicated in CKD-related anaemia (eGFR <30) and chemotherapy-induced anaemia; PBS Authority Required; target Hb 100–120 g/L
Blood transfusion: Reserved for symptomatic anaemia (Hb <70 g/L) or haemodynamic instability; single-unit transfusion with reassessment preferred

Quick Reference: Approach by MCV Category

Microcytic (MCV <80)

Order iron studies first. If ferritin ↓, treat as IDA. If ferritin normal/↑, consider Hb electrophoresis (thalassaemia) or sTfR (ACD).

N/A

Always investigate the cause of IDA — never assume dietary deficiency.

Normocytic (MCV 80–100)

Check RPI. If RPI <2: CRP, eGFR, iron studies (ACD/CKD). If RPI ≥2: haemolysis screen (LDH, haptoglobin, bilirubin, DAT) or assess for acute blood loss.

N/A

Mixed deficiency (iron + B12) may present as normocytic — check both if uncertain.

Macrocytic (MCV >100)

Check B12, folate, LFTs, TFTs, alcohol history, medication review. Blood film for megaloblastic vs non-megaloblastic features.

N/A

Rule out B12 deficiency before giving folate. Check MDS workup if B12/folate normal.

Blood Transfusion

Red cell transfusion is indicated for symptomatic anaemia causing haemodynamic compromise or end-organ ischaemia, typically when Hb <70 g/L (restrictive threshold per Australian Patient Blood Management guidelines, ACSQHC). A restrictive strategy (target Hb 70–80 g/L) is preferred in most clinical settings to minimise transfusion-related risks.

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Patient Blood Management (PBM): The ACSQHC National Blood Authority recommends a three-pillar PBM approach: (1) Optimise red cell mass pre-procedurally (iron, B12, folate, EPO), (2) Minimise perioperative blood loss (tranexamic acid, cell salvage, restrictive transfusion triggers), (3) Optimise physiological tolerance of anaemia (fluid management, oxygen delivery). All Australian hospitals should have PBM programs in place.

Monitoring

Week 1–2

Reticulocyte response: After initiating iron or B12 replacement, expect a reticulocyte peak at 7–10 days. This confirms marrow responsiveness and is the earliest marker of treatment efficacy.

Week 4

Repeat FBC: Expect Hb rise of 10–20 g/L per month with appropriate iron replacement. If no rise: check compliance, assess for malabsorption (coeliac disease), and investigate for ongoing blood loss.

Week 8–12

Repeat iron studies: Target ferritin >100 µg/L (not just Hb normalisation). Continuing treatment for 3–6 months after Hb correction is essential to replenish iron stores.

Month 3–6

Completion of therapy: For IDA, discontinue oral iron once ferritin >100 µg/L and Hb has been normal for ≥3 months. For B12 deficiency (pernicious anaemia), lifelong IM hydroxocobalamin every 2–3 months is required. For folate deficiency, treat for 4 months and address the underlying cause.

Ongoing

Long-term surveillance: Patients with recurrent IDA need investigation for chronic blood loss (GI referral). Patients with pernicious anaemia should have annual B12 levels and thyroid function (associated autoimmune thyroiditis). Thalassaemia major patients require lifelong iron overload monitoring (serum ferritin, cardiac and hepatic MRI T2*).

Special Populations

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Pregnancy

Prevalence: Iron deficiency affects 20–40% of Australian pregnant women. Physiological haemodilution lowers Hb but true anaemia (Hb <110 g/L in T1/T3, <105 g/L in T2) requires treatment.

Oral iron: Ferrous sulfate 325 mg daily or alternate days is safe in pregnancy. Constipation is common — use osmotic laxatives (macrogol) if needed.

IV iron: Ferric carboxymaltose is safe from T2 onwards. Iron polymaltose is also acceptable. Avoid IV iron in T1 unless severe and refractory. Requires PBS Authority approval.

Folate: All women planning pregnancy should take 0.5 mg folic acid daily, starting at least 1 month before conception and continuing through T1. Higher dose (5 mg) for those on anticonvulsants, with prior NTD-affected pregnancy, BMI >30, or pre-existing diabetes.

B12: Deficiency is uncommon but may occur in strict vegans or those with pernicious anaemia. Safe to replace with hydroxocobalamin IM.

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Paediatrics

Prevalence: Iron deficiency affects 8–15% of Australian toddlers (1–3 years), higher in Indigenous communities and those consuming excessive cow's milk (>500 mL/day).

Oral iron dose: 3–6 mg/kg/day elemental iron PO in 1–2 divided doses. Ferrous sulfate liquid (30 mg elemental iron/mL) is preferred for young children. Treat for 3 months after Hb normalisation.

B12 deficiency: Consider in infants of B12-deficient mothers (vegan diets), exclusively breastfed without supplementation, or those with undiagnosed pernicious anaemia in the mother. Presents with failure to thrive, developmental regression, and megaloblastic anaemia.

Thalassaemia screening: Newborn screening programs in some states include Hb electrophoresis. Infants with Hb Bart's on newborn screen require follow-up for α-thalassaemia.

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Elderly (≥65 years)

Prevalence: 10–15% of community-dwelling Australians aged ≥65 are anaemic; up to 50% in residential aged care. Multifactorial causes are common (ACD + IDA + B12 + CKD + myelodysplasia).

Key considerations: Polypharmacy-related causes (metformin → B12, PPI → B12, methotrexate → folate, NSAIDs → GI blood loss). Always perform a thorough medication review. Pernicious anaemia is more common in this age group.

Transfusion: Use restrictive thresholds (Hb <70 g/L) unless symptomatic or haemodynamically compromised. Consider frailty, comorbidities, and patient goals of care.

MDS risk: Myelodysplastic syndrome incidence increases with age (median age at diagnosis 70+). Consider MDS workup in unexplained macrocytic or refractory anaemia with dysplastic blood film features.

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Chronic Kidney Disease

Pathophysiology: Reduced erythropoietin (EPO) production, functional iron deficiency (hepcidin-mediated), uraemic bone marrow suppression, and shortened RBC lifespan.

Thresholds: Investigate anaemia in CKD when eGFR <45 mL/min/1.73m². Consider ESA therapy when eGFR <30, Hb <100 g/L, and after iron stores optimised (ferritin >100, TSAT >20%).

Iron in CKD: IV iron (ferric carboxymaltose) preferred due to hepcidin-mediated oral malabsorption. PBS Authority Required for IV iron in CKD.

ESA therapy: Epoetin alfa (Eprex®) or darbepoetin alfa (Aranesp®). Target Hb 100–115 g/L. Avoid ESA use targeting Hb >130 g/L (increased cardiovascular risk per TREAT trial). PBS Authority Required.

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Hepatic Impairment

Anaemia pattern: Non-megaloblastic macrocytosis is common in chronic liver disease (altered RBC membrane lipids). May also have concurrent IDA from variceal/portal hypertensive gastropathy bleeding.

Drug metabolism: Standard iron doses do not require hepatic adjustment. Methotrexate and azathioprine require caution — macrocytosis may be drug-related.

Transfusion: Patients with liver disease may have impaired haemostasis; balance transfusion need against volume overload risk in portal hypertension/ascites.

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Immunocompromised

HIV: Multifactorial anaemia (ACD, drug-related — zidovudine, opportunistic infections, malignancy). Macrocytosis from zidovudine is common.

Post-transplant: Azathioprine and mycophenolate cause macrocytic/megaloblastic changes. Anaemia may indicate graft rejection, infection, or PTLD.

Chemotherapy: Myelosuppression is expected. ESA use for chemotherapy-induced anaemia if Hb <100 g/L, per eviQ/ESMO guidelines. PBS Authority Required.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Aboriginal and Torres Strait Islander peoples experience significantly higher rates of anaemia compared to the non-Indigenous Australian population. The AIHW reports that anaemia prevalence in Indigenous Australians is 2–3 times higher across all age groups, with particularly elevated rates in remote and very remote communities. The Australian Aboriginal and Torres Strait Islander Health Survey (2018–19) found iron-deficiency anaemia in up to 25% of Indigenous children aged under 5 in some regions.

Key Determinants of Higher Anaemia Prevalence

Iron deficiency

Dietary factors including limited access to fresh, iron-rich foods in remote communities (food insecurity); high consumption of tea (inhibits iron absorption); reliance on processed, low-nutrient foods from community stores. The Remote Stores Project and Good Food Systems initiatives aim to improve food security.

Chronic infections

Higher rates of chronic skin infections (scabies, impetigo), rheumatic heart disease, chronic suppurative lung disease (bronchiectasis), helminth infections (hookworm in tropical QLD/NT), and chronic hepatitis B contribute to anaemia of chronic disease.

Chronic kidney disease

CKD prevalence is 2–3 times higher in Indigenous Australians, contributing to EPO-deficient anaemia. The eGFR correction factor for Indigenous patients (where previously used) has been removed per recent Kidney Health Australia recommendations, but vigilance for CKD-related anaemia remains essential.

Rheumatic fever & RHD

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are almost exclusively diseases of Indigenous Australians. Chronic inflammation from RHD contributes to ACD. RHD registers exist in NT, QLD, SA, and WA.

Thalassaemia

α-thalassaemia trait is common in some Indigenous communities (up to 30% prevalence in some regions of northern Australia), which may confound the interpretation of microcytic anaemia and lead to misdiagnosis as IDA.

Access to healthcare

Remote-living Indigenous Australians face barriers including limited pathology services, transport difficulties for specialist appointments, reduced pharmacy access (particularly for IV iron infusions requiring day-stay), and culturally unsafe healthcare environments. Aboriginal Community Controlled Health Organisations (ACCHOs) are the preferred model of care.

Cultural considerations

Gender-specific health checks may require same-sex health practitioners. Health literacy varies significantly. Kinship obligations and Sorry Business may affect appointment adherence. The concept of "anaemia" may not translate directly in all Aboriginal languages — use culturally appropriate communication with interpreter support (e.g., Aboriginal Health Workers/Practitioners).

Child and maternal health

Iron deficiency in Indigenous children is associated with developmental delay and poor educational outcomes. Antenatal anaemia prevalence is 2–4 times higher. The National Aboriginal and Torres Strait Islander Maternal and Child Health Strategy prioritises early iron screening and supplementation in pregnancy and infancy.

Recommended Actions for Clinicians

Screen proactively: FBC and iron studies should be part of routine health assessments for Indigenous Australians (MBS Item 715 health check), particularly children under 5, pregnant women, and those with chronic disease.
Investigate for concurrent causes: In remote communities, consider hookworm (stool microscopy), chronic infections (CRP, ESR), RHD (ECO), and CKD (eGFR, urinalysis) as co-contributors.
Engage Aboriginal Health Workers: AHWs and Aboriginal Health Practitioners (AHPs) are essential for building trust, facilitating adherence, and providing culturally safe care. They should be involved in counselling about iron supplementation, dietary modification, and follow-up.
Point-of-care testing: Utilise portable Hb/Hct analysers (e.g., HemoCue) available in many ACCHOs and remote clinics for immediate assessment when laboratory services are distant.
Consider food security: When addressing iron deficiency, acknowledge and address the social determinants of health — food access, housing, and income — rather than solely prescribing oral iron. Refer to community nutrition programs where available.
Follow-up and recall systems: Implement robust recall and reminder systems (e.g., Communicare, MMEx clinical software) to ensure treatment completion and re-check of iron studies after replacement therapy.

📚 References

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2. Australian Institute of Health and Welfare. Aboriginal and Torres Strait Islander Health Performance Framework: Anaemia. Canberra: AIHW; 2023.
3. Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice (Red Book) — Iron deficiency investigation. 9th ed. Melbourne: RACGP; 2018 (updated 2023).
4. Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L. Iron deficiency anaemia. Lancet. 2016;387(10021):907–916.
5. National Blood Authority (Australia). Patient Blood Management Guidelines: Module 2 — Perioperative. Canberra: NBA; 2012 (updated 2023).
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7. Stoffel NU, Cercamondi CI, Brittenham G, et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol. 2017;4(11):e524–e533.
8. Kidney Health Australia. Chronic Kidney Disease Management in Primary Care. 4th ed. Melbourne: Kidney Health Australia; 2020.
9. Camitta BM, Thomas ED, Nathan DG, et al. Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality. Blood. 1976;48(1):63–70.
10. Killick SB, Bown N, Cavenagh J, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016;172(2):187–207.
11. Green R, Datta Mitra A. Megaloblastic anemias: nutritional and other causes. Med Clin North Am. 2017;101(2):297–317.
12. Cancer Council Australia / RACGP. Early detection of cancers: Clinical practice guidelines — Colorectal cancer screening and investigation of iron deficiency. Sydney: Cancer Council Australia; 2023.
13. DeLoughery TG. Microcytic anemia. N Engl J Med. 2014;371(14):1324–1331.
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15. NHMRC. National Statement on Ethical Conduct in Aboriginal and Torres Strait Islander Health Research. Canberra: NHMRC; 2018.
16. Australian Bureau of Statistics. National Health Survey: First Results, 2022. Canberra: ABS; 2023.