Haemochromatosis is a common autosomal recessive condition characterised by progressive iron overload due to inappropriately increased intestinal iron absorption.
The most clinically significant form is associated with homozygosity for the C282Y mutation in the HFE gene, which affects approximately 1 in 200 people of Caucasian descent.
These individuals are at the highest risk of developing iron overload that can lead to damage in multiple organs, including:
- Liver (cirrhosis and hepatocellular carcinoma)
- Heart (cardiomyopathy and arrhythmias)
- Endocrine glands (diabetes, hypothyroidism, hypopituitarism, adrenal insufficiency)
- Joints (arthritis)
- Skin (hyperpigmentation)
- Gonads (sexual dysfunction)
Given the genetic nature of the condition, family members should be offered HFE testing. Compound heterozygotes for C282Y/H63D mutations (around 1 in 50 Caucasians) have a lower risk of iron overload but should still be considered for family screening.
H63D homozygotes and individuals with single HFE mutations may show elevated iron indices but rarely progress to clinical iron overload.
Diagnosis
Diagnosis of iron overload typically involves:
- Elevated serum ferritin:
- 200 µg/L in premenopausal women
- 300 µg/L in postmenopausal women and men
- Transferrin saturation >45%
Further assessment may include liver MRI (FerriScan) or liver biopsy. Ferritin levels >1000 µg/L are more likely to be associated with organ damage and warrant referral to a haematologist or hepatologist (gastroenterologist).
Differential Diagnosis
Elevated ferritin may also result from:
- Metabolic syndrome
- Overweight & obesity
- Diabetes mellitus
- Alcohol use (two or more standard drinks most days)
- Liver disease
- Malignancy
- Infection & inflammation
- Blood transfusions
- Excessive parenteral iron supplementation
- Iron-loading anaemias (thalassaemia, chronic haemolytic anaemia)
Treatment
Therapeutic venesection is the cornerstone of treatment and can effectively prevent organ damage when initiated early.
Australian Red Cross Lifeblood offers therapeutic venesection for eligible patients, including those with:
- C282Y homozygosity
- C282Y/H63D compound heterozygosity
- Polycythaemia vera
- Porphyria cutanea tarda
Advantages of using Lifeblood include:
- Coordination of venesection schedules and patient communication
- Blood is added to the donor pool
- Reduced clinical workload and cost
- Free for patients
The High Ferritin app
Referrals to Lifeblood are made via the High Ferritin App – a web-based tool that replaces paper and fax-based referrals.
- The doctor inputs the patient’s HFEgenotype and ferritin level.
- The app algorithm assesses eligibility for therapeutic venesection.
- A screening questionnaire determines if the patient meets general donor eligibility criteria.
- A recommended venesection schedule is generated.
- The app securely transmits patient details to Lifeblood, which contacts the patient to arrange appointments.
Other high ferritin cases
Patients with high ferritin not due to gene-positive haemochromatosis or secondary polycythaemia are not eligible for therapeutic venesection.
However, if they meet general donor criteria, they may be suitable for voluntary whole blood donation, which can be done every 12 weeks. The app allows clinicians to generate electronic referrals for these patients as well.
Development, Endorsement, and Privacy
The High Ferritin App was developed in consultation with Professor John Olynyk, a leading expert in iron disorders, and is endorsed by the Gastroenterological Society of Australia, the Haematology Society of Australia and New Zealand, and Haemochromatosis Australia.
All data transmitted through the app are handled securely in accordance with federal privacy laws. No personal or health information is stored within the app itself.
What next?
For more detailed information on haemochromatosis investigation and management, visit the Mid and North Coast HealthPathways’ Hereditary Haemochromatosis webpage (username: manchealth, password: conn3ct3d).
To get started with therapeutic venesection, visit highferritinapp.com.au to access the app or learn more.
Sources
- Goot, K., Hazeldine, S., Bentley, P., Olynyk, J., & Crawford, D. (2012). Elevated serum ferritin. What should GPs know? Australian Family Physician, 41(12), 945–949. https://www.racgp.org.au/afp/2012/december/elevated-serum-ferritin/
- High Ferritin App. Australian Red Cross Lifeblood Blood Donation Referral Tool. (2025). https://highferritin.transfusion.com.au/
