High transferrin saturation: what the result means and what happens next

Transferrin is the protein that carries iron around your blood, made in the liver. Lab Tests Online UK explains that transferrin attaches to iron, transports it and releases it in the bloodstream. Transferrin saturation is the percentage of transferrin that is occupied by iron, and it is calculated from measurements of iron and transferrin or TIBC.

The pattern across iron tests tells a story. According to Lab Tests Online UK, in iron deficiency iron and saturation are low and TIBC is high; in iron overload such as haemochromatosis iron and saturation are high and TIBC is low or normal; in chronic illness iron is low and TIBC low or low-normal; and in liver disease transferrin and TIBC may be low because transferrin is made in the liver.

A high transferrin saturation raises the question of iron overload. The NHS describes haemochromatosis as an inherited condition in which iron levels in the body slowly build up over many years, which if not treated can damage the liver, joints, pancreas and heart. It most often affects people of white northern European background and is particularly common where many people have a Celtic background.

NHS England's Genomics Education Programme (GeNotes) defines iron overload as transferrin saturation above 45% and serum ferritin above 200 micrograms per litre in women, and transferrin saturation above 50% and serum ferritin above 300 micrograms per litre in men, without an alternative explanation such as inflammatory conditions. Your own laboratory report will show its reference range, and a clinician interprets the combination of results in context.

Lab Tests Online UK notes that abnormal results can also arise from anaemia of infection or chronic disease, malnutrition, cirrhosis and nephrotic syndrome, and that taking the oral contraceptive pill can result in a higher TIBC result while chloramphenicol can decrease it. Some labs use only full blood count and ferritin to investigate anaemia.

GeNotes stresses that ferritin can be raised by inflammation or acute illness, which is why blood tests to confirm iron overload and exclude other causes include ferritin and fasting transferrin saturation, full blood count, liver function tests and CRP. A single abnormal value does not make a diagnosis; clinicians usually repeat or combine tests.

If both transferrin saturation and ferritin are raised and no other cause is evident, GeNotes says individuals of European origin who meet the thresholds are eligible for genomic testing, listed in the National Genomic Test Directory under R95, iron overload and hereditary haemochromatosis testing. The cause is usually variants in the HFE gene, with two common variants, C282Y and H63D. It reports that in the UK about 1 in 150 people are estimated to be homozygous for C282Y variants, the genotype at most risk, and that among such individuals 20% of men and 10% of women develop multi-organ damage, particularly liver, pancreas and bones.

Iron overload is treated by venesection, according to GeNotes, with referral to haematology and/or hepatology or gastroenterology according to local pathways. The NHS says venesection may need to be done weekly at first and then 2 to 4 times a year for life, with chelation therapy used only where regular blood removal is not easy, and that you do not need to make big dietary changes but will usually be advised to avoid iron-fortified breakfast cereals, iron or vitamin C supplements and too much alcohol.

If haemochromatosis is confirmed, genomic testing can be offered to first-degree relatives, and partners where needed to determine offspring risk, with testing of children generally from age 15 or 16.

The NHS lists symptoms of haemochromatosis that usually start between 30 and 60: feeling very tired, weight loss, weakness, joint pain, erectile dysfunction, irregular or missed periods, and brain fog, mood swings, depression and anxiety. GeNotes adds that early symptoms are non-specific and may include joint pains, lethargy, weight loss and low libido, that men are more likely than women to develop clinical features because women lose iron through menstruation, and that complications can include liver cirrhosis, diabetes, arthritis and heart failure.

The NHS advises seeing a GP if you have persistent symptoms, particularly with a northern European family background, or if a parent or sibling has haemochromatosis, even without symptoms.

On the NHS, iron studies are requested by your GP, and an abnormal pattern leads to repeat fasting samples, genetic testing where criteria are met and referral to haematology or hepatology. Private blood tests can offer iron studies directly, but a high result should be reviewed by a doctor, ideally your GP, so that confirmatory tests and any treatment are arranged.

Haemochromatosis UK is a patient-run charity that provides information and support, as the NHS notes.