From the Guidelines
Iron overload is best indicated by elevated transferrin saturation and ferritin levels, with MRI providing non-invasive quantification of iron in the liver, spleen, pancreas, heart, and brain, as recommended by the 2022 EASL clinical practice guidelines on haemochromatosis 1. The laboratory findings indicative of iron overload, also known as hemochromatosis, include:
- Elevated transferrin saturation, which is characteristic of haemochromatosis and indicates disturbed plasma iron homeostasis 1
- Elevated ferritin levels, which can indicate increased tissue iron concentrations, but are also non-specific and can be elevated in inflammatory and neoplastic conditions 1
- MRI findings, which can provide non-invasive quantification of iron in the liver, spleen, pancreas, heart, and brain, and can guide diagnosis and management 1 The initial approach to diagnosis is by indirect markers of iron stores, namely transferrin saturation (TS) or unsaturated iron-binding capacity and serum ferritin 1. Some key points to consider when interpreting these laboratory findings include:
- A cutoff TS value of 45% is often chosen for its high sensitivity for detecting C282Y homozygotes, but has a lower specificity and positive predictive value compared to higher cutoff values 1
- Serum ferritin has less biological variability than TS, but has a significant false positive rate because of elevations related to inflammation 1
- MRI techniques like T2* or FerriScan provide non-invasive iron quantification in the liver and heart, and can act as a surrogate of total body iron stores 1 It is essential to consider these laboratory findings in the context of the patient's clinical presentation, medical history, and genetic testing results to make an accurate diagnosis and develop an effective treatment plan.
From the Research
Laboratory Findings Indicative of Iron Overload (Hemochromatosis)
The following laboratory findings are indicative of iron overload (hemochromatosis) 2, 3, 4:
- Transferrin saturation levels higher than 45%
- Serum ferritin levels exceeding 200 microg/l in men and postmenopausal women
- HFE protein genotype C282Y or C282Y/H63D, which confirms the diagnosis of hereditary hemochromatosis as the cause of the iron overload
Additional Laboratory Findings
Other laboratory findings that may be useful in assessing iron overload include:
- Glycosylated ferritin levels, which may be elevated in cases of iron overload in patients undergoing regular blood transfusions 5
- Serum iron and unsaturated iron-binding capacity (UIBC) levels
- Total iron-binding capacity (TIBC) and transferrin saturation levels
- Reticulocyte hemoglobin content, percentage of hypochromic red cells, and soluble transferrin receptor, which may be useful when serum ferritin and transferrin saturation are insufficient 6
- Hepcidin levels, which may play a role in the pathophysiology of iron mobilization 6
Liver Biopsy
Liver biopsy may be useful in the diagnostic approach to iron overload disorders, by defining the amount and distribution of iron within the liver 2, 4. However, it may not be necessary in all cases, such as when serum ferritin levels are less than 1000 microg/l, transaminases are normal, and there is no hepatomegaly 2.