What does an elevated iron saturation of 64% (above the normal range of 16-45%) on an iron, total iron-binding capacity (TIBC), and ferritin panel suggest?

From the Guidelines

An elevated iron saturation of 64% suggests possible hemochromatosis, a condition where the body absorbs too much iron, and warrants further investigation, including genetic testing for hereditary hemochromatosis (HFE gene mutations) 1. This finding is concerning because excess iron can deposit in organs like the liver, heart, and pancreas, causing damage over time. According to the EASL clinical practice guidelines on haemochromatosis, serum iron parameters, such as elevated transferrin saturation, can indicate disturbed plasma iron homeostasis, and increased alcohol consumption is an alternative cause of elevated transferrin saturation 1. Other causes of elevated iron saturation include alcoholic liver disease, hepatitis, or certain anemias. Patients should avoid iron supplements, vitamin C with meals (which enhances iron absorption), and limit alcohol consumption while undergoing evaluation. If hemochromatosis is confirmed, treatment typically involves therapeutic phlebotomy (blood removal) scheduled regularly until iron levels normalize, then maintenance phlebotomies as needed, with the frequency depending on severity but often starting at once weekly 1. Early diagnosis and treatment can prevent complications such as cirrhosis, diabetes, and heart problems. It is essential to note that the threshold levels for defining the disease remain controversial, but a serum ferritin level greater than 200 µg/mL and transferrin saturation greater than 55% suggest an increased risk for hereditary hemochromatosis and the need for further investigation 1. In patients with suspected hemochromatosis, MRI can be helpful for detection, non-invasive quantification of iron, and studying the distribution of iron in the liver, spleen, pancreas, heart, and brain 1. Overall, a comprehensive evaluation, including genetic testing and imaging studies, is necessary to confirm the diagnosis and guide management.

From the Research

Elevated Iron Saturation

• An iron saturation of 64% is above the normal range of 16-45% and may suggest iron overload disorders 2.
• Iron overload disorders can lead to increased total body iron stores and resultant end-organ damage 2, 3.
• Elevated ferritin and transferrin-iron saturation can be commonly encountered in the evaluation of elevated liver enzymes 2.

Possible Causes

• Hereditary hemochromatosis, a genetic disorder that affects iron regulation, may be a possible cause of elevated iron saturation 2, 4.
• Other possible causes of iron overload include hematologic disorders, iatrogenic causes, or chronic liver diseases 2.
• Secondary iron overload can occur due to conditions such as thalassemia syndromes, myelodysplastic syndrome, myelofibrosis, sideroblastic anemias, sickle cell disease, or pyruvate kinase deficiency 2, 5.

Diagnostic Considerations

• Confirmatory homeostatic iron regulator (HFE) genetic testing for C282Y and H63D mutations may be necessary to evaluate hereditary hemochromatosis 2.
• Magnetic resonance imaging with quantitative assessment of iron content or liver biopsy may be used to assess iron overload 2.
• Evaluation for causes of hyperferritinemia, such as chronic liver disease, malignancy, infections, kidney failure, and rheumatic conditions, should be pursued if iron overload is excluded 2.