From the Guidelines
Elevated iron and saturation with low ferritin and transferrin suggests a condition called iron overload with paradoxical iron deficiency, and the most appropriate management approach is to first identify and treat the underlying cause, with phlebotomy being a potential treatment option to reduce iron stores, as recommended by the most recent guidelines 1. The condition typically occurs in specific situations such as liver disease (particularly alcoholic liver disease or hepatitis), protein malnutrition, or anemia of chronic disease with concurrent iron therapy.
- Complete cessation of alcohol consumption is essential if alcoholic liver disease is suspected.
- Nutritional support with a protein-rich diet may help if malnutrition is present.
- Iron supplementation should be avoided despite the low ferritin, as the elevated serum iron indicates the body already has excess circulating iron. Some key points to consider in the management of this condition include:
- Regular monitoring of iron studies every 3-6 months is advised until values normalize.
- Phlebotomy can be an effective treatment option to reduce iron stores, with a target serum ferritin level of 50-100 lg/L, as recommended by the EASL clinical practice guidelines on haemochromatosis 1.
- MRI can be a useful diagnostic tool to detect and quantify iron overload in the liver, spleen, pancreas, heart, and brain, and to study the distribution of iron in these organs 1. The pattern of elevated iron and saturation with low ferritin and transferrin occurs because liver damage impairs the production of transferrin (the iron transport protein) while also reducing ferritin production (the iron storage protein).
- Meanwhile, iron released from damaged liver cells increases serum iron levels.
- In some cases, this pattern may also indicate hemolysis, where red blood cells are being destroyed, releasing iron into circulation. A hematology consultation may be warranted if the cause remains unclear after initial evaluation, and phlebotomy should be performed weekly (or fortnightly) until iron stores are depleted, with a target serum ferritin level of 50 lg/L, but not lower to avoid iron deficiency, as recommended by the EASL clinical practice guidelines on haemochromatosis 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Elevated Iron and Saturation with Low Ferritin and Transferrin
- Elevated iron and saturation levels can be indicative of iron overload, while low ferritin and transferrin levels may suggest iron deficiency or other underlying conditions 2.
- However, ferritin is also an acute-phase protein, and its levels can be elevated in inflammation and infection, making it a less reliable marker for iron status in certain cases 3, 4.
- In patients with hemodialysis, high serum ferritin and low iron saturation ratio can be associated with inflammation rather than iron overload 4.
- The diagnostic accuracy of ferritin concentrations for detecting iron deficiency and overload can be affected by various factors, including age, clinical status, and presence of inflammation 3.
Possible Causes and Associations
- Iron overload disorders can be caused by a variety of conditions, including hereditary hemochromatosis, hematologic disorders, and chronic liver diseases 2.
- Elevated ferritin levels can be seen in conditions such as chronic liver disease, malignancy, infections, kidney failure, and rheumatic conditions 2.
- Low ferritin levels can be indicative of iron deficiency, while low transferrin levels can be seen in conditions such as iron overload or chronic disease 3.
Diagnostic Considerations
- Magnetic resonance imaging (MRI) and liver biopsy can be used to assess iron content and diagnose iron overload disorders 5, 2.
- Genetic testing for hereditary hemochromatosis and other conditions can help identify underlying causes of iron overload 2.
- Inflammation and other factors can affect the accuracy of ferritin and transferrin measurements, and should be considered when interpreting results 3, 4.