From the Guidelines
Elevated ferritin levels require immediate investigation to determine the underlying cause, with a focus on identifying potential iron overload disorders, inflammation, liver disease, or other conditions that may impact morbidity, mortality, and quality of life. The diagnostic approach should involve confirming the elevation with repeat testing and assessing for common causes, including iron overload disorders (hemochromatosis), inflammation, liver disease, alcohol use, metabolic syndrome, and certain medications. Initial workup should include:
- Complete blood count
- Liver function tests
- Iron studies (serum iron, total iron binding capacity, transferrin saturation)
- Inflammatory markers like C-reactive protein If transferrin saturation is elevated (>45%), genetic testing for hereditary hemochromatosis should be considered, as recommended by the American Association for the Study of Liver Diseases 1.
For confirmed iron overload, therapeutic phlebotomy may be indicated, removing one unit of blood (approximately 500 mL) weekly until ferritin normalizes, then maintenance phlebotomy every 2-4 months, as supported by the 2011 practice guideline by the American Association for the Study of Liver Diseases 1. Patients with non-iron related causes should have the underlying condition addressed. Lifestyle modifications, including limiting alcohol, maintaining a healthy weight, and managing diabetes, can help reduce ferritin in metabolic causes. Regular monitoring is important, with frequency determined by the severity of elevation and underlying cause.
It is essential to note that ferritin serves as an acute phase reactant and iron storage protein, so its elevation can reflect either inflammation or true iron overload, making proper diagnostic workup essential for appropriate management, as highlighted in the EASL clinical practice guidelines on haemochromatosis 1. MRI can be a helpful tool in detecting and quantifying iron overload, particularly in patients with suspected iron overload disorders, as it provides non-invasive quantification of iron in the liver, spleen, pancreas, heart, and brain 1.
In patients with elevated ferritin levels, it is crucial to consider the potential for iron overload and its associated risks, including organ damage and increased morbidity and mortality. Therefore, a thorough diagnostic evaluation and appropriate management are necessary to improve outcomes and quality of life. The most recent and highest quality study, the EASL clinical practice guidelines on haemochromatosis 1, provides a comprehensive approach to the diagnosis and management of iron overload disorders, emphasizing the importance of early detection and treatment to prevent long-term complications.
From the Research
Raised Ferritin: Causes and Treatment
- Raised ferritin levels can be caused by various factors, including iron overload, acute phase reactions, and underlying conditions such as inflammation, metabolic syndrome, and liver disease 2, 3.
- Iron overload can lead to serious complications, including damage to organs such as the liver and endocrine glands 4, 5.
- Treatment for iron overload typically involves iron chelation therapy, which can help reduce iron levels and prevent organ damage 4, 5, 6.
Iron Chelation Therapy
- Iron chelators, such as deferoxamine, deferiprone, and deferasirox, are used to treat iron overload 4, 5, 6.
- Each of these iron chelators has its own advantages and disadvantages, and combination therapy may be a promising approach 4, 6.
- Deferasirox, an oral iron chelator, has been shown to be effective in reducing iron burden in patients with transfusional hemosiderosis 5.
Diagnosis and Management of Hyperferritinemia
- Hyperferritinemia can be diagnosed through laboratory tests, including ferritin levels and transferrin saturation 2, 3.
- A diagnostic algorithm can be used to identify the cause of hyperferritinemia and rule out hepatic iron overload 3.
- Treatment for hyperferritinemia depends on the underlying cause, and may involve iron chelation therapy, phlebotomy, or other treatments 2, 3.