From the Guidelines
Elevated ferritin levels should be evaluated with additional testing to determine the underlying cause, prioritizing the assessment of iron overload conditions and inflammatory causes, as excessive iron can damage organs including the liver, heart, and pancreas, potentially leading to cirrhosis, cardiomyopathy, diabetes, and arthropathy if left untreated 1.
Evaluation of Ferritin Elevation
To evaluate ferritin elevation, the following steps should be taken:
- Check serum iron, total iron binding capacity (TIBC), and transferrin saturation to distinguish between iron overload conditions and inflammatory causes.
- If transferrin saturation is high (>45%), consider hereditary hemochromatosis and order genetic testing for HFE gene mutations 1.
- For persistently high ferritin with normal transferrin saturation, investigate inflammatory conditions, liver disease, malignancy, and metabolic syndrome.
Treatment of Ferritin Elevation
Treatment depends on the cause:
- Therapeutic phlebotomy for hemochromatosis (removing 500mL of blood every 1-2 weeks until ferritin normalizes, then maintenance phlebotomies 2-4 times yearly) 1.
- Addressing underlying conditions for secondary causes.
- Lifestyle modifications (limiting alcohol, weight loss, managing diabetes) for metabolic causes.
Importance of Monitoring
Regular monitoring of ferritin levels is essential during treatment to ensure normalization and prevent complications, as iron overload can lead to significant morbidity and mortality if left untreated 1.
Diagnostic Considerations
In patients with suspected iron overload, MRI can be helpful for detection, non-invasive quantification of iron, and to study the distribution of iron in the liver, spleen, pancreas, heart, and brain 1. In patients with inflammation, the lower limit of serum ferritin consistent with normal iron stores should be increased to 100 μg/L, and hypoferraemia should be considered likely if TfS is < 16% and serum ferritin is between 30 and 100 g/L 1.
From the Research
Causes of Ferritin Elevation
- Ferritin elevation, also known as hyperferritinemia, can be caused by various conditions, including non-human immunodeficiency virus infection, solid tumor, liver dysfunction, renal failure, and hematological malignancy 2
- The most frequent cause of hyperferritinemia is non-human immunodeficiency virus infection, followed by solid tumor, liver dysfunction, renal failure, and hematological malignancy 2
- Hyperferritinemia can also be caused by acute phase reactions and reactive increases in ferritin due to underlying conditions, with only 10% of cases related to an iron overload 3
Diagnosis and Management of Hyperferritinemia
- Differentiation of the presence or absence of an associated iron overload upon hyperferritinemia is essential, although often proves to be complex 3
- An algorithm for the diagnostic workup and management of hyperferritinemia is proposed, and general principles regarding the treatment of iron overload are discussed 3
- Treatment of hyperferritinemia should be individualized, and may be influenced by the presence of other features of iron overload 4
Treatment Options for Iron Overload
- Deferasirox, an oral iron chelator, has been shown to be effective in reducing iron burden in patients with iron overload secondary to hereditary hemochromatosis 5
- Phlebotomy is also a treatment option for iron overload, and has been compared to deferasirox in a prospective randomized trial in pediatric patients with thalassemia major following curative stem cell transplantation 6
- Deferasirox treatment or phlebotomy reduces iron burden in pediatric patients with β-thalassemia major post-HSCT, with a manageable safety profile 6