From the Guidelines
The patient's iron studies, showing hyperferritinemia (ferritin 1041) with normal serum iron (13) and low iron saturation (9), are most likely indicative of an inflammatory condition rather than iron overload. This pattern is commonly seen in anemia of chronic disease (also called anemia of inflammation) 1. The key to interpreting these results lies in understanding that ferritin is an acute phase reactant that can be elevated in response to inflammation, independent of iron status.
Key Points to Consider:
- The elevated ferritin level does not necessarily indicate iron overload but could be a response to an underlying inflammatory process.
- The normal serum iron and low iron saturation suggest that the body is sequestering iron, a common response to inflammation, mediated by hepcidin.
- The management should focus on identifying and treating the underlying cause of inflammation, which could include infections, autoimmune disorders, malignancies, or chronic kidney disease.
- Additional testing, such as complete blood count, C-reactive protein, and erythrocyte sedimentation rate, should be performed to assess the severity of inflammation.
- Iron supplementation is generally not recommended as it may not be effectively utilized and could potentially worsen iron overload in tissues.
- In cases where anemia is significant and impacting quality of life, erythropoiesis-stimulating agents may be considered in conjunction with treating the underlying condition 1. The guidelines for managing conditions like HFE hemochromatosis, as outlined in the EASL clinical practice guidelines 1, emphasize the importance of phlebotomy in patients with evidence of iron overload. However, in this case, the low iron saturation and normal serum iron levels suggest that the primary issue is not iron overload but rather an inflammatory process. Therefore, the management approach should differ from that recommended for HFE hemochromatosis, focusing instead on addressing the underlying inflammation.
From the Research
Interpretation of Iron Studies
The provided iron studies show:
- Iron: 13
- Ferritin: 1041
- Iron saturation: 9
- Transferrin: 95
- TIBC: 140
These results indicate hyperferritinemia (elevated ferritin) with normal serum iron and low iron saturation.
Possible Causes of Hyperferritinemia
Hyperferritinemia can be caused by various conditions, including:
- Iron overload disorders 2
- Chronic liver disease 2, 3
- Malignancy 2
- Infections 2
- Kidney failure 2
- Rheumatic conditions, such as adult-onset Still's disease or hemophagocytic lymphohistiocytosis 2
- Hematologic disorders, such as thalassemia syndromes, myelodysplastic syndrome, myelofibrosis, sideroblastic anemias, sickle cell disease, or pyruvate kinase deficiency 2, 4, 3
Diagnostic Approach
To evaluate hyperferritinemia, the following steps can be taken:
- Confirmatory homeostatic iron regulator (HFE) genetic testing for C282Y and H63D mutations, which are commonly encountered in hereditary hemochromatosis 2
- Magnetic resonance imaging with quantitative assessment of iron content or liver biopsy to assess liver iron content 2, 3
- Consider secondary causes of iron overload if HFE genetic testing is negative for the C282Y homozygous or C282Y/H63D compound heterozygous mutations 2
Management
Management of hyperferritinemia depends on the underlying cause. In cases of iron overload, iron chelation therapy may be effective in reducing ferritin levels and improving clinical outcomes 5, 4.
Key Points
- Hyperferritinemia can be caused by various conditions, including iron overload disorders, chronic liver disease, and hematologic disorders.
- A diagnostic approach should include confirmatory HFE genetic testing, magnetic resonance imaging, and liver biopsy to assess liver iron content.
- Management of hyperferritinemia depends on the underlying cause, and iron chelation therapy may be effective in reducing ferritin levels and improving clinical outcomes 5, 2, 4, 6, 3