Medical Analysis

Understanding Ferritin: The Crucial Cellular Iron Storage Repository

Ferritin is found in virtually all cells of the body and serves as the cellular storage repository for iron. It is a macromolecule with an average molecular weight of near 440 kD that varies depending on the iron content. The majority of ferritin iron stores are found in the liver, spleen, and bone marrow. Ferritin is present in small concentrations and correlates with total-body iron stores, making its measurement valuable for the assessment of disorders of iron metabolism.

Serum Ferritin Test: Clinical Insights and Diagnostic Utility

The serum ferritin test reflects and provides supportive evidence of iron deficiency and body iron stores. It is performed for the same purpose in various disorders. The only drawback is that it is an acute phase reactant and hence shows an increase in inflammatory conditions, which we need to take into account before giving respect to its value for iron deficiency.

Primary Clinical Indications for Ferritin Testing

The test is indicated for several conditions, including iron deficiency anemia and liver diseases, as much of the ferritin is stored in the liver. It is also used to monitor iron therapy and investigate restless legs syndrome or burning sensations in legs. Furthermore, it is essential for diagnosing iron overload, such as hemochromatosis and haemosiderosis, as well as Adult onset Still Disease (AOSD). Additionally, clinicians use it to monitor chronic (long-lasting) conditions that may affect iron levels, such as cancer, renal diseases, and autoimmune diseases.

Laboratory Procedures for Ferritin Assessment

Sample Collection and Preparation

No preparation is needed before sample collection. For the procedure, collect 3.0 mL of blood in a plain tube (red-capped). Separate serum as early as possible and send it to the lab. Samples in lavender (K2EDTA or K3EDTA), pink (K2EDTA), or green (lithium heparin) are also accepted, and one must separate plasma as early as possible before sending to the lab.

Established Methods of Estimation

Several established laboratory methods exist for estimating ferritin, including:

• Chemiluminescent immunoassay (ICMA)

• Nephelometry (Turbidimetry)

• Enzyme-linked Immunoabsorbent assay (ELISA)

• Immunoradiometric Assay

• Radioimmunoassay

Comprehensive Reference Range for Serum Ferritin

Ferritin and Iron Metabolism Markers: Clinical Correlations

For Non-Medicos: Understanding Diagnostic Trends and Limitations

Factors Influencing Ferritin Levels

Causes of increased ferritin include inflammatory bowel disease, chronic inflammation, SLE, repeated blood transfusions, tuberculosis, insulin resistance, rheumatoid arthritis, hemochromatosis, haemosiderosis, non-alcoholic fatty liver disease, hepatitis, and obesity. Conversely, causes of decreased ferritin include iron deficiency anemia, chronic blood loss (e.g., GI bleeding), pregnancy, chronic kidney disease, malabsorption syndrome, adrenal insufficiency, liver cirrhosis, and hypothyroidism.

Diagnostic Utility of Ferritin Trends

Important Precautions and Interpretation Limitations

When interpreting results, clinicians must rule out inflammation and infection, check CRP levels, and confirm or rule out acute illness. It is vital to look for chronic inflammatory conditions, assess liver and renal function tests, and consider any history of recent blood transfusions or iron supplement usage. One should also rule out hereditary hemochromatosis risk, use higher ferritin cut-offs if inflammation is present, and always interpret ferritin in conjunction with TSAT and TIBC.

Limitations to note: As ferritin is an acute-phase reactant, it is increased in chronic infection, acute inflammation, liver diseases, and autoimmune disorders. It is of limited use in pregnancy, as it is seen to be reduced even though bone marrow iron is within normal limits in late pregnancy. Furthermore, those patients who are receiving or just received monoclonal antibodies may show erroneous results.

References:

• Andrews, N. C. (2017). Disorders of iron metabolism. New England Journal of Medicine, 376(14), 1362-1372.

• Camaschella, C. (2019). Iron deficiency. Blood, 133(1), 30-39.

• Girelli, D., Nemeth, E., & Swinkels, D. W. (2021). Hepcidin in the diagnosis of iron disorders. Blood, 138(1), 16-25.

• Kassebaum, N. J., et al. (2020). The global burden of anemia. The Lancet Haematology, 7(2), e113-e125.

• Kobayashi, M. (2020). Ferritin: Structure, function, and importance in iron metabolism. Journal of Biological Chemistry, 295(16), 5231-5240.

• Lopez, A., et al. (2016). Iron deficiency anaemia. The Lancet, 387(10021), 907-916.

• Nemeth, E., & Ganz, T. (2021). Hepcidin-ferroportin interaction and the regulation of iron homeostasis. Annual Review of Biochemistry, 90, 715-741.

• Pasricha, S. R., et al. (2021). Iron deficiency. The Lancet, 397(10270), 233-248.

• Porter, J. B. (2019). Practical management of iron overload. British Journal of Haematology, 186(1), 20-33.

• Schrier, S. L. (2022). Approach to the adult with anemia. UpToDate.

• Tiu, J. G., et al. (2020). Adult-onset Still’s disease: A comprehensive review. Journal of Clinical Medicine, 9(6), 1957.

• Weiss, G., & Goodnough, L. T. (2015). Anemia of chronic disease. New England Journal of Medicine, 352(10), 1011-1023.

• World Health Organization. (2020). Serum ferritin concentrations for the assessment of iron status and iron deficiency in populations. WHO Vitamin and Mineral Nutrition Information System.

• Zoller, H., & Weiss, G. (2021). Iron: A global health issue. Nature Reviews Disease Primers, 7, 72.

• Zurlo, G., et al. (2020). Iron metabolism in health and disease. International Journal of Molecular Sciences, 21(9), 3123.

FAQ’s:

1. What is ferritin primarily used for?
Ferritin is a macromolecule that serves as the body’s primary cellular storage repository for iron.

2. Where is most ferritin stored?
The majority of ferritin iron stores are located in the liver, spleen, and bone marrow.

3. What does serum ferritin measure?
It measures small concentrations of ferritin in the blood to assess overall body iron stores.

4. Why is inflammation a problem?
Ferritin is an acute phase reactant, meaning levels increase during inflammation, potentially masking iron deficiency.

5. What samples are required?
Collect 3.0 mL of blood in a plain red-capped tube, separating the serum as quickly as possible.

6. Which methods estimate ferritin?
Common methods include chemiluminescent immunoassay (ICMA), ELISA, nephelometry, immunoradiometric assay, and radioimmunoassay.

7. Does pregnancy affect ferritin levels?
Yes, ferritin is of limited use in pregnancy as levels often decrease despite normal bone marrow stores.

8. What indicates iron deficiency?
Low ferritin levels combined with low serum iron and high TIBC typically indicate iron deficiency anemia.

9. What causes high ferritin?
Increased levels may result from chronic inflammation, iron overload, liver disease, or certain hematologic malignancies.

10. How is iron therapy monitored?
Clinicians monitor the trend of ferritin levels over time to measure the patient’s response to therapy.

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