What are the implications of elevated ferritin (iron storage protein) levels, low iron (hypoferritinemia), and low transferrin (hypotransferrinemia)?

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Last updated: April 13, 2025View editorial policy

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Differential Diagnosis for High Ferritin, Low Iron, Low Transferrin

  • Single Most Likely Diagnosis
    • Anemia of Chronic Disease (ACD): This condition is characterized by high ferritin levels due to inflammation, low iron levels due to sequestration, and low transferrin levels due to decreased production in response to inflammation. ACD is a common cause of anemia in patients with chronic diseases such as rheumatoid arthritis, chronic infections, and malignancies.
  • Other Likely Diagnoses
    • Inflammatory Conditions: Conditions like rheumatoid arthritis, lupus, and other autoimmune diseases can cause elevated ferritin levels due to inflammation, while iron and transferrin levels may be low due to the body's response to chronic inflammation.
    • Chronic Kidney Disease: Patients with chronic kidney disease may have elevated ferritin levels due to inflammation and decreased iron and transferrin levels due to impaired kidney function.
    • Liver Disease: Certain liver conditions, such as non-alcoholic fatty liver disease (NAFLD), can cause elevated ferritin levels, while iron and transferrin levels may be low due to impaired liver function.
  • Do Not Miss Diagnoses
    • Hemophagocytic Lymphohistiocytosis (HLH): This rare but life-threatening condition is characterized by excessive immune activation, which can lead to elevated ferritin levels (>500 ng/mL). It is crucial to consider HLH in patients with high ferritin levels, as prompt treatment is essential.
    • Sepsis: Sepsis can cause elevated ferritin levels due to inflammation, while iron and transferrin levels may be low due to the body's response to infection. Early recognition and treatment of sepsis are critical to prevent mortality.
  • Rare Diagnoses
    • Hereditary Hemochromatosis: Although this genetic disorder typically presents with high iron and transferrin saturation, some cases may have elevated ferritin levels with low iron and transferrin levels due to the body's attempt to regulate iron overload.
    • Porphyria Cutanea Tarda: This rare genetic disorder can cause elevated ferritin levels due to iron overload, while iron and transferrin levels may be low due to the body's impaired ability to regulate iron metabolism.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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