How to manage a patient with hyperferritinemia, low transferrin saturation, normal total iron binding capacity, and iron deficiency?

From the Guidelines

Management of a patient with hyperferritinemia, low transferrin saturation, normal total iron binding capacity, and iron deficiency should prioritize addressing the iron deficiency while investigating the cause of elevated ferritin, starting with oral iron supplementation such as ferrous sulfate 325 mg daily or twice daily between meals, as the most recent and highest quality evidence is not available, but based on the provided evidence from 1, oral iron supplementation is a reasonable approach. When managing a patient with these characteristics, it is essential to consider the distinction between absolute and functional iron deficiency, as outlined in the guidelines from 1.

• The patient's low transferrin saturation and normal total iron binding capacity suggest iron deficiency, despite the elevated ferritin levels, which may be indicative of an acute phase reaction rather than iron overload.
• The guidelines from 1 emphasize the importance of distinguishing between absolute and functional iron deficiency, as well as the need to investigate the cause of elevated ferritin levels.
• In this scenario, the low transferrin saturation is a more reliable indicator of iron status than the ferritin level, as ferritin can be elevated due to concurrent inflammatory conditions, as noted in 1.
• Oral iron supplementation should be initiated, and the patient's response should be monitored with repeat hemoglobin and iron studies after 4-8 weeks of therapy.
• If the patient has persistent iron deficiency despite oral supplementation, IV iron formulations such as iron sucrose or ferric carboxymaltose may be considered, as suggested by the guidelines from 1.
• Simultaneously, it is crucial to investigate the cause of hyperferritinemia, which may include inflammation, infection, malignancy, liver disease, or metabolic disorders, and to obtain a comprehensive history and physical examination, and consider additional testing including CRP, liver function tests, and screening for hemochromatosis gene mutations if clinically indicated.

From the Research

Managing Hyperferritinemia with Low Transferrin Saturation and Iron Deficiency

• Hyperferritinemia, characterized by high serum ferritin levels, can be caused by various conditions, including iron overload, inflammation, and liver disease 2.
• In patients with hyperferritinemia, low transferrin saturation, and normal total iron binding capacity, iron deficiency is a possible diagnosis, especially if serum ferritin is <100 μg/L or transferrin saturation is <20% 3.
• The presence of iron deficiency in patients with hyperferritinemia can be due to chronic inflammatory conditions, such as chronic kidney disease, heart failure, or inflammatory bowel disease, which can lead to increased hepcidin expression and restricted iron availability 3.

Diagnostic Approach

• Serum ferritin and transferrin saturation should be assessed to diagnose iron deficiency in patients with hyperferritinemia and low transferrin saturation 4, 3.
• A serum ferritin threshold of <100 μg/L or transferrin saturation <20% can be considered diagnostic for iron deficiency in patients with chronic inflammatory conditions 3.
• If serum ferritin is 100-300 μg/L, transferrin saturation <20% is required to confirm iron deficiency 3.

Treatment Approach

• Oral iron therapy is typically first-line therapy for iron deficiency, but intravenous iron may be indicated for patients with oral iron intolerance, poor absorption, or chronic inflammatory conditions 4.
• In patients with high serum ferritin and low transferrin saturation, intravenous iron therapy may be effective in increasing hemoglobin levels, especially if reticulocyte hemoglobin content is high 5.
• The response to treatment with intravenous iron may not be predicted by baseline iron and inflammation markers, such as ferritin, soluble transferrin receptor, or C-reactive protein 5.