Which statement about serum ferritin (a protein that stores iron) is true: is it synonymous with transferrin (a protein that binds iron), a better test for bone marrow iron stores than a Prussian blue stain of marrow particles, a sensitive indicator of iron deficiency, or specific for hemochromatosis (a condition of iron overload)?

Serum Ferritin and Iron Status Assessment

Serum ferritin is a sensitive indicator of iron deficiency, with low levels having high specificity for iron deficiency, making option C the correct answer. 1, 2

Characteristics of Serum Ferritin

• Serum ferritin is an intracellular protein that circulates in small amounts in plasma
• Under normal conditions, there is a direct relationship between serum ferritin concentration and body iron stores, with 1 μg/L of serum ferritin equivalent to approximately 10 mg of stored iron 1
• Serum ferritin is NOT synonymous with transferrin (option A is incorrect) - transferrin is a separate protein that binds and transports iron in the bloodstream 1, 2

Serum Ferritin as an Indicator of Iron Deficiency

• Serum ferritin is the earliest and most specific indicator of depleted iron stores, especially when used with other iron status tests 1
• Low serum ferritin levels (<15 μg/L) have a specificity of 98-100% for iron deficiency 1, 2
• Serum ferritin is more sensitive than hemoglobin for detecting early iron deficiency 2

Comparison with Bone Marrow Assessment

• While bone marrow examination with Prussian blue staining is considered the gold standard for assessing iron stores, serum ferritin is NOT better than bone marrow assessment (option B is incorrect) 3, 4
• Research shows that bone marrow examination remains the most sensitive test for diagnosing iron deficiency in hospitalized patients 3
• However, serum ferritin correlates well with bone marrow iron stores and provides a less invasive alternative 5, 6

Limitations of Serum Ferritin

• Serum ferritin is an acute phase reactant - levels can be elevated in inflammation, infection, liver disease, malignancy, and other conditions independent of iron status 1, 2
• In inflammatory conditions, ferritin may be elevated despite actual iron deficiency 2
• In chronic inflammatory diseases, higher cutoff values (up to 100 μg/L) are recommended to diagnose iron deficiency 1, 2

Serum Ferritin and Hemochromatosis

• Elevated serum ferritin is NOT specific for hemochromatosis (option D is incorrect) 7
• While serum ferritin is elevated in hemochromatosis, many other conditions can cause elevated ferritin levels 2, 7
• The correlation between serum ferritin and total body iron burden in hemochromatosis exists but is not very strong, even in patients homozygous for the C282Y mutation 7

Clinical Application

• For accurate assessment of iron status, combine ferritin measurement with other parameters such as transferrin saturation, serum iron, and total iron binding capacity 2
• In patients with chronic inflammation, consider using higher ferritin cutoffs and additional markers like soluble transferrin receptor 1, 2
• Reticulocyte hemoglobin content may provide additional information about functional iron deficiency 2, 6