What are the expected changes in iron studies in iron deficiency anemia?

From the Guidelines

In iron deficiency, characteristic changes in iron studies include a decrease in serum ferritin, transferrin saturation, and serum iron, along with an increase in total iron-binding capacity (TIBC) and soluble transferrin receptor (sTfR) levels, with serum ferritin levels typically falling below 30 ng/mL and transferrin saturation below 16%. These changes occur in a predictable sequence, starting with storage iron depletion (low ferritin) followed by transport iron depletion (low transferrin saturation, low serum iron, high TIBC), and ultimately affecting erythropoiesis 1. The pattern of low ferritin, low transferrin saturation, low serum iron, and high TIBC is highly specific for iron deficiency. However, it's crucial to consider that ferritin is an acute phase reactant and may be falsely elevated in inflammatory conditions, potentially masking iron deficiency, in which case additional markers like sTfR or sTfR/ferritin index may be more reliable indicators of iron status 1.

Key Changes in Iron Studies

• Decrease in serum ferritin, reflecting depleted iron stores
• Decrease in transferrin saturation, indicating reduced iron availability
• Increase in TIBC, as the body attempts to maximize iron transport capacity
• Decrease in serum iron levels, dropping below the normal range
• Increase in sTfR levels, indicating enhanced cellular demand for iron

Considerations in Inflammatory Conditions

• Ferritin may be falsely elevated due to its role as an acute phase reactant
• Additional markers like sTfR or sTfR/ferritin index may be necessary for accurate diagnosis
• In the presence of inflammation, a serum ferritin up to 100 mg/L may still be consistent with iron deficiency 1

Diagnostic Criteria

• Serum ferritin <30 mg/L is an appropriate criterion for the diagnosis of iron deficiency anemia in the absence of inflammation
• In the presence of inflammation, diagnostic criteria include a serum ferritin >100 mg/L and transferrin saturation <20% for anemia of chronic disease, and a combination of true iron deficiency and anemia of chronic disease is likely if serum ferritin is between 30 and 100 mg/L 1

From the Research

Changes in Iron Studies Expected in Iron Deficiency

The changes in iron studies expected in iron deficiency can be summarized as follows:

• Low serum ferritin levels, typically <30 ng/mL, indicating depleted iron stores 2
• Low transferrin saturation, less than 20%, indicating insufficient iron available for erythropoiesis 2, 3
• Elevated levels of soluble transferrin receptor, indicating increased demand for iron 4, 5
• Low reticulocyte hemoglobin content (CHr), indicating iron-deficient erythropoiesis 4
• Low hemoglobin levels, indicating anemia 2, 3

Diagnostic Markers

The following diagnostic markers are used to assess iron status:

• Serum ferritin, a reflection of iron stores 2, 3, 5, 6
• Transferrin saturation, a measure of iron availability 2, 3
• Soluble transferrin receptor, a marker of iron demand 4, 5
• Reticulocyte hemoglobin content (CHr), an early marker of iron-deficient erythropoiesis 4
• Hepcidin, a regulator of iron metabolism 3
• Erythroferrone, a marker of iron status 5

Interpretation of Results

The interpretation of iron studies requires consideration of the clinical context and the presence of inflammation or other conditions that may affect iron metabolism 2, 3, 5, 6. A combination of markers may be necessary to accurately diagnose iron deficiency or iron overload 5, 6.