Which of the following is most consistent with iron deficiency anemia: ferritin, Erythrocyte Distribution Width (EDW), reticulocyte count, total iron, total iron binding capacity (TIBC), iron transfer, and iron saturation?

Serum Ferritin is Most Consistent with Iron Deficiency Anemia

Serum ferritin is the most powerful and specific laboratory parameter for diagnosing iron deficiency anemia, with levels below 30 μg/L being highly indicative of iron deficiency. 1

Laboratory Parameters in Iron Deficiency Anemia

Iron deficiency anemia is characterized by specific changes in various laboratory parameters:

1. Serum Ferritin:

   • Most sensitive and specific marker
   • Levels <30 μg/L indicate iron deficiency with high specificity
   • Levels <15 ng/mL have 99% specificity for iron deficiency 1
   • Directly reflects iron storage in liver, spleen, and bone marrow reticuloendothelial cells 2

2. Transferrin Saturation:

   • Typically low (<20%) in iron deficiency
   • Reflects iron readily available for erythropoiesis
   • Less specific than ferritin as it can also be low in chronic disease 2, 1

3. Total Iron Binding Capacity (TIBC):

   • Elevated in iron deficiency
   • Measures circulating transferrin
   • Can help differentiate from anemia of chronic disease (where TIBC is normal to low) 1

4. Serum Iron:

   • Low in iron deficiency
   • Also low in anemia of chronic disease, making it less specific 1

5. Red Cell Distribution Width (RDW):

   • Elevated in iron deficiency
   • Less specific as it can be affected by other conditions 1

6. Reticulocyte Count:

   • Not a primary indicator for iron deficiency diagnosis
   • May be inappropriately normal or low in iron deficiency anemia 3

Why Ferritin is Superior

Ferritin is considered the gold standard for several reasons:

• The American Gastroenterological Association recognizes serum ferritin as the most powerful test for iron deficiency 1
• When ferritin is low, it almost always indicates depleted iron stores 2
• Ferritin separated iron deficiency from anemia of chronic disease in 20 of 22 patients in comparative studies 4
• There is a strong relationship (r = 0.9625; p < 0.05) between decreasing body iron stores and falling plasma ferritin levels 5

Important Caveats

• Ferritin as an acute phase reactant: Ferritin levels may be falsely elevated in inflammatory conditions, potentially masking iron deficiency 1
• Interpretation in chronic disease: In patients with chronic inflammation, ferritin cutoff values may need to be adjusted upward (e.g., <100 ng/mL instead of <30 ng/mL) 2
• Functional iron deficiency: Patients may have normal or elevated ferritin but still respond to iron therapy due to functional iron deficiency, particularly in conditions like chronic kidney disease 2

Diagnostic Algorithm

1. Measure serum ferritin as the primary test

   • If <30 μg/L: Confirms iron deficiency
   • If 30-100 μg/L and inflammation present: Consider iron deficiency
   • If >100 μg/L: Iron deficiency unlikely

2. If ferritin results are equivocal, assess transferrin saturation

   • If <20%: Supports iron deficiency diagnosis
   • If >20%: Less likely to be iron deficiency

3. Additional supporting tests:

   • Elevated TIBC
   • Low serum iron
   • Microcytosis (low MCV)
   • Elevated RDW

Conclusion

While all the parameters mentioned have roles in diagnosing iron deficiency anemia, serum ferritin stands out as the most consistent and reliable indicator, providing the best reflection of iron stores and offering the highest diagnostic value for iron deficiency anemia.