What does a low iron level with elevated ferritin indicate?

Laboratory Findings Indicate Anemia of Chronic Disease with Possible Functional Iron Deficiency

The laboratory values showing low serum iron (54), normal MCV (90), normal TIBC (244), low-normal transferrin saturation (22-23%), and elevated ferritin (152) most likely indicate anemia of chronic disease (ACD), possibly with a component of functional iron deficiency. 1, 2

Interpretation of Laboratory Values

• Hemoglobin 11.5 g/dL: Indicates mild anemia
• MCV 90: Normal (not microcytic as would be expected in pure iron deficiency)
• Serum iron 54: Low
• TIBC 244: Normal to low-normal (would be elevated in pure iron deficiency)
• Transferrin saturation 22-23%: Low-normal (below 20% would indicate insufficient iron for erythropoiesis)
• Ferritin 152: Elevated (above the target range of 50-100 μg/L)

Differential Diagnosis

1. Anemia of Chronic Disease (most likely)

   • Characterized by low serum iron, normal/low TIBC, and elevated ferritin 2
   • Inflammatory cytokines increase hepcidin production, which blocks iron release from stores
   • Common in chronic inflammation, autoimmune diseases, cancer, and kidney failure

2. Functional Iron Deficiency

   • Adequate iron stores (normal/high ferritin) but insufficient iron availability for erythropoiesis
   • Transferrin saturation at the lower end of normal range (22-23%) suggests this possibility 1

3. Mixed Anemia (ACD with true iron deficiency)

   • Less likely given the elevated ferritin, but possible if significant inflammation is present

Clinical Considerations

• In inflammatory conditions, ferritin levels up to 100 μg/L may still be consistent with iron deficiency 1
• The patient's ferritin of 152 exceeds this threshold, suggesting adequate iron stores
• Transferrin saturation is borderline (just above the 20% threshold that indicates insufficient iron for erythropoiesis) 1

Next Steps

1. Evaluate for underlying chronic conditions

   • Inflammatory disorders (rheumatoid arthritis, SLE, IBD)
   • Malignancy
   • Chronic infection
   • Chronic kidney disease

2. Additional laboratory tests to consider

   • Inflammatory markers (CRP, ESR)
   • Hepcidin levels (if available)
   • Complete blood count with reticulocyte count
   • Kidney function tests

Common Pitfalls to Avoid

• Misdiagnosing as pure iron deficiency: The elevated ferritin makes pure iron deficiency unlikely
• Overlooking functional iron deficiency: Despite normal/high ferritin, iron may not be available for erythropoiesis
• Ignoring underlying conditions: The anemia is likely secondary to another disorder that requires diagnosis and treatment
• Inappropriate iron supplementation: Providing iron when stores are adequate (high ferritin) may be harmful unless functional deficiency is confirmed 1

Special Considerations

• If chronic kidney disease is present, different diagnostic criteria apply - patients with high ferritin (500-1200 ng/ml) but low transferrin saturation (<25%) may still benefit from iron therapy 1, 3
• Serum ferritin iron measurement (not routinely available) might help distinguish between inflammation-induced ferritin elevation and true iron stores 4
• Recent evidence suggests that current ferritin reference ranges may underdiagnose iron deficiency, particularly in women 5