What is the interpretation of iron studies showing low iron, high ferritin, low iron saturation, low transferrin, and low TIBC?

Interpretation of Iron Studies Showing Anemia of Chronic Disease with Inflammation

The iron studies showing low iron, high ferritin, normal iron saturation, low transferrin, and low TIBC are most consistent with anemia of chronic disease (ACD) with inflammation, rather than iron deficiency anemia. 1, 2

Analysis of Laboratory Values

• Iron: 29 (L) - Low serum iron is seen in both iron deficiency anemia and anemia of chronic disease
• Ferritin: 636 (H) - Significantly elevated ferritin indicates inflammation rather than iron deficiency
• Iron Saturation: 30% - Normal transferrin saturation (>16%) suggests adequate iron availability
• Transferrin: 66 (L) - Low transferrin is characteristic of anemia of chronic disease
• TIBC: 97 (L) - Low TIBC is consistent with anemia of chronic disease, not iron deficiency

Diagnostic Reasoning

1. High ferritin with low transferrin/TIBC: This pattern strongly indicates anemia of chronic disease with inflammation. In true iron deficiency, ferritin would be low (<30 μg/L in non-inflammatory states) 1, 2.

2. Normal iron saturation: Despite low serum iron, the saturation is normal (>16%) because both iron and transferrin/TIBC are proportionally reduced 1.

3. Inflammatory pattern: The European evidence-based consensus guidelines state that serum ferritin >100 μg/L with transferrin saturation <16% indicates anemia of chronic disease 1. Here we have an even higher ferritin (636) with normal saturation.

Clinical Implications

• This pattern suggests an underlying inflammatory condition that is causing:

  • Increased hepcidin production
  • Sequestration of iron in macrophages
  • Reduced iron availability for erythropoiesis despite adequate iron stores

• Common causes of this pattern include:

  • Chronic inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease)
  • Chronic infections
  • Malignancy
  • Chronic kidney disease
  • Liver disease

Management Recommendations

1. Identify and treat the underlying inflammatory condition

   • Complete history and physical examination focusing on symptoms of chronic inflammation
   • Consider measuring inflammatory markers (CRP, ESR) to confirm inflammatory state

2. Iron supplementation considerations:

   • Oral iron supplementation is unlikely to be beneficial and may worsen inflammation
   • Intravenous iron may be considered if functional iron deficiency is contributing to anemia
   • According to guidelines, IV iron may be preferred in cases of clinically active inflammatory disease 2

3. Additional testing:

   • Complete blood count with red cell indices to assess severity of anemia
   • Reticulocyte count to evaluate bone marrow response
   • Consider erythropoietin levels if chronic kidney disease is suspected

Important Caveats

• Ferritin >100 μg/L in the presence of inflammation does not rule out coexisting iron deficiency 1, 2
• In patients with chronic inflammation, higher ferritin cutoffs (up to 100 μg/L) should be used to diagnose iron deficiency 2
• The combination of high ferritin and low transferrin/TIBC makes absolute iron deficiency unlikely in this case
• Reticulocyte hemoglobin content can help distinguish functional from absolute iron deficiency 1, 2

This pattern of iron studies requires investigation of the underlying inflammatory condition causing the anemia of chronic disease, as treating this condition will likely improve the anemia.