What does a low iron level with high ferritin indicate?

Interpretation of Iron Studies: Anemia of Chronic Disease with Inflammation

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

Laboratory Findings Analysis

The pattern of abnormalities in these iron studies reveals a classic presentation:

• Low serum iron (26): Indicates reduced circulating iron
• High ferritin (242): Suggests inflammation rather than iron deficiency
• Low transferrin saturation (10%): Reflects poor iron availability for erythropoiesis
• Low transferrin (169) and TIBC (248): Characteristic of ACD, as opposed to iron deficiency where these would be elevated

This pattern strongly indicates anemia of chronic disease with inflammation, where iron is sequestered in storage sites and unavailable for red blood cell production despite adequate or increased total body iron stores 2, 1.

Distinguishing from Iron Deficiency

In pure iron deficiency:

• Ferritin would be low (<30 μg/L in non-inflammatory states)
• Transferrin and TIBC would be elevated
• Iron saturation would be low

The high ferritin with low transferrin/TIBC in this case makes absolute iron deficiency unlikely 1. However, it's important to note that:

1. In inflammatory states, ferritin acts as an acute phase reactant and can be elevated despite iron deficiency
2. According to European consensus guidelines, ferritin levels up to 100 μg/L may still represent iron deficiency in inflammatory conditions 2

Potential Underlying Causes

This pattern warrants investigation for underlying inflammatory conditions such as:

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

Recommended Next Steps

1. Measure inflammatory markers: CRP and ESR to confirm and quantify inflammation
2. Complete blood count: To assess anemia severity and red cell indices
3. Clinical evaluation: For symptoms and signs of underlying inflammatory conditions
4. Consider reticulocyte hemoglobin content: To help distinguish functional from absolute iron deficiency

Treatment Considerations

Treatment should focus on:

1. Addressing the underlying inflammatory condition: This is the primary approach to improve the anemia 1

2. Iron supplementation:

   • Oral iron is generally not beneficial in ACD and may worsen inflammation
   • Intravenous iron may be considered if functional iron deficiency is contributing to anemia

3. Monitor response: Follow hemoglobin, iron studies, and inflammatory markers to assess treatment effectiveness

Important Caveats

• In obesity, ferritin can be elevated due to low-grade inflammation rather than adequate iron stores 3
• In patients with mixed anemia (ACD + iron deficiency), diagnosis can be challenging and may require additional testing such as soluble transferrin receptor levels 4
• Transferrin saturation <16% with ferritin >100 μg/L is diagnostic of ACD in the presence of inflammation 2

Remember that treating the underlying inflammatory condition is crucial for resolving this type of anemia, as iron supplementation alone may be ineffective or even counterproductive if the primary issue is inflammation-driven iron sequestration.