What is the diagnosis and appropriate management for a patient with low iron and high ferritin levels?

Diagnosis and Management of Anemia with Low Iron and High Ferritin

Based on the laboratory values provided (iron 14, ferritin 621, TIBC 98, transferrin 70, and transferrin saturation 14.3%), this patient has anemia of chronic disease (ACD), likely with a component of functional iron deficiency. Treatment should include intravenous iron supplementation while investigating and treating the underlying inflammatory condition.

Interpretation of Laboratory Values

• The combination of low serum iron (14), high ferritin (621), low transferrin saturation (<16%), and low TIBC (98) is diagnostic of anemia of chronic disease (ACD), also known as anemia of inflammation 1
• In ACD, inflammatory cytokines increase hepcidin production, which blocks iron absorption from the gut and prevents iron release from macrophages, leading to functional iron deficiency despite adequate or elevated iron stores 1, 2
• The transferrin saturation of 14.3% (below 16%) indicates inadequate iron availability for erythropoiesis despite the elevated ferritin 1
• The high ferritin (621) reflects an acute-phase reaction during inflammation rather than true iron sufficiency 1

Diagnostic Algorithm

1. Confirm inflammatory status:

   • Measure inflammatory markers (CRP, ESR) to confirm the presence of inflammation 1
   • When inflammation is present, ferritin levels >100 μg/L with transferrin saturation <16% are consistent with ACD 1

2. Rule out mixed deficiency:

   • Consider measuring soluble transferrin receptor (sTfR) if available - this would be high in true iron deficiency but normal or low in pure ACD 1
   • Evaluate reticulocyte hemoglobin concentration if available - a value <30 pg is predictive of response to IV iron 1

3. Investigate underlying causes:

   • Common causes include chronic infections, autoimmune disorders, inflammatory bowel disease, heart failure, chronic kidney disease, and malignancies 1, 2
   • Evaluate for occult blood loss, especially with gastrointestinal disorders 1, 3

Treatment Recommendations

1. Primary approach:

   • Intravenous iron supplementation is recommended as the first-line treatment for this patient with ACD and low transferrin saturation 1
   • Oral iron is likely to be ineffective due to hepcidin-mediated blockade of intestinal absorption during inflammation 1, 3

2. Specific IV iron protocol:

   • IV iron preparations such as iron sucrose or ferric carboxymaltose have shown efficacy in clinical trials for ACD 1
   • Dosing should be calculated based on body weight and hemoglobin deficit 1

3. Monitoring response:

   • Reassess hemoglobin, iron studies, and inflammatory markers 4-6 weeks after treatment 1
   • Expect improvement in hemoglobin levels by 1-2 g/dL with successful treatment 1

4. Additional considerations:

   • Treat the underlying inflammatory condition to address the root cause of ACD 1, 2
   • Erythropoiesis-stimulating agents may be considered if response to IV iron alone is inadequate 1, 3
   • Red blood cell transfusions should be reserved for severe symptomatic anemia 1

Important Caveats

• Avoid oral iron supplementation as monotherapy, as it is typically ineffective in ACD and may worsen inflammation 4, 3
• Transferrin saturation levels >800 μg/L are considered toxic and should be avoided during treatment 1
• Long-term monitoring is essential as recurrence of anemia is common (>50% after 1 year) 1
• In patients with heart failure and ACD, IV iron has been shown to improve functional capacity and quality of life independent of anemia correction 1