High Ferritin with Normal Hemoglobin and Normal Serum Iron: Not Anemia
This laboratory pattern does not represent anemia at all, since hemoglobin is normal by definition. However, the elevated ferritin with normal serum iron suggests either an inflammatory state, chronic disease process, or iron overload condition rather than any form of iron deficiency 1.
Understanding the Laboratory Pattern
The combination of high ferritin with normal hemoglobin and normal serum iron indicates:
- No anemia is present - anemia requires hemoglobin <13 g/dL for men or <12 g/dL for women 1
- Ferritin elevation without anemia typically reflects ferritin's role as an acute-phase reactant rather than true iron overload 2
- Normal serum iron excludes active iron deficiency and suggests adequate circulating iron for erythropoiesis 2
Critical Next Step: Calculate Transferrin Saturation
You must calculate transferrin saturation (TSAT) using the formula: (serum iron × 100) ÷ total iron-binding capacity to determine the underlying condition 1, 2.
Interpretation Algorithm Based on TSAT:
If TSAT >45%: This suggests hemochromatosis or primary iron overload 3
- Proceed with genetic testing for HFE mutations (C282Y, H63D)
- Consider hepatic iron concentration assessment if ferritin chronically >1000 μg/L
- Therapeutic phlebotomy may be indicated
If TSAT 20-45% (normal range): This indicates inflammation or chronic disease 1
- Ferritin is elevated as an acute-phase reactant
- Check inflammatory markers: CRP, ESR 1
- Investigate for underlying conditions:
If TSAT <20%: This represents functional iron deficiency or anemia of chronic disease 1
- Iron is sequestered in reticuloendothelial system by hepcidin
- Diagnostic criteria: ferritin >100 μg/L with TSAT <20% in presence of inflammation 1
- Iron is stored but not available for erythropoiesis 1
Common Clinical Scenarios
Anemia of Chronic Disease (if anemia were present)
In inflammatory conditions, cytokines upregulate hepcidin production in the liver, which reduces iron export from macrophages through ferroportin reduction, creating functional iron deficiency despite elevated ferritin 1. However, since hemoglobin is normal in this case, this represents the inflammatory state without yet causing anemia 1.
Inflammatory Iron Block
Ferritin >100 μg/L with normal hemoglobin suggests chronic inflammation without significant erythropoietic suppression yet 1. The elevated ferritin reflects:
- Increased synthesis as an acute-phase protein 2
- Iron sequestration in macrophages 1
- Potential early stage before anemia develops 1
Critical Pitfalls to Avoid
- Never assume elevated ferritin alone indicates iron overload - ferritin rises with inflammation, infection, or tissue damage independently of iron status 2, 3
- Do not initiate therapeutic phlebotomy without confirming elevated transferrin saturation - phlebotomy is contraindicated when TSAT is normal or low 3
- Recognize that ferritin can mask true iron deficiency when inflammation is present - a patient can have depleted iron stores despite "normal" or elevated ferritin if inflammation is driving ferritin up 1
Recommended Workup
Immediate laboratory tests needed:
- Complete iron panel including TIBC to calculate TSAT 1, 2
- Inflammatory markers: CRP, ESR 1
- Complete blood count with MCV and reticulocyte count 1
- Comprehensive metabolic panel for liver and kidney function 3
If TSAT >45% or ferritin >300 μg/L:
- HFE genetic testing for hemochromatosis 3
- Hepatitis B and C serologies if liver enzymes elevated 3
- Consider imaging for hepatic assessment 3
If inflammatory markers elevated:
- Age-appropriate cancer screening 3
- Evaluation for chronic liver disease, autoimmune conditions, chronic infections 1, 3
Monitoring Strategy
Recheck ferritin, complete iron panel, and inflammatory markers in 3-6 months to assess trajectory 3. If ferritin rises above 500 μg/L or TSAT increases above 45%, intensify investigation including possible liver biopsy for hepatic iron concentration if hemochromatosis is suspected 3.