Diagnosis: Iron Deficiency Anemia with Possible Functional Iron Deficiency
This presentation of low RBC, hemoglobin, hematocrit, and serum iron with normal ferritin most likely represents iron deficiency anemia in the setting of inflammation or chronic disease, where ferritin is falsely elevated as an acute phase reactant. 1
Understanding the Laboratory Pattern
The combination of low iron with normal ferritin is paradoxical and requires careful interpretation:
Normal ferritin does NOT exclude iron deficiency in inflammatory states. Ferritin is an acute phase protein that rises during inflammation, masking underlying iron depletion. 1
In the presence of inflammation, ferritin levels up to 100 μg/L may still be consistent with iron deficiency. 1 This is a critical diagnostic threshold that many clinicians miss.
Without inflammation, ferritin <30 μg/L indicates iron deficiency; with inflammation, this threshold increases to <100 μg/L. 1
Essential Next Steps for Diagnosis
Immediate Laboratory Assessment Required:
Check inflammatory markers (CRP, ESR) to determine if inflammation is present and affecting ferritin interpretation 1
Measure transferrin saturation (TSAT): A TSAT <16-20% strongly suggests iron deficiency even with normal ferritin 1
Assess mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH): Microcytosis and hypochromia support iron deficiency, though these are late findings 1
Consider soluble transferrin receptor (sTfR) if available: Elevated in true iron deficiency, normal/low in anemia of chronic disease 1
Diagnostic Algorithm:
If inflammation is present (elevated CRP/ESR):
- Ferritin 30-100 μg/L + TSAT <16% = Mixed iron deficiency and anemia of chronic disease 1
- Ferritin >100 μg/L + TSAT <20% = Anemia of chronic disease 1
If no inflammation (normal CRP/ESR):
- This scenario with normal ferritin and low iron is unusual and warrants investigation for other causes including thalassemia trait, sideroblastic anemia, or laboratory error 1
Treatment Approach
Address Underlying Cause First:
Investigate for blood loss and malabsorption:
- In men and postmenopausal women, gastrointestinal evaluation with endoscopy is mandatory to exclude malignancy 1, 2
- In premenopausal women, assess for menorrhagia and consider GI evaluation if severe or refractory 1
- Check for celiac disease with serological testing 3
Iron Replacement Therapy:
Oral iron is first-line treatment:
- Initiate oral iron supplementation (e.g., ferrous sulfate 325 mg daily to three times daily) 2, 4
- Simplified once-daily dosing improves compliance 1
- Continue for 3-6 months to replenish stores, not just correct hemoglobin 2
Consider intravenous iron if:
- Oral iron is not tolerated or causes significant side effects 2, 4
- Malabsorption is present 2, 5
- Rapid correction is needed 5
- Patient fails to respond to adequate oral iron trial 2, 4
Monitor Response:
- Recheck hemoglobin in 4-6 weeks: An increase >1 g/dL confirms iron deficiency as the cause 1, 4
- If no response to oral iron, reassess diagnosis and consider parenteral therapy 2, 4
Critical Pitfalls to Avoid
Do not assume normal ferritin excludes iron deficiency. This is the most common diagnostic error in this clinical scenario. 1
Do not overlook underlying malignancy or serious GI pathology. Iron deficiency in adults (especially men and postmenopausal women) requires investigation even with mild anemia. 1, 2
Do not confuse this with anemia of chronic disease alone. The low serum iron with normal ferritin suggests functional iron deficiency where iron is sequestered but not available for erythropoiesis. 1
Check for thalassemia trait if microcytosis is disproportionate to anemia and iron studies normalize. Hemoglobin electrophoresis is indicated in appropriate ethnic backgrounds. 1