Diagnosis: Early Iron Deficiency Anemia
This presentation of low reticulocyte count, normal ferritin, and high TIBC is most consistent with early iron deficiency anemia (IDA), where iron stores are being depleted but inflammation is absent. 1
Laboratory Pattern Analysis
The combination of findings indicates:
High TIBC (elevated total iron-binding capacity) reflects the body's attempt to capture more circulating iron by increasing transferrin production, which is the hallmark of true iron deficiency 1, 2
Normal ferritin in the absence of inflammation suggests iron stores are not yet completely depleted, but are insufficient to support erythropoiesis. Ferritin <30 μg/L confirms iron deficiency without inflammation, but values up to 45 μg/L may still represent iron deficiency 1
Low reticulocyte count indicates the bone marrow cannot respond appropriately to anemia due to insufficient iron for hemoglobin synthesis, excluding hemolysis and confirming a deficiency state 1
Differential Diagnosis Considerations
Rule out anemia of chronic disease (ACD): This is critical because ACD presents with low iron but normal or low TIBC (not high), and ferritin is typically elevated (>100 μg/L) 1. Your patient's high TIBC effectively excludes ACD 1, 2.
Check inflammatory markers: Obtain CRP and ESR to confirm absence of inflammation. If CRP is elevated, ferritin cutoffs shift upward—ferritin up to 100 μg/L may still indicate iron deficiency in inflammatory states 1.
Consider thalassemia trait: If microcytosis is present with normal iron studies after treatment, obtain hemoglobin electrophoresis, particularly in appropriate ethnic backgrounds 1.
Essential Additional Workup
Complete the minimum anemia evaluation:
- Complete blood count with indices: MCV, MCH, and RDW to assess microcytosis and red cell size variability 1
- Transferrin saturation: Values <16% support iron deficiency 1
- Serum iron level: Expected to be low in iron deficiency 1, 2
- Inflammatory markers: CRP to interpret ferritin accurately 1
Identify the Underlying Cause
In adult men and postmenopausal women, assume gastrointestinal blood loss until proven otherwise 1, 2. Investigation priorities include:
- Upper and lower GI endoscopy: Essential to exclude malignancy, particularly in men with Hb <12 g/dL or postmenopausal women with Hb <10 g/dL 1
- Coeliac serology (tissue transglutaminase antibody): Malabsorption is a common cause, with ~5% pretest probability in IDA 1
- Medication review: NSAIDs and aspirin are frequent culprits 1
- Dietary assessment: Evaluate for inadequate iron intake 1, 3
In premenopausal women: Menstrual blood loss is the most common cause, but GI investigation is still warranted if anemia persists despite iron replacement 1, 2.
Management Approach
Initiate oral iron supplementation immediately while investigating the underlying cause 1:
- Standard oral iron therapy (e.g., ferrous sulfate 200 mg three times daily) is first-line 1
- Monitor response with repeat hemoglobin at 2-4 weeks; reticulocyte count should rise within 7-10 days 1
- Continue iron for 3-6 months after hemoglobin normalizes to replenish stores 1
Consider intravenous iron if:
- Oral iron is not tolerated or ineffective 1
- Malabsorption is documented 1
- Rapid correction is needed 1
Common Pitfalls to Avoid
Do not assume normal ferritin excludes iron deficiency: Ferritin is an acute phase reactant and can be falsely normal or elevated in inflammation, liver disease, or malignancy 1. Always interpret ferritin in the context of inflammatory markers and TIBC 1.
Do not overlook dual pathology: Up to 10% of patients have bleeding sources in both upper and lower GI tracts, particularly in older patients 1.
Do not stop at iron replacement alone: Failure to identify and treat the underlying cause (especially occult malignancy) leads to recurrent anemia and missed diagnoses 1, 3.