Iron Deficiency with Iron-Deficient Erythropoiesis
These laboratory values indicate iron deficiency with iron-deficient erythropoiesis (functional iron deficiency) in this 40-year-old woman with surgical menopause, requiring investigation of the underlying cause and consideration of iron supplementation.
Laboratory Interpretation
The transferrin saturation of 15% is below the diagnostic threshold of 16-20% that confirms iron deficiency, indicating insufficient iron available for red blood cell production despite the hemoglobin being in the low-normal range 1, 2. This pattern specifically represents iron-deficient erythropoiesis (Grade II iron deficiency), where the bone marrow lacks adequate available iron to produce hemoglobin optimally 3.
Key Diagnostic Features
Low transferrin saturation (15%): This falls below the 16% threshold used to confirm iron deficiency in adults without inflammation, and well below the normal range of 20-50% 4, 1, 2
Elevated transferrin (313 mg/dL): This is within or slightly above the normal range of 200-400 mg/dL, indicating the body is compensating by producing more transferrin to capture available iron 4, 2
Near-normal hemoglobin (13.1 g/dL): While this is at the lower end of normal for women (12.0-15.5 g/dL), it indicates the patient has not yet progressed to frank iron deficiency anemia (Grade III), but is at significant risk 4, 3
Clinical Significance in Surgical Menopause
This patient's iron deficiency is particularly concerning because surgical menopause eliminates menstrual blood loss as a cause, mandating investigation for other sources of iron loss. 2
The combination of low transferrin saturation with near-normal hemoglobin represents a critical window for intervention before progression to overt anemia 3. In premenopausal women, menstrual losses typically account for iron deficiency, but surgical menopause removes this explanation 2.
Required Next Steps
Essential Additional Testing
Serum ferritin: This is the critical missing piece to quantify iron stores and distinguish between absolute iron deficiency (ferritin <30 ng/mL) versus functional iron deficiency (ferritin 30-100 ng/mL with inflammation) 1, 2
Complete blood count with red cell indices: Obtain MCV to assess for microcytosis, which would support iron deficiency anemia if present 4, 2
C-reactive protein: Measure to assess for inflammation, which can affect ferritin interpretation and may indicate functional iron deficiency 2
Investigate Underlying Causes
Given the absence of menstrual blood loss, the following must be evaluated 2:
- Gastrointestinal blood loss: Perform fecal occult blood testing and consider endoscopy if positive or if other GI symptoms present
- Dietary assessment: Evaluate for restrictive diets, vegetarianism, or inadequate iron intake
- Malabsorption: Consider celiac disease screening, H. pylori testing, or assessment for inflammatory bowel disease
- NSAID use: Document chronic NSAID use causing occult GI bleeding
- Blood donation history: Assess frequency of blood donations
Treatment Considerations
Iron supplementation should be initiated once the underlying cause is identified, with a goal of achieving transferrin saturation ≥20% to ensure adequate iron for erythropoiesis. 1
Supplementation Strategy
Oral iron therapy: Start with 100-200 mg elemental iron daily if no contraindications exist and GI absorption is intact 2
Intravenous iron: Consider if oral iron is not tolerated, malabsorption is present, or rapid repletion is needed 1
Monitoring: Recheck iron parameters (ferritin, transferrin saturation) and CBC 4-8 weeks after initiating therapy 1
Important Clinical Pitfalls
Do not dismiss near-normal hemoglobin: The transferrin saturation of 15% indicates the patient is already in Grade II iron deficiency with compromised erythropoiesis, even though anemia has not yet developed 3
Surgical menopause mandates investigation: Unlike premenopausal women where menstrual losses explain most iron deficiency, this patient requires thorough evaluation for pathologic causes of iron loss 2
Avoid relying on transferrin saturation alone: Ferritin measurement is essential to complete the diagnostic picture and guide treatment intensity 1, 2
Account for inflammation: If inflammation is present (elevated CRP), ferritin up to 100 ng/mL may still represent iron deficiency despite seemingly "normal" levels 1, 2