Diagnosis: Functional Iron Deficiency
This patient has functional iron deficiency (FID), characterized by severely low transferrin saturation (3%) despite normal-range ferritin (93 ng/mL), indicating inadequate iron availability for erythropoiesis despite adequate iron stores. 1
Laboratory Interpretation
The key diagnostic features are:
- Hemoglobin 8.1 g/dL: Moderate anemia requiring treatment 1
- Serum iron 7 µg/dL: Severely depleted circulating iron 1
- Ferritin 93 ng/mL: Normal-range storage iron, ruling out absolute iron deficiency 1
- TIBC 263 µg/dL: Normal to low-normal iron-binding capacity 1
- Transferrin saturation 3%: Critically low (normal >20%), confirming iron-deficient erythropoiesis 1
The discordance between normal ferritin and severely low transferrin saturation defines functional iron deficiency, where iron cannot be mobilized from stores rapidly enough to support red blood cell production 1. This differs from absolute iron deficiency, which would show ferritin <100 ng/mL with transferrin saturation <20% 1.
Underlying Cause Investigation
Before initiating treatment, investigate the underlying etiology:
- Inflammatory conditions: Check CRP/ESR, as inflammation causes hepcidin upregulation that blocks iron release from stores 1
- Chronic kidney disease: Assess renal function (GFR), as CKD commonly causes FID 1
- Chronic heart failure: Evaluate cardiac function if clinically indicated 1
- Gastrointestinal blood loss: Consider upper and lower endoscopy to exclude occult bleeding, particularly in men and postmenopausal women 1, 2
- Helicobacter pylori: Test and eradicate if present, as it impairs iron uptake 1
- Inflammatory bowel disease: Evaluate if diarrhea or abdominal symptoms present 1
Treatment Approach
Initial Therapy: Oral Iron Trial
Start with oral ferrous sulfate 200 mg twice daily (or lower doses if better tolerated) for 4 weeks 1. Alternative formulations include ferrous fumarate or ferrous gluconate if ferrous sulfate is not tolerated 1.
Assess response at 4 weeks:
- Responders (hemoglobin increase ≥1.0 g/dL): Continue oral iron for 3 months total after correction to replenish stores 1, 3
- Non-responders (hemoglobin increase <1.0 g/dL): Transition to intravenous iron 1, 3
Intravenous Iron Indications
Switch to IV iron if:
- No hemoglobin response after 4 weeks of oral therapy 1, 3
- Gastrointestinal intolerance to oral iron 1
- Malabsorption conditions (celiac disease, IBD, post-gastric surgery) 1
- Chronic kidney disease on dialysis 1
- Chronic heart failure (where IV iron shows prognostic benefit) 1
IV iron options include:
- Ferric carboxymaltose: 1000 mg over 15 minutes (most convenient, single-dose capable) 1
- Iron sucrose: 200 mg over 10 minutes (requires multiple doses) 1
- Iron dextran: 20 mg/kg over 6 hours (higher anaphylaxis risk 0.6-0.7%) 1
Monitoring
Recheck complete blood count and iron studies 8-10 weeks after initiating treatment 1. Do not recheck earlier after IV iron, as ferritin will be falsely elevated 1.
Target goals:
- Hemoglobin >11-12 g/dL 1
- Transferrin saturation >20% 1
- Ferritin 100-800 ng/mL (depending on underlying condition) 1
Critical Pitfalls
Do not supplement iron if ferritin is normal without confirming transferrin saturation is low, as iron overload can occur 1. However, this patient's 3% transferrin saturation clearly indicates iron-deficient erythropoiesis requiring treatment 1.
Distinguish functional iron deficiency from inflammatory iron block: In inflammatory block, ferritin rises abruptly with sudden TSAT drop, whereas in FID, ferritin gradually decreases during treatment while remaining >100 ng/mL 1. If uncertain, trial 8-10 doses of weekly IV iron (50-125 mg); lack of response suggests inflammatory block 1.
In chronic kidney disease, different thresholds apply: Absolute iron deficiency is defined as transferrin saturation ≤20% with ferritin ≤100 ng/mL (predialysis/peritoneal dialysis) or ≤200 ng/mL (hemodialysis) 1.