Iron Deficiency with Low Transferrin Saturation
Your patient has confirmed iron deficiency that requires immediate treatment, as indicated by a transferrin saturation of 12%—well below the diagnostic threshold of 16-20%—combined with a serum iron of 32 µg/dL. 1
Diagnostic Interpretation
Your laboratory values definitively establish iron-deficient erythropoiesis:
- TSAT of 12% is diagnostic for absolute iron deficiency in adults without inflammation (threshold <16%) and remains diagnostic even in inflammatory conditions (threshold <20%). 1
- Serum iron of 32 µg/dL is markedly low, confirming inadequate iron availability for red blood cell production. 1
- The combination of low serum iron with low TSAT indicates the bone marrow lacks sufficient available iron to synthesize hemoglobin, regardless of total body iron stores. 1
Critical next step: You must obtain a serum ferritin level to distinguish between absolute and functional iron deficiency, as this fundamentally changes your treatment approach. 1
Complete Your Diagnostic Work-Up Immediately
Essential Laboratory Tests (Order Within 1 Week)
Serum ferritin – This is the single most important missing value. 1
- If ferritin <30 ng/mL → absolute iron deficiency
- If ferritin 30-100 ng/mL → likely mixed picture
- If ferritin 100-300 ng/mL with TSAT <20% → functional iron deficiency 1
Complete blood count with hemoglobin, hematocrit, MCV, and reticulocyte count to assess anemia severity and red cell indices. 1
C-reactive protein to identify chronic inflammation that would alter ferritin interpretation and treatment choice. 1
Renal function (creatinine, eGFR) because chronic kidney disease profoundly influences iron metabolism and mandates different treatment thresholds. 1
Mandatory Evaluation for Blood Loss
In men and postmenopausal women: Gastrointestinal investigation with colonoscopy and upper endoscopy is mandatory to exclude occult malignancy as a source of chronic blood loss. 1
In premenopausal women: Assess menstrual blood loss patterns to identify gynecologic sources. 2
Additional considerations: Dietary insufficiency, malabsorption (celiac disease, inflammatory bowel disease), NSAID use, frequent blood donation, or high-impact athletic activity causing hemolysis. 1
Treatment Algorithm Based on Ferritin Results
Scenario 1: Ferritin <30 ng/mL (Absolute Iron Deficiency Without Inflammation)
Start oral iron supplementation:
- Elemental iron 100-200 mg daily in divided doses (e.g., ferrous sulfate 325 mg = 65 mg elemental iron, taken 2-3 times daily). 1
- Alternate-day dosing improves absorption and reduces gastrointestinal side effects compared with daily dosing. 1
- Common adverse effects include constipation, diarrhea, and nausea. 1
Target goals:
- Ferritin ≥30-45 ng/mL and TSAT ≥20%. 1
- Hemoglobin should increase by 1-2 g/dL within 4-8 weeks of treatment initiation. 1
Recheck iron studies at 8-10 weeks after starting oral iron. 1
Scenario 2: Ferritin 30-100 ng/mL with TSAT 12% (Mixed Picture)
This suggests a combination of true iron deficiency and possible early inflammation. 1
- Trial of oral iron is reasonable if CRP is normal.
- Switch to IV iron if CRP is elevated or if no hemoglobin response after 8-10 weeks of adequate oral therapy. 1
Scenario 3: Ferritin 100-300 ng/mL with TSAT 12% (Functional Iron Deficiency)
This is functional iron deficiency—iron is sequestered in storage sites by hepcidin and unavailable for erythropoiesis despite "normal" ferritin. 1
Oral iron is ineffective and should NOT be used because hepcidin blocks intestinal iron absorption in inflammatory states. 1
Intravenous iron is mandatory:
- Preferred formulations: Ferric carboxymaltose, iron sucrose, or low-molecular-weight iron dextran. 1
- Dosing example: Ferric carboxymaltose 1 g IV over 15 minutes as a single dose, or iron sucrose 100 mg IV at sequential dialysis sessions (if on hemodialysis). 1, 3
- IV iron bypasses hepcidin-mediated intestinal blockade and directly delivers iron to bone marrow. 1
Target goals:
- Ferritin ≥100 ng/mL and TSAT ≥20%. 1
Recheck iron studies 4-8 weeks after the last IV iron infusion—do NOT measure within 4 weeks because circulating iron interferes with assay accuracy. 1
Scenario 4: Ferritin >300 ng/mL with TSAT 12% (Severe Functional Deficiency)
This indicates severe inflammation with profound iron sequestration. 1
- IV iron is required as first-line therapy. 1
- Consider erythropoiesis-stimulating agents (ESAs) if no response to IV iron alone, particularly in chronic kidney disease or heart failure. 1
- Maintain TSAT >20% during ESA therapy to ensure sufficient iron availability for red cell production. 1
Common Diagnostic Pitfalls to Avoid
Do not rely on serum iron alone—it has high intra-individual variability, diurnal fluctuations, and post-prandial changes; normal serum iron does not exclude iron deficiency. 1
Do not interpret ferritin without TSAT—ferritin is an acute-phase reactant and can be falsely elevated in inflammation, masking true iron deficiency. 1
Do not measure iron parameters within 4 weeks of IV iron infusion—circulating iron yields falsely elevated results. 1
Do not use oral iron in functional iron deficiency with active inflammation—it is ineffective because hepcidin blocks intestinal absorption. 1
Do not assume elevated ferritin means iron overload in inflammatory states—it actually reflects inflammation-driven iron sequestration. 1
When to Consider IV Iron Regardless of Ferritin
Specific indications for intravenous iron include: 1
- Chronic kidney disease with eGFR <30 mL/min/1.73 m²
- Heart failure (NYHA class II-III) with ferritin <100 ng/mL or ferritin 100-300 ng/mL plus TSAT <20%
- Active inflammatory bowel disease
- Intolerance to oral iron (nausea, constipation)
- Lack of response after 4-8 weeks of adequate oral therapy
- Documented malabsorption
- Ongoing blood loss that exceeds oral replacement capacity
Monitoring Response to Treatment
If oral iron: Recheck hemoglobin at 4 weeks—expect 1-2 g/dL increase. If no response, consider malabsorption, continued bleeding, or switch to IV iron. 2
If IV iron: Recheck CBC and iron parameters (ferritin, TSAT) at 4-8 weeks after the last infusion. 1
If using ESAs: Maintain TSAT >20% throughout therapy to optimize dose-response. 1