In a patient with normal hemoglobin and hematocrit, low serum iron, low transferrin saturation, and a ferritin level of 62 µg/L (within normal range), should iron supplementation be started?

Should Iron Supplementation Be Started?

No, iron supplementation should not be started in this patient with normal hemoglobin/hematocrit, ferritin of 62 µg/L, and low transferrin saturation, because the normal hemoglobin indicates no anemia is present and iron therapy is not justified without evidence of anemia or classic iron deficiency (ferritin <25 ng/mL in males or <11 ng/mL in females). 1

Clinical Context and Interpretation

Your patient presents with:

• Normal hemoglobin and hematocrit (no anemia)
• Low serum iron and low transferrin saturation (suggesting iron-deficient erythropoiesis)
• Ferritin 62 µg/L (within normal laboratory range)

This constellation creates diagnostic ambiguity, but guidelines provide clear direction based on the absence of anemia.

Why Iron Supplementation Is Not Indicated

Guideline-Based Reasoning

The Canadian Society of Nephrology explicitly states that for patients with hemoglobin <110 g/L and ferritin <100 ng/mL or TSAT <20%, treatment with iron is not justified in patients without evidence of classic iron deficiency (ferritin <25 ng/mL in males, <11 ng/mL in females). 1 Since your patient has normal hemoglobin (not <110 g/L), this recommendation applies even more strongly—there is no anemia to treat. 1

The ESPEN Micronutrient Guideline reinforces that iron supplementation in the presence of normal or high ferritin values is not recommended and is potentially harmful. 1 While 62 µg/L is not "high," it is well above the threshold for classic iron deficiency. 1

The Ferritin Threshold That Matters

• Classic (absolute) iron deficiency is defined as ferritin <25 ng/mL in males and <11 ng/mL in females in the absence of inflammation. 1, 2
• Your patient's ferritin of 62 µg/L is 2.5-fold higher than the male threshold and nearly 6-fold higher than the female threshold. 1, 2
• Ferritin <30 ng/mL (without inflammation) is the threshold used by most guidelines to confirm absolute iron deficiency requiring treatment. 2

Low TSAT Does Not Override Normal Hemoglobin

• TSAT <20% indicates iron-deficient erythropoiesis (functional iron deficiency), meaning the bone marrow lacks sufficient available iron for red blood cell production. 2
• However, functional iron deficiency is clinically relevant only when it causes anemia or when patients require erythropoiesis-stimulating agents (ESAs). 1
• In your patient, normal hemoglobin proves that erythropoiesis is adequate despite the low TSAT—the bone marrow is successfully producing red blood cells. 1

What This Patient Actually Needs

1. Rule Out Inflammation

Low TSAT with "normal-range" ferritin can indicate early inflammation masking true iron deficiency, because ferritin is an acute-phase reactant. 1, 2, 3

• Check C-reactive protein (CRP) to identify occult inflammation. 2
• If CRP is elevated:
  • Ferritin up to 100 ng/mL may still indicate true iron deficiency in inflammatory states. 1, 2
  • TSAT <20% with ferritin 30-100 ng/mL suggests combined true iron deficiency and anemia of chronic disease. 1, 2
  • Investigate underlying chronic conditions: chronic kidney disease (check eGFR), heart failure, inflammatory bowel disease, malignancy. 2

2. Identify Ongoing Blood Loss

In men and postmenopausal women, gastrointestinal evaluation is mandatory to exclude occult malignancy as a source of chronic blood loss. 2

• Low serum iron + low TSAT + normal hemoglobin may represent early compensated blood loss before anemia develops. 2, 4
• Endoscopic evaluation (colonoscopy if age >50) is recommended. 5
• In premenopausal women, assess menstrual blood loss patterns. 5

3. Monitor for Progression

If no inflammation or blood loss is found, repeat CBC and iron studies in 3-6 months to detect progression to anemia. 2

• A hemoglobin decrease of 1-2 g/dL would then justify iron supplementation. 5
• Hemoglobin and hematocrit alone are unreliable for detecting early iron depletion, which is why you ordered the full iron panel. 4

Common Pitfalls to Avoid

Pitfall 1: Treating Laboratory Values Instead of Clinical Disease

Iron supplementation is indicated to treat anemia or prevent anemia in high-risk patients (e.g., CKD, heart failure, pregnancy)—not to "normalize" TSAT in asymptomatic patients with normal hemoglobin. 1

Pitfall 2: Ignoring Inflammation

Ferritin 62 µg/L may be falsely elevated by inflammation, masking true iron deficiency. 1, 2, 3 Always check CRP before concluding iron stores are adequate. 2

Pitfall 3: Missing Occult Blood Loss

Low TSAT with normal hemoglobin may represent early compensated blood loss. 2, 5 Failure to investigate the GI tract can miss malignancy. 5

Pitfall 4: Relying on Serum Iron Alone

Serum iron has high intra-individual variability, diurnal fluctuations, and post-prandial changes—normal serum iron does not exclude iron deficiency. 2 TSAT and ferritin must be interpreted together. 2

When Iron Supplementation Would Be Indicated

Iron therapy would be justified if:

1. Hemoglobin drops below normal (anemia develops). 1, 5
2. Ferritin falls to <25-30 ng/mL (classic iron deficiency). 1, 2
3. Chronic inflammatory condition is diagnosed (CKD with eGFR <30, heart failure NYHA II-III, active IBD) and ferritin <100 ng/mL with TSAT <20%. 2
4. Patient requires ESAs for anemia of chronic disease—iron supplementation optimizes ESA response. 1

Monitoring Algorithm

Step 1: Check CRP to assess for inflammation. 2

Step 2: If CRP elevated:

• Investigate chronic disease (eGFR, echocardiogram, colonoscopy). 2
• If chronic disease confirmed and hemoglobin drops, consider IV iron (bypasses hepcidin blockade). 2

Step 3: If CRP normal:

• Evaluate for GI blood loss (endoscopy if age >50 or alarm symptoms). 2, 5
• Repeat CBC and iron panel in 3-6 months. 2

Step 4: Start iron supplementation only if:

• Hemoglobin falls below normal, or
• Ferritin drops to <25-30 ng/mL, or
• Chronic inflammatory disease is diagnosed with ferritin <100 ng/mL. 1, 2