How to manage patients with iron deficiency (ID) and low iron saturation but normal ferritin levels?

Management of Iron Deficiency with Low Iron/Saturation but Normal Ferritin

Patients with low iron and iron saturation but normal ferritin levels should be diagnosed with functional iron deficiency and treated with iron supplementation despite normal ferritin values. 1

Diagnostic Considerations

Understanding Iron Parameters in This Context

• Ferritin: While normally a reliable indicator of iron stores, ferritin is an acute-phase reactant that increases during inflammation, masking true iron deficiency 2
• Transferrin saturation (TSAT): A more reliable marker of iron availability in inflammatory states; TSAT <20% indicates iron deficiency regardless of ferritin levels 1
• Iron deficiency diagnosis thresholds:
  • In non-inflammatory states: Ferritin <30 μg/L indicates iron deficiency 1
  • In inflammatory conditions: Ferritin <100 μg/L OR ferritin 100-300 μg/L with TSAT <20% indicates iron deficiency 1, 2

Evaluation Algorithm

1. Measure both ferritin AND transferrin saturation simultaneously 1
2. If TSAT <20% despite normal ferritin, diagnose functional iron deficiency 1
3. Check inflammatory markers (CRP, ESR) to determine if inflammation is present 1
4. Consider reticulocyte hemoglobin content (CHr) if available; CHr <30 pg is predictive of response to IV iron 1, 3

Treatment Approach

First-Line Treatment

• Oral iron supplementation: Ferrous sulfate 325 mg daily or on alternate days 4, 5
  • Take on empty stomach for optimal absorption
  • Consider vitamin C (500 mg) with iron to enhance absorption
  • Avoid taking with tea, coffee, calcium supplements, or high-fiber foods

For Poor Response to Oral Iron or Inflammatory Conditions

• Intravenous iron should be considered when: 1, 4
  • Oral iron is poorly tolerated
  • Inflammatory condition is present (e.g., IBD, heart failure, CKD)
  • Rapid correction is needed
  • Iron malabsorption is suspected

Dosing for IV Iron

• Iron sucrose 200 mg twice weekly until calculated iron deficit is corrected 6
• For patients with chronic heart failure: Consider ferric carboxymaltose based on weight and hemoglobin levels 1

Special Considerations for Specific Conditions

Chronic Heart Failure

• Iron deficiency in heart failure is defined as ferritin <100 μg/L OR ferritin 100-300 μg/L with TSAT <20% 1
• IV iron has demonstrated improvements in exercise capacity, quality of life, and reduced hospitalizations 1

Chronic Kidney Disease

• Higher ferritin targets (>200 ng/mL) and TSAT >20% are recommended 1
• IV iron may be more effective than oral iron in CKD patients 1, 7
• For CKD patients with ferritin 500-1200 ng/mL but TSAT <25%, IV iron can still improve hemoglobin levels 3

Inflammatory Bowel Disease

• Iron deficiency is common (13-90% of patients) 5
• Inflammation increases hepcidin, restricting iron uptake despite normal ferritin 2
• IV iron may be preferable due to poor oral absorption and GI side effects 1

Monitoring and Follow-up

• Recheck iron studies (ferritin and TSAT) after 8-10 weeks of treatment 4
• For chronic conditions, monitor iron status 1-2 times per year 1
• Do not measure ferritin immediately after IV iron (falsely elevated) 4
• Consider underlying causes of iron deficiency (e.g., blood loss, malabsorption) 5

Common Pitfalls to Avoid

• Relying solely on ferritin: Normal ferritin does not exclude iron deficiency in inflammatory states 2
• Using MCV or MCH alone: These are unreliable markers of iron deficiency, especially with inflammation 1
• Measuring serum iron alone: Has large diurnal variations and is unreliable 1
• Overlooking functional iron deficiency: Patients with inflammatory conditions may have restricted iron availability despite normal ferritin 2
• Excessive iron supplementation: Avoid iron supplementation when ferritin >500 μg/L without low TSAT, as this may lead to iron overload 4