What is the management approach for a patient with normal hemoglobin (Hb) levels and low total iron, indicating iron deficiency without anemia?

Management of Iron Deficiency Without Anemia

Iron supplementation should be considered in patients with normal hemoglobin but low total iron, with treatment decisions based on symptoms and risk factors, as iron deficiency without anemia can impact quality of life and may progress to anemia if left untreated. 1, 2

Diagnosis Confirmation

• Iron deficiency without anemia (non-anemic iron deficiency or NAID) is characterized by normal hemoglobin levels but depleted iron stores, typically indicated by low serum ferritin 1
• Diagnostic criteria for iron deficiency include:
  • Serum ferritin <30 μg/L in adults (most specific marker in absence of inflammation) 1, 2
  • Transferrin saturation <20% 1
• In the presence of inflammation, ferritin may appear falsely normal; a cut-off of 45 μg/L provides good specificity (0.92) for iron deficiency 1

Treatment Decision Algorithm

Step 1: Evaluate for symptoms and risk factors

• Assess for symptoms that may be present even without anemia:
  • Fatigue, reduced physical performance, cognitive dysfunction 2, 3
  • Restless legs syndrome (affects 32-40% of iron-deficient patients) 3
  • Pica (affects 40-50% of iron-deficient patients) 3
• Identify risk factors:
  • Menstruating women, pregnancy, adolescence 2
  • Gastrointestinal conditions affecting absorption 3
  • Chronic inflammatory conditions (IBD, heart failure) 1, 3
  • Vegetarian/vegan diet, underweight, eating disorders 2

Step 2: Treatment approach based on patient profile

For symptomatic patients with iron deficiency without anemia:

• Oral iron supplementation is first-line therapy 1, 3
  • Ferrous sulfate 200 mg three times daily (or equivalent ferrous gluconate/fumarate) 1
  • Lower doses (28-50 mg elemental iron) may improve compliance by reducing gastrointestinal side effects 2
  • Consider alternate-day dosing to improve absorption and reduce side effects 3
  • Add ascorbic acid to enhance iron absorption if response is poor 1

For asymptomatic patients:

• The decision to treat is more controversial and depends on individual risk factors 1
• Treatment is warranted in high-risk populations (heart failure patients, pregnant women) 1, 3
• In heart failure patients with ferritin <100 ng/ml, iron therapy is recommended to target ferritin of 100 ng/ml 1

Step 3: Monitoring and follow-up

• Repeat basic blood tests (including ferritin) after 8-10 weeks to assess treatment response 2
• For patients with recurrent iron deficiency, consider intermittent oral supplementation and long-term follow-up every 6-12 months 2
• In heart failure patients, monitor ferritin levels and re-treat when ferritin drops below 100 μg/L 1

Special Considerations

• Intravenous iron should be considered in cases of:

  • Intolerance to at least two oral preparations 1
  • Poor absorption (celiac disease, post-bariatric surgery) 3
  • Chronic inflammatory conditions (IBD, CKD, heart failure) 3
  • Ongoing blood loss exceeding intestinal absorption capacity 4

• Investigate underlying causes of iron deficiency:

  • GI investigation is generally not warranted in premenopausal women without other risk factors 1
  • The threshold for investigation should be low in men, postmenopausal women, and those with GI symptoms 1
  • Screen for celiac disease, which is found in 3-5% of iron deficiency cases 1

Common Pitfalls to Avoid

• Avoid long-term daily iron supplementation in patients with normal or high ferritin, as this is potentially harmful 2
• Don't rely solely on ferritin in patients with inflammatory conditions; use transferrin saturation as an additional marker 1
• Don't overlook the need to identify and treat the underlying cause of iron deficiency 1
• Avoid excessive iron dosing, which can lead to poor compliance due to gastrointestinal side effects 2