How should iron deficiency anemia (IDA) be managed in a patient with low iron levels and transferrin saturation?

Laboratory Interpretation and Management Approach

Current Iron Status Assessment

This patient has functional iron deficiency without anemia. The hemoglobin is normal at 140 g/L, but serum iron (9.3 μmol/L) and transferrin saturation (15%) are both low, while ferritin (63 μg/L) remains in the normal range 1. The mildly elevated ESR (23 mm/hr) suggests underlying inflammation, which complicates interpretation of iron parameters 1.

Key Diagnostic Considerations

• Transferrin saturation <20% with ferritin 30-100 μg/L indicates functional iron deficiency, particularly in the presence of inflammation 1
• The ferritin of 63 μg/L falls in the "gray zone" (30-100 μg/L) where both true iron deficiency and anemia of chronic disease likely coexist 1
• Without inflammation, ferritin <30 μg/L or transferrin saturation <16% defines iron deficiency; with inflammation, the ferritin threshold increases to 100 μg/L 1
• The elevated ESR and borderline elevated eosinophils (0.40 x10⁹/L, upper limit 0.4) suggest an inflammatory or allergic process requiring investigation 1

Management Algorithm

Step 1: Identify and Treat Underlying Cause

Before initiating iron therapy, investigate the source of iron deficiency 2, 3:

• Gastrointestinal evaluation (gastroscopy and colonoscopy) is essential, as 9% of patients over 65 with iron deficiency have gastrointestinal cancer 4
• Screen for celiac disease with serological testing 3
• Assess for menstrual blood loss in premenopausal women 2
• Review medications, particularly NSAIDs and anticoagulants 2
• Evaluate for inflammatory bowel disease given the elevated ESR 1

Step 2: Iron Supplementation Strategy

Oral iron is first-line therapy for this patient 2, 5:

• Ferrous sulfate 325 mg daily or on alternate days (alternate-day dosing may improve absorption and reduce side effects) 1, 2
• Typical therapeutic doses range 100-200 mg elemental iron daily 1
• Take with meals to minimize gastrointestinal side effects (nausea, constipation, black stools) 6
• Avoid concurrent tetracycline antibiotics within 2 hours of iron administration 6

Step 3: Monitoring Response

Reassess hemoglobin and iron parameters after 8-10 weeks 1, 4:

• Expect hemoglobin increase of 1-2 g/dL (10-20 g/L) within one month if oral iron is effective 4
• Do not recheck ferritin earlier than 8-10 weeks after starting therapy, as levels may be falsely elevated 1
• Failure to respond suggests malabsorption, continued bleeding, or unidentified lesion 4

Step 4: Consider Intravenous Iron if Oral Therapy Fails

Intravenous iron is indicated for 2, 5:

• Oral iron intolerance or malabsorption (celiac disease, post-bariatric surgery) 2
• Chronic inflammatory conditions (IBD, CKD, heart failure) 1, 2
• Ongoing blood loss 2
• Lack of response to oral iron after appropriate trial 4, 5

Preferred IV formulations include ferric carboxymaltose or iron sucrose, which allow rapid administration of large single doses with minimal risk (<1:250,000 serious reactions) 1, 5.

Critical Pitfalls to Avoid

• Do not ignore the low transferrin saturation despite "normal" ferritin - this pattern indicates functional iron deficiency requiring treatment 1
• Do not supplement iron without investigating the underlying cause - missing gastrointestinal malignancy is a serious error 3, 4
• Do not recheck ferritin too early (before 8-10 weeks), as it will be falsely elevated and misleading 1
• Do not continue oral iron indefinitely without response - failure to increase hemoglobin by 1-2 g/dL within one month mandates further investigation 4
• Do not overlook the elevated ESR - this suggests an inflammatory process that may require specific treatment beyond iron supplementation 1

Special Considerations for Inflammation

In the presence of inflammation (elevated ESR), iron metabolism is altered 1:

• Inflammatory cytokines (TNF-α, IL-6) increase hepcidin production, which blocks intestinal iron absorption and sequesters iron in macrophages 1
• This may reduce oral iron efficacy and favor intravenous administration if inflammation persists 1
• Transferrin saturation <20% with ferritin >100 μg/L would indicate anemia of chronic disease; this patient's ferritin of 63 μg/L suggests combined deficiency 1