What is the recommended treatment for a patient with low iron saturation and normal indices otherwise?

Management of Low Iron Saturation with Otherwise Normal Indices

Start with oral iron supplementation at 50-100 mg elemental iron once daily or every other day, as this isolated finding of low transferrin saturation (<20%) represents functional iron deficiency that typically responds well to oral therapy. 1

Initial Assessment and Diagnosis

Low transferrin saturation (TSAT) with normal hemoglobin, MCV, and ferritin indicates functional iron deficiency rather than absolute iron deficiency. 1 This occurs when:

• Iron stores may be adequate (normal ferritin), but iron is not being effectively mobilized for erythropoiesis 1
• TSAT <20% indicates insufficient circulating iron available for red blood cell production 1
• Inflammation may be present, as it affects iron metabolism by upregulating hepcidin, which blocks iron release from stores 1

Key diagnostic step: Check C-reactive protein (CRP) to identify underlying inflammation, as ferritin can be falsely elevated in inflammatory states while true iron deficiency exists. 1, 2

First-Line Treatment: Oral Iron

Recommended approach:

• Ferrous sulfate 325 mg (65 mg elemental iron) once daily is the preferred initial therapy due to lowest cost and proven efficacy 1, 3
• Alternate-day dosing (every other day) may improve tolerability with similar or equal iron absorption compared to daily dosing 1
• Add vitamin C (250-500 mg) with iron to enhance absorption 1
• Take on empty stomach when possible, though with food if gastrointestinal side effects occur 1

Duration: Continue for approximately 3 months after hemoglobin normalizes to replenish iron stores 1

Monitoring Response

Reassess at 4 weeks:

• Check hemoglobin and TSAT to confirm response 1
• If TSAT improves and patient tolerates therapy, continue oral iron 1
• Do not recheck ferritin immediately after starting therapy, as it takes 8-10 weeks to accurately reflect iron repletion 1, 2

When to Escalate to Intravenous Iron

Consider IV iron if: 1

• No improvement in TSAT or hemoglobin after 4 weeks of adequate oral therapy
• Gastrointestinal intolerance to oral iron (constipation, nausea, diarrhea)
• Malabsorption conditions present (celiac disease, inflammatory bowel disease, post-bariatric surgery) 1
• Active inflammation with compromised absorption 1
• Ongoing blood loss exceeding intestinal absorption capacity 4

Preferred IV formulations: 1

• Ferric carboxymaltose (1000 mg over 15 minutes) - allows single-dose repletion 1
• Ferric derisomaltose (500-1000 mg per infusion) 5
• Iron sucrose (200 mg over 10 minutes) - requires multiple doses 1

Important safety consideration: True anaphylaxis with modern IV iron formulations is extremely rare (<1:250,000). Most reactions are complement activation-related pseudo-allergy (infusion reactions), not true allergic reactions. 1

Special Populations Requiring Different Approach

Chronic inflammatory conditions (inflammatory bowel disease, chronic kidney disease, heart failure):

• IV iron is preferred over oral due to hepcidin-mediated absorption blockade 1
• Target TSAT ≥20% and ferritin 100-500 ng/mL 1

Pregnancy (second/third trimester):

• IV iron is preferred for rapid repletion 3

Common Pitfalls to Avoid

• Do not supplement iron if ferritin is normal/high (>300-800 ng/mL) without documented low TSAT, as this is potentially harmful and indicates adequate stores 1, 2
• Do not use high-dose daily oral iron (>200 mg elemental iron daily), as this increases side effects without improving absorption 1
• Do not ignore underlying inflammation - treat the inflammatory condition to improve iron utilization 1
• Do not check ferritin too early after IV iron administration, as levels are falsely elevated for 8-10 weeks 1

Long-Term Management

After successful repletion:

• Monitor TSAT and hemoglobin every 3-6 months initially 1, 2
• Identify and address underlying cause of functional iron deficiency 3
• Consider intermittent oral supplementation if deficiency recurs 2