What is the recommended treatment for severe iron deficiency?

Treatment of Severe Iron Deficiency

For severe iron deficiency, start with oral ferrous sulfate 200 mg once daily (or on alternate days if not tolerated), and reserve intravenous iron for patients with hemoglobin <10 g/dL, intolerance to oral preparations, malabsorption, active inflammatory disease, or need for rapid correction. 1

First-Line Oral Iron Therapy

Oral iron remains the preferred initial treatment for most patients with severe iron deficiency. 1

• Ferrous sulfate 200 mg once daily is the gold standard, providing approximately 65 mg of elemental iron 1, 2
• Alternative ferrous salts (gluconate, fumarate) are equally effective 1
• If gastrointestinal side effects occur, switch to alternate-day dosing (e.g., 200 mg every other day), which maintains efficacy while significantly reducing nausea 1, 3
• Adding ascorbic acid (vitamin C) enhances absorption and should be considered when response is poor 1
• Liquid preparations may be tolerated when tablets are not 1

Expected Response and Monitoring

• Hemoglobin should rise by at least 10 g/L (1 g/dL) after 2 weeks of treatment 1
• Target hemoglobin increase of 2 g/dL after 3-4 weeks 1
• Continue treatment for 3 months after hemoglobin normalization to replenish iron stores 1

Indications for Intravenous Iron

Parenteral iron should be used when oral therapy is inadequate or inappropriate. The 2021 British Society of Gastroenterology guidelines provide the most current framework 1:

Absolute Indications for IV Iron:

• Severe anemia (hemoglobin <10 g/dL or 100 g/L) 1
• Intolerance to at least two different oral iron preparations 1
• Malabsorption conditions (celiac disease, post-bariatric surgery, inflammatory bowel disease) 1, 2
• Active inflammatory bowel disease 1
• Pronounced disease activity in chronic inflammatory conditions 1
• Non-compliance with oral therapy 1
• Need for rapid hemoglobin correction (pre-operative, symptomatic anemia with circulatory compromise) 1, 2
• Pregnancy (second and third trimesters) 2
• Chronic kidney disease or heart failure with functional iron deficiency 1, 2

IV Iron Advantages Over Older Guidelines:

The evidence has evolved significantly since 2000. Modern IV iron formulations are safer, better tolerated, and produce faster responses than the older guidelines suggested 1:

• Newer formulations (ferric carboxymaltose, ferric derisomaltose) allow high-dose infusions (500-1000 mg) in a single session 4
• IV iron is at least as effective as oral iron and delivers faster response rates 1
• Anaphylactic reactions are rare with modern preparations 1
• The rise in hemoglobin can be clinically meaningful within one week 1

Common Pitfall:

The 2000 guidelines 1 stated that "the rise in hemoglobin is no quicker than with oral preparations" for parenteral iron—this is outdated and contradicted by more recent evidence 1. Modern IV iron formulations produce faster clinical responses.

Dosing Regimens for IV Iron

Iron Sucrose (Venofer):

• Adults with non-dialysis chronic kidney disease: 200 mg IV over 15 minutes on 5 occasions over 14 days (total 1000 mg) 5
• Alternative: 500 mg diluted in 250 mL 0.9% NaCl over 3.5-4 hours on Day 1 and Day 14 5

Ferric Gluconate (Ferrlecit):

• 125 mg IV per dialysis session, typically requiring 8 sessions for repletion (total 1000 mg) 6
• Can be given undiluted as slow IV injection (up to 12.5 mg/min) or diluted in 100 mL 0.9% NaCl over 1 hour 6

Failure to Respond to Oral Iron

If hemoglobin fails to rise by at least 10 g/L after 2 weeks of daily oral iron, investigate the following causes 1:

• Poor compliance (most common) 1
• Continued blood loss 1
• Malabsorption 1
• Misdiagnosis 1
• Concurrent vitamin B12 or folate deficiency 1
• Bone marrow pathology 1
• Systemic inflammatory disease 1

Blood Transfusion

Transfusion should be reserved for severe symptomatic anemia with circulatory compromise 1:

• Target hemoglobin of 70-90 g/dL (80-100 g/dL in unstable coronary artery disease) 1
• Transfusion does not replenish iron stores—each unit of packed red cells contains only 200 mg elemental iron 1
• Iron replacement therapy must follow transfusion to address the underlying deficiency 1

Special Populations

Inflammatory Bowel Disease:

• IV iron is preferred over oral iron in active IBD due to concerns that unabsorbed oral iron may exacerbate inflammation through reactive oxygen species generation 1
• Patients with mild anemia (Hb >10 g/dL) and inactive disease may tolerate oral iron (100 mg/day) 1

Chronic Kidney Disease and Heart Failure:

• Functional iron deficiency is common (transferrin saturation <20% despite normal/elevated ferritin) 1
• IV iron is standard of care in these populations 1, 2
• May improve symptoms and quality of life independent of hemoglobin response 1

Pregnancy:

• IV iron is indicated in second and third trimesters when oral iron is ineffective or not tolerated 2