When is iron used to treat anemia?

Iron Therapy in Anemia: Indications and Approaches

Iron therapy is indicated for the treatment of iron deficiency anemia, which is the most common nutritional deficiency worldwide, affecting 1-4% of men and 4-17% of women in the United States. 1

Diagnostic Criteria for Iron Deficiency

• Ferritin is the most commonly used marker for diagnosing iron deficiency, with a recommended cut-off value of 45 μg/dL in individuals with anemia 1
• In patients with inflammatory conditions, iron deficiency may exist with ferritin levels between 45-100 μg/dL, requiring confirmatory testing with transferrin saturation, soluble transferrin receptor, or reticulocyte hemoglobin equivalent 1
• For healthy adults >15 years, a ferritin cut-off of 30 μg/L is appropriate; for children 6-12 years and adolescents 12-15 years, cut-offs of 15 and 20 μg/L are recommended 2

Indications for Iron Therapy

Iron Deficiency Anemia (IDA)

• Iron supplementation is recommended in all patients when iron deficiency anemia is present 1
• The goal of iron therapy is to normalize hemoglobin levels and replenish iron stores 1
• An increase in hemoglobin of at least 2g/dL within 4 weeks of treatment is considered an acceptable response 1

Specific Clinical Scenarios

1. Inflammatory Bowel Disease (IBD)

   • Iron therapy is indicated for all IBD patients with iron deficiency anemia 1
   • Intravenous iron should be given in individuals with IBD, iron deficiency anemia, and active inflammation with compromised absorption 1

2. Portal Hypertensive Gastropathy

   • Oral iron supplements should initially be used to replenish iron stores 1
   • Intravenous iron therapy should be used in patients with ongoing bleeding who do not respond to oral iron therapy 1

3. Gastric Antral Vascular Ectasia (GAVE)

   • Iron replacement should be provided alongside endoscopic therapy 1

4. Celiac Disease

   • Adherence to a gluten-free diet is essential to improve iron absorption 1
   • Consider oral iron supplementation based on severity of iron deficiency, followed by intravenous iron if stores don't improve 1

5. Small-Bowel Angioectasias

   • Endoscopic treatment should be accompanied with iron replacement 1

6. Bariatric Surgery

   • Intravenous iron therapy should be used in individuals who have undergone bariatric procedures that disrupt normal duodenal iron absorption 1

7. Pregnancy

   • Start oral, low-dose (30 mg/day) iron supplements at the first prenatal visit 1
   • For anemia during pregnancy, prescribe 60-120 mg/day of iron 1

Administration Routes and Considerations

Oral Iron Therapy

• Oral iron is typically the first-line treatment for iron deficiency anemia 1
• Common formulations include ferrous sulfate, ferrous fumarate, and ferrous gluconate 1
• Recommended dosing:
  • Adults: 28-50 mg elemental iron daily 2
  • Children and adolescents: dosage based on weight and severity of deficiency 1
• Side effects include constipation (12%), diarrhea (8%), and nausea (11%) 1
• Taking iron once daily is sufficient as more frequent dosing increases side effects without improving absorption 1
• Oral iron is better absorbed when taken on an empty stomach; vitamin C (500 mg) can enhance absorption 1

Intravenous (IV) Iron Therapy

Intravenous iron should be used in the following situations:

• Patient does not tolerate oral iron 1
• Ferritin levels do not improve with a trial of oral iron 1
• Patient has a condition where oral iron is not likely to be absorbed 1
• Hemoglobin is below 10 g/dL 1
• Patient has clinically active IBD 1
• Patient needs erythropoiesis-stimulating agents 1

IV iron formulations that can replace iron deficits with 1-2 infusions are preferred over those requiring more infusions 1

Monitoring and Follow-up

• To measure treatment success, repeat basic blood tests after 8-10 weeks 2
• After successful treatment of iron deficiency anemia with IV iron, re-treatment should be initiated when serum ferritin drops below 100 μg/L or hemoglobin below 12-13 g/dL (gender-dependent) 1
• Patients with repeatedly low ferritin will benefit from intermittent oral substitution and long-term follow-up every 6-12 months 2

Important Considerations and Pitfalls

• Long-term daily oral or IV iron supplementation in the presence of normal or high ferritin values is not recommended and potentially harmful 2
• All IV iron formulations have similar risks; true anaphylaxis is very rare, with most reactions being complement activation-related pseudo-allergy (infusion reactions) 1
• In patients with unexplained iron deficiency anemia, especially men and postmenopausal women, gastrointestinal evaluation is necessary to rule out malignancy 3, 4
• Red blood cell transfusions should be used rarely for hemodynamically stable patients with iron deficiency, irrespective of hemoglobin levels 5