What is the recommended assessment and treatment approach for a patient diagnosed with iron deficiency anemia?

Assessment and Treatment of Iron Deficiency Anemia

Diagnostic Criteria

Diagnose iron deficiency anemia using ferritin <45 ng/mL as the diagnostic threshold, which provides superior sensitivity and specificity compared to lower cutoffs. 1

• In patients without inflammation, ferritin <30 ng/mL confirms iron deficiency 2
• Transferrin saturation <20% supports the diagnosis, particularly when ferritin is equivocal 2
• Additional testing may be needed in patients with chronic kidney disease or underlying inflammatory conditions where ferritin can be falsely elevated 1

First-Line Treatment: Oral Iron

Start ferrous sulfate 200 mg (65 mg elemental iron) once daily, which is the preferred first-line treatment due to superior cost-effectiveness and equal efficacy to all other oral formulations. 3

Dosing Strategy

• Once-daily dosing is superior to multiple daily doses because hepcidin remains elevated for 48 hours after iron intake, blocking further absorption while increasing gastrointestinal side effects 3
• Alternative formulations (ferrous gluconate 325 mg or ferrous fumarate 325 mg) are equally effective if ferrous sulfate is not tolerated, though more expensive 3
• Take on an empty stomach for optimal absorption, but with food if gastrointestinal side effects occur 3

Enhancing Absorption

• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly critical when iron saturation is severely low 3
• Consider alternate-day dosing if daily dosing is not tolerated, as this increases fractional iron absorption with similar overall efficacy 3

Expected Response and Duration

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment 3
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores 3
• Check hemoglobin at 4 weeks; failure to rise by 2 g/dL indicates poor compliance, continued blood loss, or malabsorption 3

When to Switch to Intravenous Iron

Use intravenous iron when oral iron fails or is contraindicated, specifically for:

Absolute Indications

• Intolerance to at least two different oral iron preparations 3
• Inflammatory bowel disease with active inflammation and hemoglobin <10 g/dL 3
• Post-bariatric surgery patients due to disrupted duodenal absorption 3
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 3
• Celiac disease with inadequate response to oral iron despite gluten-free diet adherence 3

IV Iron Formulation Selection

• Prefer IV iron formulations that replace iron deficits in 1-2 infusions rather than multiple infusions 3
• Iron sucrose (Venofer) can be administered as 200 mg undiluted over 2-5 minutes or diluted in 100 mL normal saline over 15 minutes 4
• Ferric gluconate (Ferrlecit) is FDA-approved for iron deficiency anemia in chronic kidney disease patients on hemodialysis receiving erythropoietin 5
• Iron dextran allows total dose infusion in a single session but carries slightly higher anaphylaxis risk (0.6-0.7%) requiring resuscitation facilities available 3

Diagnostic Workup for Underlying Cause

Men and Postmenopausal Women

Perform bidirectional endoscopy (upper endoscopy and colonoscopy) to evaluate for gastrointestinal malignancy and other sources of blood loss. 1

• This is a strong recommendation based on moderate-quality evidence 1
• Test for Helicobacter pylori with non-invasive testing, followed by treatment if positive 1
• Screen for celiac disease with antiendomysial antibody (IgA type) and total IgA measurement first 1
• Perform small bowel biopsy only if celiac serology is positive 1

Premenopausal Women

• Assess menstrual blood loss first, as menorrhagia accounts for iron deficiency in 5-10% of menstruating women 3
• Consider pictorial blood loss assessment charts (80% sensitivity and specificity for menorrhagia) 3
• Bidirectional endoscopy is conditionally recommended even in premenopausal women, though those who place high value on avoiding endoscopy risks may reasonably choose initial iron replacement alone 1
• Proceed with endoscopy if there are alarm symptoms (weight loss, abdominal pain), family history of colon cancer, or failure to respond to iron therapy 3

After Negative Bidirectional Endoscopy

• Initial iron supplementation is preferred over routine video capsule endoscopy in uncomplicated patients 1
• Consider capsule endoscopy or CT/MRI enterography only if red flags present (involuntary weight loss, abdominal pain, elevated CRP) or if anemia persists despite adequate iron replacement 3

Special Population Considerations

Pregnant Women

• Start oral low-dose iron 30 mg/day at first prenatal visit for prevention 3
• Treat anemia with 60-120 mg/day elemental iron 3
• Refer for further evaluation if hemoglobin <9.0 g/dL 3
• Use IV iron during second and third trimesters if oral iron is inadequate 3, 2

Inflammatory Bowel Disease

• IV iron is first-line treatment when hemoglobin <10 g/dL with active inflammation 3
• Treat active inflammation first to enhance iron absorption and reduce iron depletion 3
• IV iron is more effective than oral iron in IBD patients (odds ratio 1.57 for achieving 2.0 g/dL hemoglobin increase) 3

Chronic Kidney Disease and Heart Failure

• IV iron is preferred in patients with CKD (24-85% have iron deficiency) and heart failure (37-61% have iron deficiency) due to chronic inflammation affecting oral iron absorption 2

Monitoring Protocol

• Recheck hemoglobin at 4 weeks to assess response 3
• Monitor hemoglobin and red cell indices every 3 months for the first year after correction, then again after another year 3
• If anemia does not resolve within 6 months despite appropriate therapy, reassess for ongoing blood loss, evaluate for malabsorption syndromes, and verify patient adherence 3

Critical Pitfalls to Avoid

• Never prescribe multiple daily doses of oral iron—this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade 3
• Never stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores 3
• Do not continue oral iron indefinitely without response—reassess after 4 weeks and switch to IV iron if hemoglobin fails to rise 3
• Do not overlook vitamin C supplementation when oral iron response is suboptimal 3
• Do not fail to identify and treat the underlying cause while supplementing iron 3
• Do not delay treatment while awaiting diagnostic workup unless colonoscopy is scheduled within days 3