What is the appropriate management for a patient with severe iron deficiency anemia, characterized by hypochromic microcytic anemia with low hemoglobin, low ferritin, and low iron saturation?

Workup and Management of Severe Iron Deficiency Anemia

This patient requires immediate oral iron supplementation with ferrous sulfate 324 mg (65 mg elemental iron) one to three times daily, alongside urgent investigation for the source of iron loss, particularly gastrointestinal pathology including malignancy. 1, 2

Immediate Diagnostic Workup

Confirm Iron Deficiency

• The laboratory values (ferritin 6 μg/L, iron saturation 4%, hemoglobin 8.5 g/dL) definitively confirm severe iron deficiency anemia 1, 2
• Ferritin <15 μg/L indicates absent iron stores, and transferrin saturation <16% confirms absolute iron deficiency 1, 2, 3
• The severity warrants both treatment and investigation simultaneously 1

Mandatory Investigations

• Bidirectional endoscopy (gastroscopy and colonoscopy) is the standard first-line investigation for adults with unexplained iron deficiency anemia to exclude gastrointestinal malignancy 1
• Perform urinalysis or urine microscopy to exclude urinary blood loss 1
• Screen for celiac disease with serology (tissue transglutaminase antibodies), as it is found in 3-5% of iron deficiency anemia cases 1
• Assess for Helicobacter pylori infection, which can impair iron absorption 1
• In premenopausal women, evaluate menstrual blood loss patterns 1
• Check serum creatinine and glomerular filtration rate to assess for chronic kidney disease 1

Treatment Protocol

First-Line Oral Iron Therapy

• Initiate ferrous sulfate 324 mg (65 mg elemental iron) orally one to three times daily 1, 2, 3, 4
• Continue treatment for at least 3 months after hemoglobin normalizes to replenish iron stores 2, 3, 5
• Iron is absorbed better on an empty stomach; if not tolerated, take with meals containing meat protein 1
• Adding 500 mg vitamin C (ascorbic acid) enhances absorption, particularly when taken with food 1, 2, 3
• Alternative formulations (ferrous gluconate or ferrous fumarate) may be tried if gastrointestinal side effects (nausea, constipation, abdominal pain) are intolerable 1, 2, 3

Expected Response and Monitoring

• A good response is defined as hemoglobin rise ≥10 g/L (≥1 g/dL) within 2 weeks, which confirms iron deficiency 1, 2, 3
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks of starting treatment 2, 3
• Monitor hemoglobin and iron studies at 2 weeks, 4 weeks, 3 months, and every 3 months for the first year 2, 3

When to Consider Intravenous Iron

• If hemoglobin fails to rise ≥1 g/dL within 2 weeks, consider non-compliance, ongoing blood loss, malabsorption, or need for intravenous iron 1, 2, 3
• Intravenous iron is indicated when oral iron is not tolerated, malabsorption is present, or rapid repletion is needed 1, 6
• In inflammatory conditions or when hepcidin is elevated, oral iron absorption is impaired and intravenous iron may be more effective 1
• Available formulations include iron sucrose, ferric gluconate, ferric carboxymaltose, and low molecular weight iron dextran 1
• Calculate total iron deficit based on hemoglobin deficit and need to rebuild stores; monitor ferritin and keep <500 μg/L to avoid toxicity 1

Critical Pitfalls to Avoid

Investigation Errors

• Never assume all microcytic anemia is iron deficiency—differentiate from anemia of chronic disease, thalassemia, and sideroblastic anemia before treating 3
• Do not delay gastrointestinal investigation while treating; malignancy must be excluded urgently 1
• If MCV is disproportionately low relative to anemia severity or iron studies are normal, order hemoglobin electrophoresis to exclude thalassemia 3

Treatment Errors

• Do not stop iron supplementation when hemoglobin normalizes—continue for 3 months to replenish stores 2, 3, 5
• Recognize that proton pump inhibitors and H2-blockers impair iron absorption 1
• Recent evidence suggests alternate-day oral iron dosing may improve absorption and reduce side effects compared to daily dosing, as daily iron increases hepcidin levels 1

Special Considerations

• In patients with chronic inflammatory conditions (CKD, heart failure, inflammatory bowel disease), ferritin up to 100 μg/L may still indicate iron deficiency 1, 3
• If severe anemia persists despite adequate iron replacement, consider rare genetic disorders such as IRIDA (TMPRSS6 mutations), which causes resistance to oral iron and requires intravenous therapy 1, 2, 3
• Overlooking combined deficiencies (B12, folate) can delay recovery—assess if response is suboptimal 3