Treatment of Iron Deficiency Anemia with Concurrent Folate Deficiency
Start oral iron supplementation immediately with ferrous sulfate 200 mg once daily (not three times daily) and add folic acid 5 mg daily for a minimum of 4 months, but critically—you must first exclude vitamin B12 deficiency before initiating folate therapy to prevent precipitating subacute combined degeneration of the spinal cord. 1
Immediate Action Required
Check vitamin B12 level urgently before starting any folate supplementation. 1 The lab values show severe iron deficiency (transferrin saturation 7.5%, TIBC elevated at 2352) and low folate (3.2), but folate supplementation can mask B12 deficiency and cause irreversible neurological damage if B12 is also depleted. 1
Iron Replacement Strategy
Oral Iron Dosing (First-Line)
Prescribe ferrous sulfate 200 mg once daily, not three times daily. 1, 2 Hepcidin rises within hours of iron ingestion and blocks absorption for 48 hours, making multiple daily doses ineffective and causing more gastrointestinal side effects. 2
Add 500 mg vitamin C (ascorbic acid) with each iron dose to enhance absorption. 1, 2 This is particularly important when response is suboptimal.
Continue iron for 3 months after hemoglobin normalizes to replenish body stores. 1
Expected Response
- Hemoglobin should rise by 2 g/dL after 3-4 weeks. 1 Failure indicates poor compliance, continued blood loss, malabsorption, or misdiagnosis. 1
When to Use IV Iron Instead
Switch to intravenous iron if the patient fails two different oral iron formulations or has intolerance. 1, 2 IV iron delivers faster response rates and is safer than previously thought, though oral iron remains first-line for uncomplicated cases. 1
Parenteral iron is painful (intramuscular), expensive, carries anaphylaxis risk, and provides no faster hemoglobin rise than oral preparations. 1
Folate Replacement (After Excluding B12 Deficiency)
Prescribe folic acid 5 mg orally daily for a minimum of 4 months. 1, 3 This dose is standard for treating documented folate deficiency and is FDA-approved for megaloblastic anemias due to folate deficiency. 3
Critical Sequencing
Never initiate folic acid before confirming normal B12 levels. 1 If B12 deficiency coexists, treat B12 first with hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, then maintenance every 2-3 months lifelong. 1
If neurological symptoms exist (sensory/motor/gait abnormalities), give hydroxocobalamin 1 mg IM on alternate days until no further improvement, then every 2 months, and seek urgent neurology/hematology consultation. 1
Monitoring Protocol
Check hemoglobin and MCV every 3 months for the first year, then annually. 1, 2 This detects recurrence early, which occurs in >50% of patients within one year and often indicates ongoing pathology. 1
Recheck folate level after 4 months of supplementation to confirm correction. 1
Restart iron if hemoglobin or MCV falls below normal; check ferritin in doubtful cases. 1, 2
Investigation of Underlying Cause
This 19-year-old female requires investigation despite her age if she is not menstruating or if menstrual history doesn't explain the severity. 1 The British Society of Gastroenterology recommends investigating patients under 45 only if they have upper GI symptoms or non-menstrual causes, but the American Gastroenterological Association emphasizes that approximately one-third of patients have pathological abnormalities including GI malignancies. 2
Consider upper endoscopy with small bowel biopsy to exclude celiac disease, which commonly causes both iron and folate deficiency. 1 Antiendomysial antibody testing (with IgA level) is an alternative screening approach in young patients without alarm symptoms. 1
Evaluate for menorrhagia if menstruating—pictorial blood loss assessment charts have 80% sensitivity/specificity. 1
Common Pitfalls to Avoid
Do not prescribe iron three times daily—once daily dosing is equally effective with fewer side effects due to hepcidin regulation. 2
Do not give folic acid before excluding B12 deficiency—this can precipitate irreversible spinal cord damage. 1
Do not assume menstruation explains everything—even obvious sources may coexist with occult pathology requiring investigation. 2
Do not use intramuscular iron—there is no evidence it is less toxic or more effective than oral or IV iron. 1