Management of High Serum Folate with Low Ferritin and Iron Deficiency
The primary management is iron supplementation to correct the iron deficiency, while the elevated folate requires no treatment and should not distract from addressing the iron deficiency. The high folate is likely incidental (from supplementation or fortified foods) and does not cause harm or require intervention 1.
Immediate Diagnostic Confirmation
Confirm absolute iron deficiency by verifying ferritin <30 μg/L (or <45 μg/L with optimal sensitivity/specificity) and low serum iron with transferrin saturation <20% 2, 3.
Rule out inflammation that could falsely elevate ferritin by checking C-reactive protein, as ferritin >100-150 μg/L essentially excludes absolute iron deficiency even with inflammation 2, 4.
Assess for anemia using WHO criteria: hemoglobin <120 g/L in females or <130 g/L in males 1.
Check MCV and RDW to characterize the anemia pattern - iron deficiency typically shows low MCV with elevated RDW (>14%), distinguishing it from thalassemia 2.
Investigate the Underlying Cause
All adults with confirmed iron deficiency require investigation for the source of iron loss unless there is obvious non-GI blood loss 2, 5.
Gastrointestinal evaluation is mandatory in men and postmenopausal women with iron deficiency anemia, as GI pathology (including malignancy) is the most common cause 2, 5.
Upper endoscopy should be performed first, revealing a cause in 30-50% of patients, with small bowel biopsies obtained to screen for celiac disease (present in 2-3% of iron deficiency anemia patients) 2.
Colonoscopy should follow, particularly prioritized in elderly patients where colonic pathology is more likely 2.
In premenopausal women, heavy menstrual bleeding is the most common cause, but GI investigation is still warranted if oral iron therapy fails or if there are alarm symptoms 3, 5.
Iron Replacement Strategy
First-Line: Oral Iron Therapy
Initiate ferrous sulfate 325 mg daily or on alternate days as first-line therapy for most patients 2, 3.
Continue for at least 3 months after anemia correction to replenish iron stores 2, 4.
Alternative formulations (ferrous gluconate, ferrous fumarate) can be used if ferrous sulfate is not tolerated 2.
Adding ascorbic acid enhances absorption, and patients should be counseled on dietary enhancers while avoiding inhibitors of iron uptake 2, 4.
Use preparations with 28-50 mg elemental iron to prevent reduced compliance from gastrointestinal side effects 4.
Indications for Intravenous Iron
Intravenous iron is indicated when oral iron is inappropriate or ineffective 3, 6:
Oral iron intolerance with significant gastrointestinal side effects 3.
Impaired absorption (celiac disease, atrophic gastritis, post-bariatric surgery, inflammatory bowel disease) 3, 6.
Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer) where hepcidin upregulation blocks oral iron absorption 1, 3.
Second and third trimesters of pregnancy when rapid correction is needed 3.
Calculate total intravenous iron dose based on formulas for body iron deficit, allowing for hemoglobin correction and store rebuilding, with doses repeated every 3-7 days 1.
Monitor ferritin levels and preferably keep below 500 μg/L to avoid toxicity from iron overload, especially in children and adolescents 1.
Monitoring Protocol
Recheck hemoglobin and red cell indices at 8-10 weeks after initiating therapy to assess response 4.
Follow at 3-monthly intervals for one year, then annually to ensure sustained correction 2.
Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up 2.
For patients with repeatedly low ferritin, intermittent oral supplementation preserves iron stores, with monitoring every 6-12 months 4.
Critical Pitfalls to Avoid
Do not attribute the elevated folate as causative - high serum folate does not cause iron deficiency and requires no treatment 1. The folate elevation is incidental and should not delay iron replacement.
Do not assume dietary deficiency explains the anemia without full investigation - GI evaluation is still required even with poor dietary intake 2.
Do not overlook combined deficiencies - check vitamin B12 if MCV is not as low as expected or if neurological symptoms are present, as combined deficiencies can mask each other 2, 7.
Do not continue long-term daily iron supplementation once ferritin normalizes - this is potentially harmful and not recommended 4.
Do not miss inadequate response to oral iron - this may indicate malabsorption, non-compliance, or concomitant folate/B12 deficiency requiring parenteral iron or additional supplementation 7.