How should low ferritin be evaluated and managed?

Evaluation and Management of Low Ferritin

Low ferritin requires immediate oral iron supplementation while simultaneously investigating the underlying cause through non-invasive testing for celiac disease and H. pylori, with bidirectional endoscopy reserved for men, postmenopausal women, or patients with alarm symptoms. 1

Diagnostic Thresholds and Interpretation

Ferritin cutoffs vary by clinical context:

• Ferritin <15 μg/L has 99% specificity for absolute iron deficiency and confirms the diagnosis definitively 2, 3
• Ferritin 15-30 μg/L indicates depleted iron stores requiring treatment 2
• Ferritin <45 μg/L provides optimal sensitivity-specificity balance (92% specificity) for clinical decision-making 1, 2

Critical caveat: Ferritin is an acute-phase reactant that rises during inflammation, infection, or tissue damage, potentially masking true iron deficiency 1, 2. In chronic inflammatory conditions (inflammatory bowel disease, chronic kidney disease, heart failure), the diagnostic threshold shifts upward to ferritin <100 μg/L 2, 4.

Always calculate transferrin saturation (TSAT): Values <16-20% confirm iron deficiency even when ferritin is elevated by inflammation 2, 3. The formula is: (serum iron × 100) ÷ total iron-binding capacity 2.

Immediate Management Algorithm

Step 1: Initiate Iron Supplementation Without Delay

Start oral iron immediately—do not wait for diagnostic workup completion 1:

• Ferrous sulfate 325 mg daily (65 mg elemental iron) OR 60-65 mg every other day 2, 5
• Alternate-day dosing improves absorption by 30-50% and reduces gastrointestinal side effects 2, 3
• Take on empty stomach for optimal absorption, or with meals if gastrointestinal symptoms occur 2
• Expected response: hemoglobin should rise ≥10 g/L within 2 weeks 2

Step 2: Screen for Common Underlying Causes

Perform non-invasive testing for all patients 1:

• Tissue transglutaminase IgA antibodies for celiac disease—present in 3-5% of iron deficiency cases and a frequent cause of treatment failure 2, 5
• Stool antigen or urea breath test for H. pylori infection 1, 2

Step 3: Determine Need for Endoscopic Evaluation

Bidirectional endoscopy (upper and lower) is strongly recommended for 1:

• All men with iron deficiency anemia (strong recommendation, moderate quality evidence)
• All postmenopausal women with iron deficiency anemia (strong recommendation, moderate quality evidence)
• Any patient ≥50 years regardless of sex 2
• Gastrointestinal symptoms (abdominal pain, altered bowel habits, visible blood) 1, 2
• Positive celiac or H. pylori testing requiring confirmation 1
• Failure to respond to adequate oral iron after 8-10 weeks 1, 2
• Strong family history of colorectal cancer 2

For premenopausal women (conditional recommendation, moderate quality evidence) 1:

• Younger premenopausal women with heavy menstrual bleeding and no gastrointestinal symptoms may reasonably select initial empiric iron supplementation alone 1
• Reserve endoscopy for those meeting the criteria above 1

When to Switch to Intravenous Iron

Intravenous ferric carboxymaltose (15 mg/kg, maximum 1000 mg per dose) is indicated for 2, 5:

• Oral iron intolerance (marked nausea, constipation, diarrhea)
• Confirmed malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery)
• Ongoing blood loss exceeding oral replacement capacity
• Chronic inflammatory conditions (chronic kidney disease, heart failure, cancer)
• Pregnancy in second/third trimester
• Lack of hemoglobin response after 8-10 weeks of adequate oral therapy

IV iron produces reticulocytosis within 3-5 days and yields a mean hemoglobin increase of ≈8 g/L over 8 days, demonstrating superior efficacy in these populations 2.

Follow-Up and Monitoring

Repeat complete blood count and ferritin at 8-10 weeks to assess response 1, 2:

• Target ferritin >100 ng/mL to restore iron stores and prevent recurrence 1, 2
• Continue iron supplementation for 3 months after hemoglobin normalizes to fully replenish ferritin 2
• If no improvement, consider malabsorption, non-compliance, ongoing blood loss, or need for IV iron 2

For high-risk populations (menstruating females, vegetarians, athletes, regular blood donors), screen ferritin every 6-12 months 2.

Critical Pitfalls to Avoid

Do not assume normal ferritin excludes iron deficiency in inflammatory states—transferrin saturation <20% confirms deficiency even with ferritin 30-100 μg/L 2, 4, 6.

Do not overlook celiac disease screening—its 3-5% prevalence in iron deficiency cases leads to treatment failure when missed 2, 5.

Do not delay endoscopic evaluation in high-risk patients (age ≥50, alarm symptoms, treatment failure)—gastrointestinal malignancy can present solely with iron deficiency 1, 2.

Do not discontinue iron therapy once hemoglobin normalizes—an additional 3 months of supplementation is required for ferritin to reach >100 ng/mL 2.

Do not continue daily iron supplementation indefinitely once ferritin normalizes—this is potentially harmful 2.