What is the recommended treatment for low ferritin (iron‑deficiency anemia)?

Treatment of Low Ferritin (Iron Deficiency)

Start oral iron supplementation immediately with ferrous sulfate 65 mg elemental iron daily (or 60-65 mg every other day), and simultaneously screen for celiac disease and Helicobacter pylori infection, as these account for a significant proportion of treatment failures. 1, 2

Immediate Oral Iron Therapy

• Initiate ferrous sulfate providing 65 mg elemental iron daily without waiting for diagnostic workup completion. 2
• Alternate-day dosing (60-65 mg every other day) improves iron absorption by 30-50% and reduces gastrointestinal side effects compared to daily dosing. 3, 2
• Take on an empty stomach for optimal absorption; if gastrointestinal symptoms develop (constipation, nausea, diarrhea), take with meals or switch to alternate-day dosing. 2
• Expected response: hemoglobin should rise by ≥10 g/L within 2 weeks of starting therapy. 1, 2

Mandatory Screening for Underlying Causes

All Patients Require:

• Screen for celiac disease with tissue transglutaminase IgA antibodies—celiac disease accounts for 3-5% of iron-deficiency cases and is a frequent cause of treatment failure. 1, 2
• Test for Helicobacter pylori infection using stool antigen or urea-breath test, as the organism impairs iron absorption. 1, 2

Gastrointestinal Investigation Algorithm:

For adult men and postmenopausal women: Bidirectional endoscopy (upper GI endoscopy + colonoscopy) is mandatory because iron deficiency may be the sole manifestation of gastrointestinal malignancy. 1, 2

For premenopausal women: GI investigation is conditional rather than mandatory. Reserve bidirectional endoscopy for: 1, 2

• Age ≥50 years (higher malignancy risk)
• Gastrointestinal symptoms (abdominal pain, altered bowel habits, visible blood)
• Positive celiac or H. pylori testing requiring confirmation
• Lack of response to adequate oral iron after 8-10 weeks
• Strong family history of colorectal cancer

For young premenopausal women with heavy menstrual bleeding and no GI symptoms: Empiric oral iron supplementation without immediate endoscopy is appropriate. 2

Diagnostic Thresholds for Interpretation

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

Critical Caveat—Inflammation Raises Thresholds:

• In chronic inflammatory conditions (inflammatory bowel disease, chronic kidney disease, heart failure, cancer), use ferritin <100 ng/mL as the threshold for iron deficiency. 2
• Calculate transferrin saturation (TSAT): values <16-20% confirm iron deficiency even when ferritin is elevated by inflammation. 1, 2
• Ferritin is an acute-phase reactant that rises during inflammation, infection, or tissue damage, potentially masking true iron deficiency. 1, 2

Indications for Intravenous Iron Therapy

Switch to intravenous ferric carboxymaltose (15 mg/kg body weight, maximum 1,000 mg per dose) when any of the following are present: 4, 2

• Oral iron intolerance (marked nausea, constipation, diarrhea preventing adherence)
• 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, inflammatory bowel disease, cancer)
• Pregnancy in the second or third trimester
• Lack of hemoglobin response after 8-10 weeks of adequate oral iron therapy

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

Follow-Up and Monitoring Protocol

• Repeat complete blood count and ferritin at 8-10 weeks after initiating oral iron to assess therapeutic response. 1, 2
• Target ferritin >100 ng/mL to fully restore iron stores and prevent recurrence. 2
• Continue oral iron for 3 months after hemoglobin normalizes to achieve adequate ferritin levels. 2
• For high-risk groups (menstruating females, vegetarians, athletes, regular blood donors), schedule ferritin screening every 6-12 months to detect early depletion before anemia develops. 2

Critical Pitfalls to Avoid

• Do not overlook celiac disease screening—its 3-5% prevalence in iron-deficiency cases leads to treatment failure if missed. 1, 2
• Do not assume normal ferritin excludes iron deficiency in inflammatory states; check transferrin saturation (<20% confirms deficiency). 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 delay endoscopic evaluation in high-risk patients (age ≥50, alarm symptoms, treatment failure), as gastrointestinal malignancy can present solely with iron deficiency. 1, 2
• Do not perform extensive GI investigation in young, asymptomatic premenopausal women with heavy menses—the diagnostic yield is extremely low (0-6.5%). 1
• Normal total iron-binding capacity does not exclude iron deficiency; it must be interpreted alongside ferritin, serum iron, and inflammatory markers. 1