What is the appropriate workup and management for low ferritin?

Workup and Management of Low Ferritin

Begin oral iron supplementation immediately with ferrous sulfate 65 mg elemental iron daily (or alternate-day dosing to improve absorption and reduce side effects), while concurrently screening for celiac disease and Helicobacter pylori infection, and reserve bidirectional endoscopy for high-risk patients (age ≥50 years, gastrointestinal symptoms, or treatment failure after 8-10 weeks). 1, 2, 3

Diagnostic Interpretation of Ferritin Levels

The ferritin threshold determines your diagnostic certainty and urgency of investigation:

• Ferritin <15 µg/L: This has 99% specificity for absolute iron deficiency—diagnosis is definitive, no additional testing needed to confirm iron depletion 1, 3
• Ferritin 15-30 µg/L: Indicates depleted iron stores requiring treatment 1, 3
• Ferritin 30-45 µg/L: Provides optimal sensitivity-specificity balance (92% specificity) for clinical decision-making 1, 3
• Ferritin 45-100 µg/L: May still represent iron deficiency if transferrin saturation (TSAT) <20%, particularly in inflammatory states 1, 4, 3

Critical Caveat: Ferritin as an Acute-Phase Reactant

Ferritin rises during inflammation, infection, or tissue damage, potentially masking true iron deficiency. 1, 2 In patients with chronic inflammatory conditions (inflammatory bowel disease, chronic kidney disease, heart failure, cancer), the diagnostic threshold shifts upward to ferritin <100 µg/L. 1, 3 Always check C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) when ferritin is 30-100 µg/L to determine if elevation is inflammatory rather than reflecting adequate stores. 1, 5

Essential Complementary Testing

Calculate transferrin saturation (TSAT) using the formula: (serum iron × 100) ÷ total iron-binding capacity. 1, 2 TSAT <16-20% confirms iron deficiency even when ferritin appears borderline or is elevated by inflammation. 1, 3 This combination distinguishes:

• Absolute iron deficiency: Low ferritin + low TSAT 1, 2
• Functional iron deficiency: Normal/elevated ferritin + low TSAT (iron sequestered, unavailable for erythropoiesis) 1, 2
• Anemia of chronic disease: Elevated ferritin + low TSAT + elevated CRP/ESR 1, 2

Mandatory Screening for Underlying Causes

Universal Screening (All Patients)

• Celiac disease: Order tissue transglutaminase IgA antibodies—celiac accounts for 3-5% of iron deficiency cases and causes treatment failure when missed 1, 2, 3
• Helicobacter pylori: Perform non-invasive testing (stool antigen or urea breath test) because the organism impairs iron absorption 1, 2, 3

Risk-Stratified Endoscopic Evaluation

Reserve bidirectional endoscopy (upper gastroscopy + colonoscopy) for: 1, 2, 3

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

In premenopausal women <50 years with heavy menstrual bleeding and no gastrointestinal symptoms, empiric oral iron supplementation without immediate endoscopy is appropriate. 1, 2 However, if treatment fails or symptoms develop, proceed to endoscopy. 1, 3

In adult men and postmenopausal women, urgent bidirectional endoscopy is mandatory because iron deficiency may be the sole manifestation of gastrointestinal malignancy. 1, 2

Oral Iron Supplementation Protocol

Initiate ferrous sulfate 65 mg elemental iron daily, or use alternate-day dosing (60-65 mg every other day) to improve absorption by 30-50% and reduce gastrointestinal side effects. 1, 2, 3 Take on an empty stomach for optimal absorption, or with meals if gastrointestinal symptoms occur. 1, 5

Expected Response and Monitoring

• Hemoglobin should rise by ≥10 g/L within 2 weeks of starting therapy 1, 2, 3
• Repeat complete blood count and ferritin at 8-10 weeks to assess response 1, 2, 3
• Continue oral iron for 3 months after hemoglobin normalizes to achieve target ferritin >100 ng/mL and prevent recurrence 1, 5, 6

Common Pitfall: Premature Discontinuation

Standard-dose oral iron does not raise ferritin until hemoglobin normalizes—ferritin replenishment requires 3-6 months of continued supplementation after anemia resolves. 6 Do not stop iron therapy once hemoglobin normalizes; an additional 3 months is required to restore ferritin >100 ng/mL. 1, 6

Indications for Intravenous Iron

Switch to intravenous ferric carboxymaltose (15 mg/kg, maximum 1000 mg per dose) when any of the following apply: 1, 2, 3

• Oral iron intolerance (severe 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 iron

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 these populations. 1, 2

Long-Term Monitoring for High-Risk Groups

For patients at risk of recurrent iron depletion (menstruating females, vegetarians, athletes, regular blood donors), schedule ferritin screening every 6-12 months to detect early depletion before anemia develops. 1, 5 Do not continue daily iron supplementation once ferritin normalizes, as this is potentially harmful. 1, 5

Critical Pitfalls to Avoid

• Do not assume normal ferritin excludes iron deficiency—TSAT is the key parameter for assessing iron availability when ferritin is 30-100 µg/L 1, 4
• Do not overlook celiac disease screening—its 3-5% prevalence in iron deficiency cases leads to treatment failure when missed 1, 2, 3
• Do not delay endoscopy in high-risk patients (age ≥50, alarm symptoms, treatment failure)—gastrointestinal malignancy can present solely with iron deficiency 1, 2
• Do not assume ferritin will normalize spontaneously after bleeding stops—dietary iron alone is insufficient to replenish stores within a clinically acceptable timeframe 1, 6