What are the implications and treatment options for a patient with a decreased ferritin level, potentially indicating iron deficiency anemia?

Management of Decreased Ferritin Level

All patients with decreased ferritin should receive oral iron supplementation to correct deficiency and replenish body stores, with ferrous sulfate 200 mg three times daily (or 324 mg tablets containing 65 mg elemental iron) as the first-line treatment. 1, 2

Diagnostic Thresholds and Interpretation

Ferritin <15 μg/L has 99% specificity for absolute iron deficiency and definitively confirms the diagnosis, requiring immediate investigation for the source of iron loss. 3, 4

• Ferritin 15-30 μg/L indicates depleted iron stores and warrants treatment even without anemia 3
• Ferritin <45 μg/L provides optimal sensitivity-specificity balance (92% specificity) for clinical decision-making 3
• In patients with inflammation, chronic kidney disease, heart failure, or inflammatory bowel disease, the diagnostic threshold shifts upward to ferritin <100 μg/L 3, 5

Critical Caveat: Rule Out Inflammation

Ferritin is an acute-phase reactant that rises during infection, inflammation, or tissue damage, potentially masking true iron deficiency. 3, 6

• Check CRP and ESR when ferritin is 30-100 μg/L to identify mixed iron deficiency (absolute + functional) 3
• Calculate transferrin saturation (TSAT = serum iron × 100 ÷ TIBC): values <16-20% confirm iron deficiency even with higher ferritin 3, 4

Investigation Strategy

For Premenopausal Women

GI investigation is not mandatory for young premenopausal women with heavy menstrual bleeding unless red flags are present. 3

• Perform non-invasive testing for H. pylori (stool antigen or urea breath test) and celiac disease (tissue transglutaminase antibodies) 3, 4
• If testing is negative and patient is young with heavy menses, empiric iron supplementation alone is reasonable 3

Reserve bidirectional endoscopy for: 3

• Age ≥50 years (higher risk of GI malignancy)
• Positive H. pylori or celiac testing requiring confirmation
• GI symptoms (abdominal pain, change in bowel habits, blood in stool)
• Failure to respond to adequate oral iron after 8-10 weeks

For Men and Postmenopausal Women

Bidirectional endoscopy should be performed, as recurrent blood loss is responsible for 94% of cases. 1, 4 Upper GI endoscopy with small bowel biopsy and colonoscopy are indicated to identify occult GI bleeding sources. 1

Iron Supplementation Protocol

First-Line: Oral Iron

Initiate ferrous sulfate 200 mg (65 mg elemental iron) three times daily immediately. 1, 2

• Alternate-day dosing (60 mg every other day) may improve absorption and reduce GI side effects compared to daily dosing 3, 5
• Take on empty stomach for optimal absorption, or with meals if GI symptoms occur 3
• Ascorbic acid enhances iron absorption and should be considered when response is poor 1
• Expected side effects include constipation, nausea, or diarrhea (50% of patients have decreased adherence) 4

When to Use Intravenous Iron

Parenteral iron should only be used when there is intolerance to at least two oral preparations or non-compliance. 1

Intravenous iron is specifically indicated for: 4, 5

• Oral iron intolerance or poor absorption (celiac disease, post-bariatric surgery)
• Chronic inflammatory conditions (CKD, heart failure, IBD, cancer)
• Ongoing blood loss
• Second and third trimesters of pregnancy
• Heart failure patients (to increase exercise capacity)

Parenteral iron is painful when given intramuscularly, expensive, and may cause anaphylactic reactions (though <1% with newer formulations). 1, 4

Follow-Up and Monitoring

Hemoglobin should rise by 2 g/dL after 3-4 weeks of treatment. 1

• Repeat CBC and ferritin in 8-10 weeks (or 2-4 weeks per recent guidelines) to assess response 3, 4
• Target ferritin >100 ng/mL to restore iron stores and prevent recurrence 3
• Continue iron supplementation for three months after correction of anemia to replenish body stores 1

Failure to respond indicates: 1

• Poor compliance (most common)
• Misdiagnosis
• Continued blood loss
• Malabsorption

Long-Term Surveillance

Monitor hemoglobin and red cell indices every 3 months for one year, then after a further year. 1

• For high-risk populations (menstruating females, vegetarians, athletes, blood donors), screen ferritin every 6-12 months 3
• Do not continue daily iron supplementation once ferritin normalizes, as this is potentially harmful 3
• Additional oral iron should be given if hemoglobin or MCV falls below normal 1

Common Pitfalls to Avoid

• Do not assume normal ferritin excludes iron deficiency—transferrin saturation is the key parameter for assessing iron availability for erythropoiesis 3
• Do not perform extensive GI investigation in young, asymptomatic premenopausal women with heavy menses—the yield is extremely low (0-6.5%) 3
• Do not overlook celiac disease, which is present in 3-5% of iron deficiency cases and requires serologic screening 3
• Faecal occult blood testing is of no benefit, being insensitive and non-specific 1