What is the appropriate management for a patient with decreased ferritin levels, indicating potential iron deficiency or depletion?

Management of Decreased Ferritin Levels

Initiate oral iron supplementation immediately with ferrous sulfate 325 mg daily or on alternate days, while simultaneously investigating the underlying cause of iron deficiency, particularly gastrointestinal blood loss in men and postmenopausal women. 1

Diagnostic Thresholds and Interpretation

The diagnosis of iron deficiency depends critically on ferritin levels and clinical context:

• Ferritin <15 μg/L has 99% specificity for absolute iron deficiency and confirms the diagnosis definitively 2, 3
• Ferritin <30 μg/L generally indicates depleted iron stores and warrants treatment, even in the absence of anemia 3, 4
• Ferritin <45 μg/L provides optimal sensitivity-specificity balance (specificity 0.92) for clinical decision-making and may justify gastrointestinal investigation 3

Critical Caveat: Rule Out Inflammation First

Ferritin is an acute-phase reactant that rises during inflammation, infection, or tissue damage, potentially masking true iron deficiency 3. In patients with inflammatory conditions (IBD, CKD, heart failure), the diagnostic threshold shifts upward to ferritin <100 μg/L 3, 1. Always check C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) when ferritin is 30-100 μg/L to determine if ferritin is falsely elevated 4.

Complementary Iron Studies Required

Never rely on ferritin alone—always calculate transferrin saturation (TSAT):

• TSAT <16-20% confirms iron deficiency (absolute or functional), even when ferritin appears normal 3, 1
• TSAT = (serum iron × 100) ÷ total iron-binding capacity 3
• Low TSAT reflects insufficient iron available for red blood cell production 3

Investigation Algorithm Based on Patient Population

For Premenopausal Women with Heavy Menses

GI investigation is not mandatory unless red flags are present 3. The appropriate approach includes:

• Screen for celiac disease with tissue transglutaminase (tTG) antibodies, as celiac disease is present in 3-5% of iron deficiency cases 2, 3
• Test for H. pylori non-invasively (stool antigen or urea breath test) 2, 3
• Assess menstrual blood loss history, as this is the most common cause in premenopausal women 3
• Reserve bidirectional endoscopy for: age ≥50 years, GI symptoms (abdominal pain, change in bowel habits, blood in stool), positive celiac/H. pylori testing, failure to respond to adequate oral iron after 8-10 weeks, or strong family history of colorectal cancer 3

For Men and Postmenopausal Women

Bidirectional endoscopy should be performed, as recurrent blood loss is responsible for 94% of cases and 9% of patients older than 65 years with iron deficiency anemia have gastrointestinal cancer 5, 6. Begin with colonoscopy if the patient is older than 50 6.

• Screen for celiac disease and H. pylori in all patients 2
• Document use of aspirin and NSAIDs, as these are common causes of iron deficiency 2

First-Line Treatment: Oral Iron Supplementation

Start oral iron immediately without waiting for investigation results 3:

• Ferrous sulfate 325 mg daily or on alternate days (containing 65 mg elemental iron per tablet) 1, 5
• Alternate-day dosing (60 mg elemental iron every other day) may improve absorption and reduce gastrointestinal side effects compared to daily dosing 3, 5
• Take on empty stomach for optimal absorption, or with meals if gastrointestinal symptoms occur 3
• Expected side effects include constipation, nausea, or diarrhea, affecting approximately 50% of patients and reducing adherence 5

When to Use Intravenous Iron Instead

Intravenous iron is indicated for 1, 5:

• Oral iron intolerance or poor absorption (celiac disease, post-bariatric surgery)
• Chronic inflammatory conditions (CKD, heart failure, IBD, cancer)
• Ongoing blood loss that cannot be controlled
• Second and third trimesters of pregnancy
• Heart failure patients, where IV iron increases exercise capacity
• Failure to respond to adequate oral iron therapy after 8-10 weeks

Follow-Up and Monitoring

Repeat CBC and ferritin in 8-10 weeks to assess response to treatment 3, 4:

• Expect hemoglobin increase of 1-2 g/dL within one month if treatment is effective 6
• Target ferritin >100 ng/mL to restore iron stores and prevent recurrence 3
• If no improvement, consider malabsorption, non-compliance, ongoing blood loss, or need for IV iron 3

For patients with recurrent low ferritin (menstruating females, vegetarians, athletes, blood donors):

• Screen ferritin every 6-12 months depending on risk factors 3, 4
• Do not continue daily iron supplementation once ferritin normalizes, as this is potentially harmful 3, 4

Common Pitfalls to Avoid

• Never assume normal ferritin excludes iron deficiency—always check TSAT, as functional iron deficiency can occur with normal ferritin but low TSAT 3
• Never overlook celiac disease, which is easily missed without serologic screening and present in 3-5% of iron deficiency cases 2, 3
• Never perform extensive GI investigation in young, asymptomatic premenopausal women with heavy menses, as the yield is extremely low (0-6.5%) 3
• Never continue long-term daily oral or IV iron supplementation when ferritin is normal or high, as this is potentially harmful 4
• Never ignore inflammation markers—ferritin can be falsely elevated in inflammatory states, masking true iron deficiency 3, 4