What interventions are recommended for a patient with iron deficiency anemia, low iron saturation, and low ferritin levels?

Iron Deficiency Without Anemia: Initiate Oral Iron Supplementation

Based on your laboratory values showing iron deficiency (ferritin 21 ng/mL, transferrin saturation 16%, normal hemoglobin 15.1 g/dL), you should start oral iron supplementation with ferrous sulfate 325 mg daily or every other day, and investigate the underlying cause of iron depletion. 1, 2

Diagnostic Interpretation

Your labs confirm absolute iron deficiency without anemia:

• Ferritin 21 ng/mL is below the diagnostic threshold of <30 μg/L, confirming depleted iron stores 1
• Transferrin saturation 16% is at the lower limit (<16-20%), indicating insufficient iron delivery for erythropoiesis 1
• Hemoglobin 15.1 g/dL is normal, meaning you have nonanemic iron deficiency 3
• Your B12 and folate are adequate, ruling out other nutritional deficiencies 2

The ferritin <30 μg/L threshold has optimal sensitivity-specificity for diagnosing iron deficiency in patients without inflammation 1. Since you lack signs of inflammation (which would require ferritin <100 μg/L as the diagnostic cutoff), your low ferritin definitively confirms iron deficiency 1, 2.

Mandatory Investigation of Underlying Cause

You must investigate the source of iron depletion before simply treating with supplementation. The most critical step is determining why you are iron deficient:

Primary Causes to Investigate:

• Gastrointestinal bleeding accounts for 94% of iron deficiency cases in men and postmenopausal women and must be excluded 2, 3
• Menstrual blood loss is the leading cause in premenopausal women (38% have iron deficiency without anemia) 3
• Dietary insufficiency, particularly in vegetarians/vegans where iron bioavailability is substantially lower 1
• Malabsorption disorders including celiac disease, atrophic gastritis, H. pylori infection, or post-bariatric surgery 2, 3

Recommended Diagnostic Workup:

• For men and postmenopausal women: Bidirectional endoscopy (gastroscopy and colonoscopy) is indicated to rule out gastrointestinal malignancy or bleeding sources 2, 4
• For premenopausal women with heavy menstrual bleeding: Treat the bleeding source and provide iron supplementation; endoscopy may be deferred if this is the clear etiology 2
• All patients: Noninvasive testing for H. pylori infection and celiac disease serology, as both are common treatable causes 2, 4

First-Line Treatment: Oral Iron Supplementation

Start oral ferrous sulfate as first-line therapy:

• Dose: 325 mg ferrous sulfate (65 mg elemental iron) daily 5, 2, 3
• Alternative dosing: 60-65 mg elemental iron every other day improves absorption and reduces gastrointestinal side effects compared to daily dosing 1, 2
• Duration: Continue until ferritin normalizes (typically >30-50 μg/L) and for 3-6 months thereafter to replenish stores 2

The every-other-day dosing strategy is particularly important because approximately 50% of patients have decreased adherence due to gastrointestinal adverse effects (nausea, constipation, abdominal discomfort) with daily dosing 2.

Monitoring Response to Treatment

Evaluate response in 2-4 weeks:

• Recheck hemoglobin, ferritin, and transferrin saturation 2
• Expected response: Hemoglobin should increase by 1-2 g/dL within 2-4 weeks if treatment is effective 2
• Ferritin should gradually rise toward normal range 1

If inadequate response occurs, consider:

• Poor adherence due to side effects 2
• Ongoing blood loss exceeding iron replacement 3
• Malabsorption preventing adequate oral iron uptake 3
• Incorrect diagnosis (anemia of chronic disease masquerading as iron deficiency) 2

When to Use Intravenous Iron Instead

Switch to intravenous iron if:

• Intolerance to oral iron with significant gastrointestinal side effects 2, 3
• Malabsorption conditions (celiac disease, post-bariatric surgery, inflammatory bowel disease) 3
• Ongoing blood loss that cannot be controlled 3
• Failure to respond to adequate trial of oral iron 2
• Chronic inflammatory conditions (CKD, heart failure, IBD, cancer) where oral absorption is impaired 3

Hypersensitivity reactions to newer intravenous iron formulations are rare (<1%), making this a safe alternative when oral iron fails 2.

Ongoing Monitoring Strategy

After successful treatment:

• Menstruating females: Screen with ferritin every 6 months due to high risk of recurrence 1
• Males: Annual ferritin assessment 1
• Vegetarians/vegans: Enhanced vigilance with more frequent monitoring due to lower dietary iron bioavailability 1
• Re-treat when ferritin drops below 100 μg/L after successful treatment to prevent recurrence 1

Critical Pitfalls to Avoid

• Never assume dietary insufficiency alone without investigating for occult bleeding, especially in men and postmenopausal women 1, 2
• Do not ignore the need for endoscopy when indicated—iron deficiency may be the only clue to gastrointestinal malignancy 4
• Do not continue oral iron indefinitely without monitoring response—failure to respond warrants investigation for malabsorption or ongoing blood loss 2
• Do not overlook celiac disease and H. pylori testing, as these are common, treatable causes that will prevent iron repletion if left untreated 2, 4