What is the best course of action for a patient with iron deficiency anemia, characterized by low ferritin (31) and iron saturation levels?

Management of Iron Deficiency with Ferritin 31 ng/mL and Low Iron Saturation

Start oral iron supplementation immediately with ferrous sulfate 325 mg (65 mg elemental iron) on alternate days, as this ferritin level definitively confirms iron deficiency requiring treatment. 1, 2

Diagnostic Confirmation

Your ferritin of 31 ng/mL with low iron saturation unequivocally confirms iron deficiency, as ferritin <30-45 ng/mL is diagnostic regardless of inflammation status. 1, 3 The low transferrin saturation (<20%) provides additional confirmation of depleted iron stores. 1, 2

Immediate Treatment Protocol

Oral iron is first-line therapy for uncomplicated iron deficiency:

• Prescribe ferrous sulfate 325 mg (65 mg elemental iron) on alternate days rather than daily dosing, as this improves absorption and reduces gastrointestinal side effects. 1, 3, 4

• If alternate-day dosing is not tolerated, use 100-200 mg elemental iron daily in divided doses. 1

• Advise taking iron with vitamin C or on an empty stomach to enhance absorption. 1

• Avoid taking iron with proton pump inhibitors, H2-blockers, or calcium supplements, which impair absorption. 5

Essential Workup for Underlying Cause

You must investigate the source of iron deficiency based on patient demographics:

• For premenopausal women: Assess for heavy menstrual bleeding as the primary cause. 1, 4

• For men and postmenopausal women: Perform bidirectional endoscopy to investigate gastrointestinal bleeding, as recurrent blood loss accounts for 94% of cases. 1, 3

• Before endoscopy: Order non-invasive testing for H. pylori infection and celiac disease, as both commonly cause iron deficiency. 1, 3, 4

• Check for dietary insufficiency: Particularly in vegetarians/vegans where iron bioavailability is substantially lower. 2

Monitoring Response to Treatment

Reassess hemoglobin and iron studies in 2-4 weeks after initiating oral iron. 1, 3

• Expected response: Hemoglobin should increase by 1-2 g/dL within 4 weeks. 1

• If no response after 4 weeks: Switch to intravenous iron, as lack of response indicates either non-compliance, malabsorption, ongoing blood loss, or inflammation-mediated hepcidin upregulation blocking iron absorption. 5, 1

• Only 21% of oral iron non-responders will respond to continued oral therapy, compared to 65% who respond to IV iron. 5

Treatment Goals and Duration

Continue iron supplementation for 3-6 months after hemoglobin normalizes to fully restore iron stores:

• Target hemoglobin >12 g/dL for women and >13 g/dL for men. 1

• Target ferritin >100 ng/mL to replenish iron stores. 1, 2

• Re-treat if ferritin drops below 100 ng/mL after successful treatment. 2

When to Use Intravenous Iron Instead

Switch to IV iron if:

• No hemoglobin response after 4 weeks of oral iron. 1, 3

• Intolerance to oral iron (occurs in approximately 50% of patients). 3, 4

• Active inflammatory bowel disease with compromised absorption. 5, 2

• Post-bariatric surgery with anatomical changes limiting absorption. 2, 4

• Ongoing blood loss that cannot be immediately controlled. 5, 4

• Congestive heart failure (IV iron improves exercise capacity and outcomes). 5, 3, 4

• Second or third trimester of pregnancy. 4

Critical Pitfalls to Avoid

Do not miss occult gastrointestinal bleeding: Always investigate GI sources in men and postmenopausal women, as this represents the most common cause requiring urgent identification. 2, 3

Do not continue oral iron indefinitely without response: After 4 weeks of no improvement, switch to IV iron rather than persisting with oral therapy. 5, 1

Do not overlook inflammation: If CRP or ESR is elevated, ferritin can be falsely elevated, and transferrin saturation <20% becomes the more reliable marker. 1, 2

Do not supplement iron if ferritin normalizes without ongoing risk factors: Long-term daily iron supplementation with normal ferritin is potentially harmful. 6