What is the best treatment for a patient with iron deficiency anemia and low ferritin level?

Treatment of Iron Deficiency Anemia with Severely Depleted Iron Stores

Start oral ferrous sulfate 325 mg (65 mg elemental iron) three times daily and continue for three months after hemoglobin normalizes to fully replenish iron stores. 1

Diagnosis Confirmation

Your patient has confirmed iron deficiency anemia:

• Ferritin of 6 ng/mL is well below the diagnostic threshold of 45 ng/mL recommended by the American Gastroenterological Association for patients with anemia 2
• Hemoglobin of 14.5 g/dL appears normal now, but the severely depleted ferritin indicates the patient has exhausted iron stores and requires aggressive repletion 1
• The negative stool occult blood test and normal endoscopic evaluations suggest the iron deficiency is likely from chronic low-grade losses (possibly menstrual if premenopausal) or malabsorption rather than active GI bleeding 2

First-Line Treatment: Oral Iron Therapy

Initiate ferrous sulfate 325 mg (containing 65 mg elemental iron) three times daily, which is the AGA-recommended first-line treatment due to its effectiveness, simplicity, and low cost 1. Each 324-325 mg tablet provides 65 mg of elemental iron 3.

Dosing Strategy and Alternatives

• Standard dosing is 100-200 mg elemental iron daily in divided doses, which translates to 2-3 tablets of ferrous sulfate 325 mg daily 2
• Recent evidence suggests alternate-day dosing may improve absorption and reduce gastrointestinal side effects, though this is a newer approach 2
• If gastrointestinal side effects occur (nausea, constipation, abdominal pain), consider switching to ferrous gluconate or ferrous fumarate, which are equally effective 1
• Liquid preparations may be better tolerated than tablets if side effects persist 1
• Adding vitamin C (ascorbic acid) to oral iron can enhance absorption in patients with poor response 1

Critical Treatment Duration

Continue iron therapy for three full months AFTER hemoglobin normalizes to adequately replenish iron stores 1. This is a common pitfall—many clinicians stop treatment once anemia resolves, but with a ferritin of 6 ng/mL, your patient needs extended therapy to rebuild stores and prevent rapid recurrence 1.

Monitoring Response

• Expect hemoglobin to rise by approximately 2 g/dL after 3-4 weeks of therapy 1
• Recheck complete blood count and ferritin after 8-10 weeks of treatment 2, 4
• Do not check ferritin earlier, as levels can be falsely elevated immediately after starting supplementation 2
• Once hemoglobin normalizes, monitor every 3 months for one year, then annually 1
• If hemoglobin or MCV falls below normal during monitoring, restart oral iron supplementation 1

Failure to Respond

If hemoglobin does not rise appropriately after 3-4 weeks, consider:

• Poor compliance with medication 1
• Continued occult blood loss 1
• Malabsorption (consider celiac disease testing if not already done, H. pylori testing) 2
• Need for intravenous iron 1

When to Use Intravenous Iron

Reserve IV iron for specific situations only 1:

• Intolerance to at least two different oral iron preparations 1
• Non-compliance with oral therapy 1
• Malabsorption conditions (celiac disease, post-bariatric surgery) 5
• Chronic inflammatory conditions with active inflammation (inflammatory bowel disease, chronic kidney disease, heart failure) 2, 5
• Ongoing blood loss unresponsive to oral iron 2

If IV iron becomes necessary, administer 1 gram of iron as a single dose using ferric carboxymaltose or similar modern carbohydrate-bound formulation over 15 minutes 2. High molecular weight iron dextran carries the highest risk of infusion reactions and should be avoided 2.

Investigating the Underlying Cause

Given normal endoscopy in 2023 and negative stool occult blood:

• If premenopausal woman: heavy menstrual bleeding affects 5-10% of menstruating women and is the most common cause 1
• Consider dietary assessment for inadequate iron intake or vegetarian/vegan diet 4
• Evaluate for malabsorption: ensure H. pylori and celiac testing were completed 2
• Review medications: NSAIDs, proton pump inhibitors, antacids can contribute 5

Critical Pitfalls to Avoid

• Do not stop iron supplementation when hemoglobin normalizes—continue for three additional months to replenish stores 1
• Do not continue daily iron if ferritin becomes normal or elevated, as this is potentially harmful 2, 4
• Do not recheck ferritin before 8-10 weeks, as early testing yields falsely elevated results 2
• Do not assume normal endoscopy rules out all GI pathology—small bowel sources may have been missed, though with negative occult blood this is less likely 2

Long-Term Management

After completing the initial 3-month post-normalization treatment course:

• Patients with recurrent low ferritin benefit from intermittent oral supplementation to preserve iron stores 4
• Monitor with complete blood count and ferritin every 6-12 months 4
• Address underlying causes (menstrual management, dietary counseling) to prevent recurrence 4