What is the best course of treatment for a postmenopausal patient in her late 50s with iron deficiency (ID), normal hemoglobin, fatigue, and achy feelings, who also has atrial fibrillation (Afib) and is on direct oral anticoagulant (DOAC) therapy?

Management of Iron Deficiency in a Postmenopausal Woman with Atrial Fibrillation on DOAC

Start oral iron supplementation with ferrous sulfate 200 mg once daily on an empty stomach to improve fatigue and replenish iron stores, while simultaneously investigating for gastrointestinal blood loss given the DOAC therapy. 1

Immediate Treatment Approach

Iron Supplementation Strategy

• Initiate ferrous sulfate 200 mg once daily as first-line therapy, taken on an empty stomach for optimal absorption 1, 2
• Once-daily dosing is preferred because oral iron increases serum hepcidin for up to 48 hours, blocking further absorption and increasing side effects without additional benefit 1, 3
• If gastrointestinal side effects occur (nausea, constipation, abdominal pain affect 8-12% of patients), switch to alternate-day dosing with 120 mg ferrous sulfate, which improves tolerance while maintaining effectiveness 1, 3
• Add vitamin C 500 mg with the iron dose to enhance absorption, especially important in this patient on DOAC therapy 1, 2
• Alternative ferrous salts (ferrous fumarate, ferrous gluconate) are equally effective if ferrous sulfate is not tolerated 1, 2

Expected Clinical Response

• Iron supplementation in iron-deficient non-anemic patients significantly reduces fatigue (standardized mean difference -0.38), which directly addresses this patient's primary complaint 4
• Hemoglobin should rise approximately 2 g/dL after 3-4 weeks if anemia develops 2, 5
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores—this is a critical step many clinicians miss 2, 5

Mandatory Gastrointestinal Investigation

Why Investigation is Essential in This Patient

• Postmenopausal women with iron deficiency require gastrointestinal evaluation because GI blood loss is the most common cause in this population 1, 6
• The DOAC therapy significantly increases the risk of occult GI bleeding, making investigation even more urgent 1
• Dual pathology (upper and lower GI bleeding sources) occurs in 1-10% of patients, with higher rates in older patients 1

Required Diagnostic Workup

• Upper endoscopy (esophagogastroduodenoscopy) with duodenal biopsies to exclude celiac disease, gastric/duodenal ulcers, and upper GI malignancy 1
• Colonoscopy to exclude colorectal cancer and other lower GI bleeding sources 1, 6
• Celiac serology (tissue transglutaminase antibody) should be checked at presentation 1, 2
• Test for Helicobacter pylori and eradicate if present, as it contributes to iron deficiency 1

Monitoring Protocol

Follow-up Timeline

• Recheck complete blood count and hemoglobin at 3-4 weeks to confirm response to oral iron 2, 5
• Do not reassess earlier than 4 weeks, as this may miss the expected response trajectory 2
• Monitor hemoglobin and red cell indices every 3 months for the first year 2
• Check ferritin levels to confirm iron store repletion after 3 months of therapy 1

When to Switch to Intravenous Iron

Indications for IV Iron

• Intolerance to at least two different oral iron preparations despite trying alternate-day dosing 2
• No hemoglobin rise after 4 weeks of adequate oral therapy 2
• Malabsorption conditions identified during workup (celiac disease, inflammatory bowel disease, post-bariatric surgery) 1
• Active inflammation with compromised absorption 1

IV Iron Administration

• Preferred formulation: ferric carboxymaltose 1000 mg over 15 minutes 2
• Resuscitation facilities must be available due to anaphylaxis risk 2
• Note: Iron carboxymaltose can cause prolonged hypophosphatemia with repeated dosing, leading to fatigue and osteomalacia—use cautiously in patients with poor nutrition 1

Critical Pitfalls to Avoid

Common Management Errors

• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores, as premature discontinuation leads to recurrence 2, 5
• Do not fail to investigate the underlying cause while treating with iron supplementation 2, 6
• Do not prescribe multiple daily doses—this increases side effects without improving absorption due to hepcidin elevation 1, 3
• Do not give iron in the afternoon or evening after a morning dose, as circadian hepcidin increases reduce absorption 3

Special Consideration for DOAC Therapy

• The combination of iron deficiency and DOAC therapy strongly suggests occult GI bleeding as the etiology 1
• Gastrointestinal investigation should not be delayed even if the patient responds to iron supplementation 1, 6
• Consider whether the DOAC is truly indicated or if the bleeding risk outweighs the stroke prevention benefit, though this requires cardiology consultation for formal risk-benefit analysis 1