How do I treat low ferritin in a patient with normal hemoglobin?

Treatment of Low Ferritin with Normal Hemoglobin

Start oral iron supplementation immediately with ferrous sulfate 65 mg elemental iron daily (or 60 mg on alternate days) to replenish depleted iron stores, regardless of normal hemoglobin, because low ferritin represents early-stage iron deficiency that causes symptoms and will progress to anemia if untreated. 1, 2, 3

Understanding the Clinical Significance

Low ferritin with normal hemoglobin represents Stage 1 iron deficiency—the earliest phase where iron stores are depleted but anemia has not yet developed. 1 This pattern warrants immediate intervention because:

• Ferritin <15 μg/L has 99% specificity for absolute iron deficiency and confirms diagnosis definitively 4, 1
• Ferritin 15-30 μg/L indicates depleted body iron stores requiring treatment 4, 1
• Ferritin <35 μg/L defines iron deficiency in athletes and menstruating women 1, 2
• Depleted iron stores cause significant symptoms—including fatigue, exercise intolerance, difficulty concentrating, restless legs syndrome, and pica—even before anemia develops 1, 3

Immediate Oral Iron Therapy

Initiate oral ferrous sulfate 65 mg elemental iron daily (equivalent to ferrous sulfate 325 mg) or 60 mg on alternate days. 1, 2, 3

• Alternate-day dosing (60 mg every other day) improves absorption by 30-50% and reduces gastrointestinal side effects compared to daily dosing 1, 5
• Take on an empty stomach for optimal absorption, or with meals if gastrointestinal symptoms occur 1
• Adding vitamin C 500 mg with each iron dose enhances absorption 2
• Expected side effects include constipation, nausea, or diarrhea, which can be minimized by taking with food or switching to alternate-day dosing 1

Alternative oral formulations if ferrous sulfate is not tolerated include ferrous bisglycinate 30-60 mg elemental iron daily or ferrous gluconate/fumarate at equivalent doses. 4, 5

Mandatory Investigation for Underlying Causes

Screen all patients for celiac disease and Helicobacter pylori infection because these conditions impair iron absorption and cause treatment failure. 1, 3

• Perform tissue transglutaminase IgA antibodies for celiac disease—present in 3-5% of iron-deficiency cases 1
• Test for H. pylori with stool antigen or urea-breath test 1, 3

Gastrointestinal Evaluation Criteria

Reserve bidirectional endoscopy (upper GI gastroscopy + colonoscopy) for specific high-risk situations: 1

• Age ≥50 years (higher malignancy risk)
• Gastrointestinal symptoms (abdominal pain, altered bowel habits, visible blood)
• Positive celiac or H. pylori testing requiring confirmation
• Failure to respond to adequate oral iron after 8-10 weeks
• Strong family history of colorectal cancer

For premenopausal women <50 years with heavy menstrual bleeding and no GI symptoms, empiric oral iron supplementation without immediate endoscopy is appropriate. 1

Additional Screening

Check inflammatory markers (CRP, ESR) if ferritin is 30-100 μg/L to exclude anemia of chronic disease masking true iron deficiency. 1 Calculate transferrin saturation (TSAT = [serum iron × 100] ÷ TIBC); values <16-20% confirm iron deficiency even with higher ferritin. 1

Follow-Up and Monitoring

Recheck complete blood count and ferritin at 8-10 weeks after initiating oral iron—not earlier, as ferritin may be falsely elevated immediately after supplementation. 1, 2, 6

• Expected response: hemoglobin should rise by ≥10 g/L within 2 weeks 1
• Target ferritin >100 ng/mL to fully replenish iron stores and prevent recurrence 1
• Continue oral iron for 3 months after hemoglobin normalizes to restore ferritin levels 4, 1

For high-risk populations (menstruating females, vegetarians, athletes, regular blood donors), schedule ferritin screening every 6-12 months. 1, 2

Indications for Intravenous Iron

Switch to intravenous ferric carboxymaltose (15 mg/kg, maximum 1000 mg per dose) when any of the following apply: 1, 7, 3

• Oral iron intolerance (severe nausea, constipation, diarrhea)
• Confirmed malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery)
• Ongoing blood loss exceeding oral replacement capacity
• Chronic inflammatory conditions (chronic kidney disease, heart failure, cancer)
• Pregnancy in the second or third trimester
• Failure to respond to adequate oral iron after 8-10 weeks

IV iron produces reticulocytosis within 3-5 days and yields a mean hemoglobin increase of approximately 8 g/L over 8 days, demonstrating superior efficacy in these populations. 1

Critical Pitfalls to Avoid

• Do not assume normal hemoglobin excludes the need for treatment—low ferritin alone causes significant symptoms and will progress to anemia if untreated 1, 3
• Do not overlook celiac disease screening—its 3-5% prevalence in iron-deficiency cases leads to treatment failure when missed 1
• Do not discontinue iron therapy once hemoglobin normalizes—continue for an additional 3 months to achieve ferritin >100 ng/mL 4, 1
• Do not continue daily iron supplementation once ferritin normalizes—this is potentially harmful and unnecessary 1
• Do not delay endoscopic evaluation in high-risk patients (age ≥50, alarm symptoms, treatment failure)—gastrointestinal malignancy can present solely with iron deficiency 1