In an otherwise healthy teenage girl with anemia, should I start empiric iron supplementation without first confirming iron deficiency and only perform a full work‑up if there is no hemoglobin response?

Empiric Iron Supplementation in Adolescent Girls with Anemia

Yes, you can start empiric iron supplementation in an otherwise healthy teenage girl with anemia, but you must confirm the diagnosis with a repeat hemoglobin after 4 weeks—a rise of ≥1 g/dL confirms iron deficiency, while failure to respond mandates a full work-up with additional laboratory tests. 1, 2

Why This Approach Is Guideline-Supported

The CDC explicitly permits a presumptive diagnosis of iron-deficiency anemia when an adolescent girl has a positive anemia screen and is not acutely ill. 1, 2 This strategy recognizes that iron deficiency is the most common cause of anemia in this population—accounting for roughly 50–64% of microcytic anemia in adolescent females. 2

Key Steps in the Empiric Treatment Protocol

1. Confirm the screening result by repeating hemoglobin or hematocrit before starting therapy. 1, 2

2. Initiate empiric iron therapy with 60–120 mg elemental iron daily, taken between meals to maximize absorption. 1, 2, 3

3. Provide dietary counseling emphasizing iron-rich foods (especially heme iron from meat, poultry, fish) and vitamin C co-ingestion to enhance absorption. 1, 2, 4

4. Recheck hemoglobin after 4 weeks—an increase of ≥1 g/dL (or hematocrit rise of ≥3%) confirms iron-deficiency anemia. 1, 2, 3

5. If confirmed, continue iron for an additional 2–3 months to replenish iron stores, then reassess hemoglobin approximately 6 months after therapy completion. 1, 2, 3

When to Perform the Full Work-Up

If hemoglobin does not rise by ≥1 g/dL after 4 weeks despite adherence, obtain additional laboratory tests including: 1, 2, 3

• Mean corpuscular volume (MCV) and red-cell distribution width (RDW) to differentiate iron deficiency from thalassemia trait (iron deficiency shows elevated RDW >14%; thalassemia trait shows normal RDW ≤14%). 2

• Serum ferritin—a level <15 µg/L confirms iron deficiency, while ≥15 µg/L suggests an alternative etiology. 1, 2

• C-reactive protein (CRP) to detect inflammation that can falsely elevate ferritin and mask iron deficiency. 2

Extended Testing for Persistent Non-Response

If the diagnosis remains unclear after these tests, measure: 2

• Vitamin B12 and folate to exclude megaloblastic anemia
• Haptoglobin and lactate dehydrogenase if hemolysis is suspected
• Hemoglobin electrophoresis in patients of African, Mediterranean, or Southeast Asian ancestry to detect thalassemia or other hemoglobinopathies

Consider hematology consultation if the etiology remains unclear after extended testing. 2

Common Pitfalls to Avoid

• Do not skip the 4-week hemoglobin recheck—this is the diagnostic confirmation step that determines whether you proceed with continued iron therapy or initiate a full work-up. 1, 2

• Do not stop iron as soon as hemoglobin normalizes—stores must be replenished with an additional 2–3 months of therapy. 1, 2, 3

• Do not assume all microcytic anemia is iron deficiency—thalassemia trait is common in at-risk populations and presents with low MCV but normal RDW. 2

• Do not rely on ferritin alone in the presence of inflammation—CRP should be measured, and ferritin values up to 100 µg/L may still be compatible with iron deficiency when inflammation is present. 2

Risk Factors That Support Empiric Treatment

Adolescent girls with the following risk factors are at particularly high risk for iron deficiency and are ideal candidates for empiric therapy: 1, 2, 4

• Heavy or prolonged menstrual bleeding (the leading risk factor)
• Low dietary iron intake or restrictive diets (vegetarian, vegan, low red-meat intake)
• Prior history of iron-deficiency anemia
• High-impact or endurance sports participation

Optimizing Absorption and Adherence

• Administer iron between meals to maximize absorption; if gastrointestinal side effects occur, take with meals despite reduced absorption. 2, 4

• Recommend vitamin C-rich foods or supplements with iron to enhance absorption. 2, 4

• Consider a different iron formulation (ferrous gluconate or ferrous fumarate) or a liquid preparation if tablets are not tolerated. 4

• Use preparations with reasonable elemental iron content (28–50 mg) to prevent reduced compliance from gastrointestinal side effects. 5