In a 15-year-old female with microcytic anemia (MCV 66 fL, RBC 6.03 ×10⁶/µL, RDW 16.6 %, serum iron 45 µg/dL), what is the next diagnostic step to differentiate iron‑deficiency anemia from β‑thalassemia trait and which medication should be ordered if iron deficiency is confirmed?

Next Diagnostic Step and Treatment for Microcytic Anemia in a 15-Year-Old Female

Immediate Next Step: Order Serum Ferritin and Transferrin Saturation

The next diagnostic step is to order serum ferritin and transferrin saturation (TSAT) to definitively distinguish iron-deficiency anemia from β-thalassemia trait. 1

Why These Tests Are Essential

• Serum ferritin <30 μg/L confirms iron deficiency and effectively excludes thalassemia trait, as thalassemia patients maintain normal or elevated iron stores. 1

• The combination of elevated RDW (16.6%) with severe microcytosis (MCV 66.2 fL) strongly favors iron-deficiency anemia over β-thalassemia trait, because thalassemia typically presents with RDW ≤14% due to uniformly small red cells. 1, 2

• Transferrin saturation <16–20% confirms iron deficiency, particularly when ferritin might be falsely elevated by inflammation (note the elevated ESR of 36). 1

Interpreting the Current Laboratory Pattern

The patient's profile already suggests iron deficiency:

• Low serum iron (45 μg/dL) combined with elevated ESR (36 mm/hr) and elevated RDW (16.6%) is characteristic of iron-deficiency anemia, not thalassemia trait. 1

• The markedly elevated RBC count (6.03 ×10⁶/µL) might initially suggest thalassemia, but when combined with high RDW and low serum iron, iron deficiency remains more likely. 1, 3

• Approximately 50% of thalassemia cases can show elevated RDW, but the concurrent presence of high RDW, low serum iron, and elevated ESR makes iron deficiency the predominant diagnosis. 1

Diagnostic Algorithm

Step 1: Obtain Ferritin and TSAT

• If ferritin <30 μg/L and TSAT <20% → Confirmed iron-deficiency anemia; proceed to treatment and investigate source of blood loss. 1

• If ferritin >30 μg/L with normal TSAT (>20%) → Order hemoglobin electrophoresis to evaluate for β-thalassemia trait. 1

• If ferritin 30–100 μg/L (borderline) → TSAT <16–20% still confirms iron deficiency despite borderline ferritin, especially given the elevated ESR suggesting inflammation. 1

Step 2: Consider C-Reactive Protein (CRP)

• Measure CRP concurrently because ferritin is an acute-phase reactant that can be falsely elevated by inflammation; the patient's ESR of 36 suggests this may be relevant. 1, 3

Step 3: Reserve Hemoglobin Electrophoresis for Specific Indications

• Order hemoglobin electrophoresis only if iron studies are normal or borderline, or if the patient belongs to a high-risk ethnic group (African, Mediterranean, Southeast Asian ancestry). 1

• Do not use hemoglobin electrophoresis as a first-line test; it is unnecessary when iron studies are clearly abnormal. 1

Medication to Order: Oral Iron Supplementation

If iron deficiency is confirmed (ferritin <30 μg/L or TSAT <20%), initiate ferrous sulfate 200 mg three times daily for at least three months after correction of anemia to replenish iron stores. 1

Treatment Details

• Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated due to gastrointestinal side effects. 1

• Adding ascorbic acid (vitamin C) enhances iron absorption and may improve efficacy. 1

• A hemoglobin rise ≥10 g/L within 2 weeks confirms iron deficiency as the diagnosis and validates the treatment approach. 1

Monitoring Response

• Monitor hemoglobin and red cell indices at three-monthly intervals for one year, then reassess after an additional year. 1

• If hemoglobin or MCV falls below normal during follow-up, provide additional oral iron supplementation. 1

Critical Next Step: Investigate Source of Iron Loss

In a 15-year-old female, the two most common causes of iron deficiency are heavy menstrual bleeding and gastrointestinal blood loss. 1

Mandatory Evaluation

• Obtain a detailed menstrual history to assess for heavy menstrual bleeding (menorrhagia), which is the most common cause in premenopausal adolescents. 1

• Screen for dietary inadequacy, particularly vegetarian or vegan eating patterns, which increase the risk of iron deficiency in adolescents. 1

• Evaluate for gastrointestinal blood loss through history of melena, hematochezia, or occult bleeding, even in adolescents. 1

• Consider celiac disease screening if malabsorption is suspected, as it accounts for 2–3% of iron-deficiency anemia cases. 1

Common Pitfalls to Avoid

• Do not assume thalassemia based solely on ethnic background without laboratory confirmation; hemoglobinopathies must be confirmed by testing, not presumed. 3

• Do not rely on serum iron alone, as it shows considerable day-to-day variability and overlaps between iron deficiency and thalassemia. 1

• Do not overlook combined deficiencies; iron deficiency can coexist with vitamin B12 or folate deficiency, which may also cause elevated RDW. 1, 2

• Do not attribute iron deficiency solely to dietary insufficiency in adolescents; occult gastrointestinal blood loss must be excluded even in young patients. 1

• Recognize that approximately 50% of thalassemia cases can show elevated RDW, but the combination of high RDW, low serum iron, and elevated ESR makes iron deficiency far more likely in this patient. 1