What is the recommended evaluation and treatment for an adolescent female with serum iron 45 µg/dL, microcytic hypochromic anemia, elevated red‑cell count, and concurrent vitamin D deficiency?

Immediate Diagnostic Confirmation and Treatment for Iron-Deficiency Anemia

Begin oral iron supplementation with ferrous sulfate 325 mg once to three times daily immediately, while simultaneously ordering serum ferritin and transferrin saturation to confirm iron deficiency and investigating the underlying cause of blood loss. 1

Laboratory Interpretation

Your patient's serum iron of 45 µg/dL is low (normal range approximately 60–170 µg/dL in adults), and when combined with microcytic hypochromic anemia and an elevated red-cell count, this pattern strongly indicates iron-deficiency anemia rather than thalassemia trait. 2

Key Diagnostic Tests to Order Now

• Serum ferritin is the single most powerful test for confirming iron deficiency; a level <30 µg/L confirms depleted iron stores, while a cut-off of 45 µg/L provides optimal sensitivity and specificity in clinical practice. 1, 3

• Transferrin saturation (TSAT) should be calculated as (serum iron ÷ total iron-binding capacity) × 100; a value <16–20% confirms iron-deficient erythropoiesis even when ferritin may be falsely elevated by inflammation. 1, 3

• Red-cell distribution width (RDW) combined with mean corpuscular volume (MCV) distinguishes iron deficiency from thalassemia: a low MCV with RDW >14% indicates iron-deficiency anemia, whereas RDW ≤14% suggests thalassemia minor. 2, 1

• C-reactive protein (CRP) must be measured concurrently because ferritin is an acute-phase reactant that can be falsely elevated by inflammation, infection, malignancy, or hepatic disease. 1

Immediate Treatment Protocol

• Start ferrous sulfate 325 mg (65 mg elemental iron) once to three times daily on an empty stomach; a hemoglobin rise ≥10 g/L within 2 weeks confirms iron-deficiency anemia even when initial iron studies are equivocal. 1

• Adding ascorbic acid (vitamin C) 250 mg with each iron dose enhances absorption, particularly important in adolescents with dietary insufficiency. 1

• Alternative formulations (ferrous gluconate or ferrous fumarate) can be tried if gastrointestinal side effects occur, though ferrous sulfate remains first-line. 1

• Continue oral iron for at least 3 months after hemoglobin normalizes to replenish iron stores completely. 1

Concurrent Vitamin D Management

Treat the severe vitamin D deficiency (12 ng/mL) with cholecalciferol 50,000 IU weekly for 8 weeks, followed by maintenance dosing of 1,000–2,000 IU daily. 1 Vitamin D deficiency does not cause microcytic anemia but requires correction in adolescents for bone health.

Investigation of Underlying Cause

In Adolescent Females

• Heavy menstrual bleeding is the most common cause of iron-deficiency anemia in premenopausal women and should be assessed through menstrual history (duration, frequency, clot passage, pad/tampon changes per day). 1

• Dietary inadequacy, particularly vegetarian or vegan eating patterns, increases iron-deficiency risk in adolescents and requires nutritional assessment. 1

• Gastrointestinal blood loss must be excluded even in adolescents if menstrual history does not fully explain the severity of anemia; consider testing for H. pylori and celiac disease (tissue transglutaminase antibody with total IgA). 1

When to Pursue Endoscopy

• Upper endoscopy with duodenal biopsies and colonoscopy are indicated if the patient fails to respond to oral iron within 4 weeks despite good compliance, or if gastrointestinal symptoms (abdominal pain, diarrhea, weight loss) are present. 1

• Celiac disease accounts for 2–3% of iron-deficiency anemia cases and should be screened serologically before endoscopy. 1

Monitoring Response to Treatment

• Recheck hemoglobin and reticulocyte count at 2 weeks; an appropriate response shows hemoglobin increase ≥10 g/L and reticulocytosis. 1

• Measure hemoglobin, MCV, and ferritin at 3-month intervals for one year, then annually to ensure sustained correction and adequate iron stores. 1

• Target ferritin >30 µg/L to confirm iron store repletion before discontinuing supplementation. 1

When Oral Iron Fails

If hemoglobin does not rise ≥2 g/dL within 4 weeks despite documented compliance, consider:

• Non-compliance (most common cause of treatment failure). 1

• Ongoing blood loss exceeding replacement capacity. 1

• Malabsorption (celiac disease, H. pylori infection, autoimmune atrophic gastritis, inflammatory bowel disease). 1

• Iron-refractory iron deficiency anemia (IRIDA), a rare genetic disorder characterized by remarkably low TSAT with low-to-normal ferritin and failure to respond to oral iron but partial response to intravenous iron; this is unlikely in a typical adolescent presentation. 1

Intravenous Iron Indications

Switch to intravenous iron (iron sucrose or ferric carboxymaltose) if malabsorption is confirmed or true intolerance to all oral formulations occurs; expect hemoglobin increase ≥2 g/dL within 4 weeks. 1

Critical Pitfalls to Avoid

• Do not order hemoglobin electrophoresis as a first-line test; reserve it for cases with normal iron studies (ferritin >30 µg/L and TSAT >20%) or when MCV is disproportionately low relative to anemia severity. 1

• Do not assume dietary insufficiency alone explains severe iron-deficiency anemia in adolescents; always investigate for occult blood loss, especially if anemia is moderate-to-severe. 1

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

• Do not overlook combined nutrient deficiencies; iron deficiency can coexist with vitamin B12 or folate deficiency, recognizable by an elevated RDW with mixed red-cell populations. 1

• Do not stop iron supplementation when hemoglobin normalizes; continue for 3 additional months to replenish iron stores and prevent early relapse. 1