What is the diagnosis and appropriate management for a woman with serum iron 45 µg/dL, microcytic hypochromic anemia, elevated red blood cell count, and vitamin D deficiency?

Diagnosis: Iron Deficiency Anemia with Vitamin D Deficiency

This patient has iron deficiency anemia confirmed by serum iron 45 µg/dL, microcytic hypochromic red cells, and elevated RBC count, requiring immediate oral iron supplementation while investigating the underlying cause of iron loss. 1

Diagnostic Confirmation

Iron Studies Interpretation

• Serum iron of 45 µg/dL is low and, when combined with microcytic hypochromic anemia, strongly indicates iron deficiency even before calculating transferrin saturation. 1
• A ferritin cut-off of 45 µg/L provides optimal sensitivity and specificity for diagnosing iron deficiency in clinical practice; values below this threshold confirm depleted iron stores. 1, 2
• Calculate transferrin saturation (TSAT) as (serum iron × 100) ÷ TIBC; a TSAT < 20% confirms iron deficiency that warrants treatment. 1
• Measure C-reactive protein (CRP) concurrently because ferritin is an acute-phase reactant that can be falsely elevated by inflammation, infection, or malignancy. 1

Red Cell Indices

• Microcytic hypochromic anemia is the classic laboratory signature of iron-deficient erythropoiesis and typically appears before hemoglobin falls significantly. 2
• An elevated red blood cell count in the setting of microcytic anemia reflects the bone marrow's attempt to compensate for reduced oxygen-carrying capacity per cell. 3
• Red cell distribution width (RDW) > 14% combined with low MCV strongly indicates iron deficiency rather than thalassemia trait, which usually shows RDW ≤ 14%. 1, 2

Immediate Management

Iron Replacement Therapy

• Begin oral iron supplementation with ferrous sulfate 200 mg three times daily immediately while the diagnostic work-up proceeds. 2
• A hemoglobin rise of ≥10 g/L within 2 weeks confirms iron deficiency even when initial iron studies are equivocal. 2
• Continue iron therapy for at least 3–6 months after hemoglobin normalization to fully replenish iron stores, targeting ferritin > 50 µg/L. 1
• Alternative oral formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated, and ascorbic acid can be added to enhance absorption. 2

Vitamin D Deficiency Treatment

• Treat concurrent vitamin D deficiency with cholecalciferol 50,000 IU weekly for 8 weeks, followed by maintenance dosing. 2

Investigation of Underlying Cause

Mandatory Evaluation in Women

• In adult women, the two most common etiologies are heavy menstrual bleeding and gastrointestinal bleeding; both must be evaluated systematically. 1
• All adult women with confirmed iron deficiency require gastrointestinal evaluation (upper endoscopy and colonoscopy) unless menstrual loss fully accounts for the anemia. 1
• Do not attribute iron deficiency in adult women solely to menstrual blood loss; gastrointestinal pathology must still be investigated. 1

Gastrointestinal Evaluation

• Upper endoscopy with duodenal biopsies should be performed to exclude celiac disease (present in 2–3% of iron deficiency cases), gastric malignancy, NSAID-induced gastropathy, and peptic ulcer disease. 1
• Colonoscopy is essential to exclude colonic carcinoma, adenomatous polyps, angiodysplasia, and inflammatory bowel disease. 1
• Investigation should proceed at any level of anemia when iron deficiency is confirmed, as more severe anemia correlates with higher likelihood of serious underlying pathology. 1

Malabsorption Screening

• Screen for celiac disease with serologic testing before endoscopic evaluation, as it accounts for 3–5% of iron deficiency cases. 1
• Consider H. pylori testing and evaluation for autoimmune atrophic gastritis if there is treatment failure or malabsorption is suspected. 2

Differential Diagnosis Considerations

Excluding Other Causes of Microcytosis

• If microcytosis persists after iron repletion—or if the patient belongs to an at-risk ethnic group—order hemoglobin electrophoresis to exclude β-thalassemia trait. 1
• Do not order hemoglobin electrophoresis as a first-line test; it should be reserved for cases with normal or borderline iron parameters. 1
• Anemia of chronic disease typically presents with ferritin > 100 µg/L, low TIBC, and TSAT < 20%; low ferritin effectively rules this out. 1

Rare Genetic Disorders

• Consider iron-refractory iron deficiency anemia (IRIDA) if there is remarkably low TSAT with low-to-normal ferritin and failure to respond to oral iron. 1, 2
• Before pursuing genetic testing, exclude autoimmune atrophic gastritis, H. pylori infection, and celiac disease, which can also cause oral-iron refractoriness. 1

Monitoring and Follow-Up

• Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year, then after a further year. 2
• Check serum ferritin and transferrin saturation to assess iron stores after hemoglobin normalization. 2
• Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up. 2

Critical Pitfalls to Avoid

• Do not discontinue iron supplementation once hemoglobin normalizes; iron stores must be restored (target ferritin > 50 µg/L) to prevent rapid recurrence. 1
• Do not postpone endoscopic investigation while awaiting response to iron therapy; malignancy work-up should proceed in parallel. 1
• Do not rely on serum iron alone; it shows considerable day-to-day variability and must be interpreted with TSAT and ferritin. 1
• Do not overlook combined deficiencies; iron deficiency can coexist with vitamin B12 or folate deficiency, recognizable by elevated RDW. 1

Intravenous Iron Indications

• Consider intravenous iron if oral iron is poorly tolerated, malabsorption is documented, or hemoglobin fails to improve despite adherence. 1, 2
• Expected hemoglobin increase is at least 2 g/dL within 4 weeks of IV iron administration. 2, 4