What is the recommended initial management and diagnostic work‑up for a young adult female with severe anemia (hemoglobin 55 g/L) and no history of abnormal menstruation?

Diagnostic Work-Up for Severe Anemia (Hemoglobin 55 g/L) in a Young Adult Female Without Menstrual Abnormalities

This young woman requires immediate investigation for gastrointestinal blood loss and malabsorption disorders, as the absence of abnormal menstruation does not exclude these critical causes of severe iron-deficiency anemia.

Immediate Laboratory Confirmation

Confirm iron deficiency with serum ferritin and transferrin saturation as the first-line diagnostic tests. 1, 2

• Serum ferritin <15 μg/L confirms absent iron stores with 99% specificity 2
• Ferritin <30 μg/L indicates low body iron stores 1, 2
• A ferritin cut-off of 45 μg/L provides optimal sensitivity and specificity in routine practice 1, 2
• Transferrin saturation <16-20% confirms iron deficiency, particularly when ferritin may be falsely elevated by inflammation 1, 2

Order C-reactive protein (CRP) concurrently because ferritin is an acute-phase reactant that can be falsely elevated in inflammatory, infectious, malignant, or hepatic conditions. 2

Measure mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV), as MCH is more reliable than MCV for detecting iron deficiency because it is less dependent on storage conditions. 1

Check red cell distribution width (RDW), as a low MCV with RDW >14% suggests iron deficiency, while RDW ≤14% suggests thalassemia minor. 2

Mandatory Gastrointestinal Investigation

All young adult women with confirmed iron-deficiency anemia require gastrointestinal evaluation (upper endoscopy with duodenal biopsies and colonoscopy) even when menstrual loss appears absent, because occult GI bleeding—particularly from malignancy or celiac disease—must be excluded. 1, 2

Upper Endoscopy with Small Bowel Biopsies

Upper endoscopy with duodenal biopsies is mandatory to exclude celiac disease, which accounts for 2-3% of iron-deficiency anemia cases. 1, 2

Upper endoscopy also identifies gastric malignancy, NSAID-induced gastropathy, peptic ulcer disease, and angiodysplasia as potential sources of occult blood loss. 1, 2

Upper endoscopy identifies an underlying cause in 30-50% of patients with iron-deficiency anemia. 2

Colonoscopy

Colonoscopy is essential to exclude colonic carcinoma, adenomatous polyps, angiodysplasia, and inflammatory bowel disease. 1, 2

A source of gastrointestinal bleeding is found in 60-70% of patients with iron-deficiency anemia who are referred for endoscopy. 3

Investigation should be considered at any level of anemia with confirmed iron deficiency, as more severe anemia correlates with higher likelihood of serious underlying GI pathology. 1, 2

Additional Diagnostic Considerations

If iron studies are normal or borderline despite severe microcytosis, order hemoglobin electrophoresis to exclude thalassemia trait, particularly if there is appropriate ethnic background or MCV disproportionately low relative to degree of anemia. 1, 2

Check vitamin B12 and folate levels, as iron deficiency may coexist with these deficiencies—an elevated RDW suggests combined deficiencies. 1, 2

Consider celiac serology (tissue transglutaminase antibodies) before endoscopy if malabsorption is suspected. 2

Immediate Treatment While Investigation Proceeds

Initiate oral iron supplementation (ferrous sulfate 200 mg three times daily) immediately while diagnostic work-up proceeds. 2

A good response to iron therapy—defined as hemoglobin rise ≥10 g/L within 2 weeks—confirms iron deficiency even if iron studies are equivocal. 1

Consider intravenous iron if malabsorption is present or rapid repletion is needed, with expected hemoglobin increase of at least 2 g/dL within 4 weeks. 4, 2, 5

Iron therapy should continue for three months after correction of anemia to replenish body stores. 1, 4, 2

Assessment for Transfusion Need

With hemoglobin 55 g/L (5.5 g/dL), assess for cardiac symptoms, hemodynamic instability, or severe symptomatic anemia to determine transfusion need. 4, 5

A restrictive transfusion strategy targeting hemoglobin 7-8 g/dL is appropriate for stable patients without cardiac disease. 4, 5

Transfusion should be reserved for patients with severe symptomatic anemia or hemodynamic instability, not based solely on hemoglobin threshold. 4

Critical Pitfalls to Avoid

Do not attribute severe iron-deficiency anemia in young adults solely to dietary insufficiency or assume menstrual loss is the cause without investigation—mandatory GI evaluation is essential. 1, 2

Do not assume all microcytic anemia is iron deficiency—anemia of chronic disease (ferritin >100 μg/L with transferrin saturation <20%), thalassemia, and sideroblastic anemia require different management. 1, 2

Do not rely on ferritin alone when inflammation is present—add transferrin saturation to confirm iron deficiency. 1, 2

Do not accept oesophagitis, erosions, or peptic ulcer as the sole cause of iron deficiency until lower GI tract has been examined, as dual pathology occurs in 10-15% of patients. 1

If the patient fails to respond to oral iron within 2-4 weeks, consider non-compliance, ongoing blood loss, malabsorption, or rare genetic disorders such as IRIDA (iron-refractory iron deficiency anemia). 2, 5