What is the most likely cause and appropriate work‑up and treatment for a patient with low mean corpuscular volume, low serum iron, and low hemoglobin?

Diagnosis and Management of Low MCV, Low Iron, Low Hemoglobin

The most likely diagnosis is iron-deficiency anemia, and you should immediately order serum ferritin and transferrin saturation to confirm the diagnosis, then investigate the source of iron loss—particularly gastrointestinal bleeding—while starting oral iron supplementation concurrently. 1

Diagnostic Confirmation

Serum ferritin is the single most powerful test for diagnosing iron deficiency. 2, 1

• Ferritin <15 µg/L confirms absent iron stores with 99% specificity 1
• Ferritin <30 µg/L indicates depleted iron stores 1
• A cut-off of 45 µg/L provides optimal sensitivity and specificity in routine practice 1
• Ferritin >100 µg/L essentially excludes iron deficiency, even in inflammatory states 2, 1

Add transferrin saturation when ferritin may be falsely elevated by inflammation, malignancy, or liver disease. 2, 1

• TSAT <16–20% confirms iron deficiency 1
• Measure C-reactive protein concurrently, because ferritin is an acute-phase reactant that rises with inflammation 1
• In inflammatory states, ferritin up to 100 µg/L may still indicate iron deficiency if TSAT is low 2, 1

Use red cell distribution width (RDW) to distinguish iron deficiency from thalassemia trait:

• Low MCV + RDW >14% → iron-deficiency anemia 1
• Low MCV + RDW ≤14% → thalassemia minor 1
• Order hemoglobin electrophoresis only after iron studies are normal or borderline, or when MCV is disproportionately low relative to anemia severity 1

Investigation of the Underlying Cause

Do not treat with iron alone—you must identify the source of iron loss. 2, 1

Gastrointestinal Evaluation (Highest Priority)

All adults with confirmed iron-deficiency anemia require gastrointestinal investigation unless there is documented significant non-GI blood loss. 2, 1

• Men with hemoglobin <110 g/L warrant fast-track upper endoscopy and colonoscopy 1
• Non-menstruating women with hemoglobin <100 g/L require the same urgent evaluation 1
• Investigation should be considered at any level of anemia when iron deficiency is confirmed, because more severe anemia correlates with higher likelihood of serious GI pathology 1

Upper endoscopy with duodenal biopsies:

• Identifies a cause in 30–50% of cases 2, 1
• Duodenal biopsies are mandatory to screen for celiac disease, which accounts for 2–3% of iron-deficiency anemia 2, 1
• Also detects gastric cancer, NSAID-induced gastropathy, peptic ulcer disease, and angiodysplasia 2, 1

Colonoscopy:

• Particularly high-yield in older adults for detecting colonic carcinoma, adenomatous polyps, and angiodysplasia 2, 1
• Do not accept upper GI findings (erosions, peptic ulcer) as the sole cause without examining the lower GI tract, because dual pathology occurs in 10–15% of patients 1

Other Causes to Evaluate

• Heavy menstrual bleeding in premenopausal women 1
• Dietary inadequacy (vegetarian/vegan diets), though borderline deficient diets are common and should not preclude full GI investigation 2, 1
• Malabsorption disorders: celiac disease, H. pylori infection, autoimmune atrophic gastritis 1
• NSAID or aspirin use—document and stop whenever possible, but do not defer investigation 2

Immediate Treatment Protocol

Start oral iron supplementation immediately while diagnostic work-up proceeds. 1

• Ferrous sulfate 200–325 mg three times daily for at least three months after correction of anemia to replenish iron stores 1
• Alternative formulations (ferrous gluconate, ferrous fumarate) if ferrous sulfate is not tolerated 1
• Add ascorbic acid to enhance absorption 1

A hemoglobin rise ≥10 g/L within 2 weeks confirms iron-deficiency anemia, even when initial iron studies are equivocal. 1

When to Use Intravenous Iron

Consider IV iron if:

• Malabsorption is present 1
• Failure to respond to oral iron after 2–4 weeks despite good compliance 1
• Expected hemoglobin increase of at least 2 g/dL within 4 weeks 1
• Iron sucrose or ferric carboxymaltose are preferred formulations 1

Monitoring and Follow-Up

• Monitor hemoglobin and red cell indices at three-monthly intervals for one year, then after a further year 1
• Provide additional oral iron if hemoglobin or MCV falls below normal 1
• Check serum ferritin and transferrin saturation to assess iron stores 1

Critical Pitfalls to Avoid

Do not assume all microcytic anemia is iron deficiency—anemia of chronic disease, thalassemia, and sideroblastic anemia require different management. 1

• Anemia of chronic disease: low iron + low TIBC + ferritin >100 µg/L + TSAT <20% 1
• Thalassemia trait: normal iron studies + RDW ≤14% + elevated hemoglobin A2 on electrophoresis 1, 3

Do not rely on ferritin alone in inflammatory states—add TSAT and CRP. 1

Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency, recognizable by elevated RDW. 2, 1

Do not attribute iron-deficiency anemia in adults solely to dietary inadequacy—occult GI bleeding, especially from malignancy, must be excluded. 2, 1

Do not delay GI investigation even when heavy menstrual bleeding appears explanatory in premenopausal women. 1

Do not discontinue anticoagulants or antiplatelet agents for endoscopy unless active bleeding is present—the cardiovascular risk outweighs procedural bleeding risk. 1