In a 40‑year‑old woman with hemoglobin 10.5 g/dL, hematocrit 34.1 %, mean corpuscular volume 72.1 fL, mean corpuscular hemoglobin 22.2 pg, mean corpuscular hemoglobin concentration 30.8 g/dL, and red cell distribution width 17.2 %, what is the most likely diagnosis and the appropriate initial work‑up and treatment?

Microcytic Hypochromic Iron Deficiency Anemia

This 40-year-old woman has iron deficiency anemia (IDA) and requires immediate oral iron supplementation while simultaneously investigating the underlying source of iron loss, which in premenopausal women is most commonly heavy menstrual bleeding or gastrointestinal blood loss. 1

Diagnostic Confirmation

The laboratory values definitively establish microcytic hypochromic anemia with marked anisocytosis:

• MCV 72.1 fL (microcytic) combined with elevated RDW 17.2% strongly indicates iron deficiency anemia rather than thalassemia trait, as thalassemia typically presents with RDW ≤14.0% 1, 2
• MCH 22.2 pg and MCHC 30.8 g/dL are both significantly reduced, confirming hypochromia that is characteristic of advanced iron deficiency 1, 3
• The hemoglobin 10.5 g/dL represents moderate anemia in a woman (anemia defined as <12 g/dL) 4

MCH is actually more reliable than MCV for detecting iron deficiency because it is less dependent on storage conditions and decreases in both absolute and functional iron deficiency. 3 The combination of low MCH, low MCHC, and elevated RDW >14% makes iron deficiency the overwhelming diagnostic probability. 1, 5

Required Initial Laboratory Work-Up

Order serum ferritin immediately—it is the single most powerful test for confirming iron deficiency. 1, 3, 2

• Ferritin <30 μg/L confirms iron deficiency 1, 3
• A cut-off of 45 μg/L provides optimal sensitivity and specificity in practice 1
• If ferritin appears falsely normal (30-100 μg/L), add transferrin saturation (TSAT), as ferritin is an acute-phase reactant that can be elevated by inflammation, infection, malignancy, or liver disease despite true iron deficiency 1, 3
• TSAT <16-20% confirms insufficient circulating iron for erythropoiesis 1, 3

Do not order hemoglobin electrophoresis at this stage—the elevated RDW essentially excludes thalassemia trait, which would show normal or low-normal RDW. 1, 2 Hemoglobin electrophoresis is only indicated if iron studies are normal with persistent microcytosis. 1

Immediate Treatment

Start oral ferrous sulfate 200 mg three times daily immediately while the diagnostic work-up proceeds. 1

• Alternative formulations (ferrous gluconate or ferrous fumarate) can be used if ferrous sulfate is not tolerated 1
• Adding ascorbic acid enhances iron absorption 1
• Expect hemoglobin to rise ≥10 g/L (≥1 g/dL) within 2 weeks if iron deficiency is the cause—this therapeutic response confirms the diagnosis 1
• Continue iron for at least 3 months after hemoglobin normalizes to replenish iron stores 1

Mandatory Investigation of Underlying Cause

In a 40-year-old woman, iron deficiency anemia requires investigation for both menstrual and gastrointestinal blood loss—these are the two most common etiologies. 1

Menstrual History

• Quantify menstrual blood loss: duration of menses, number of pads/tampons per day, presence of clots 1
• Heavy menstrual bleeding is the most common cause in premenopausal women 1

Gastrointestinal Evaluation

Even if menstrual losses appear adequate to explain the anemia, gastrointestinal evaluation is still required unless menstrual loss fully accounts for the severity of anemia. 1

• Upper endoscopy with duodenal biopsies to exclude celiac disease (present in 2-3% of IDA patients), gastric malignancy, NSAID-induced gastropathy, and peptic ulcer disease 1
• Colonoscopy to exclude colonic carcinoma, polyps, angiodysplasia, and inflammatory bowel disease 1

Dietary and Medication History

• Assess dietary iron intake (red meat, fortified cereals) 1
• Document NSAID use, aspirin, or anticoagulants that increase GI bleeding risk 1

Critical Pitfalls to Avoid

• Do not attribute iron deficiency in adults solely to dietary inadequacy—occult gastrointestinal blood loss, especially from malignancy, must be excluded 1
• Do not assume all microcytic anemia is iron deficiency—anemia of chronic disease can present with microcytosis, but typically has ferritin >100 μg/L with TSAT <20% 4, 3
• Do not rely on ferritin alone if inflammation is suspected—add TSAT to avoid missing iron deficiency masked by elevated ferritin 1, 3
• Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency, suggested by elevated RDW 1, 3
• Do not delay GI investigation even when heavy menstrual bleeding appears explanatory—both sources can coexist 1

Monitoring and Follow-Up

• Recheck hemoglobin and MCV at 2-4 weeks to confirm response to oral iron 1
• If no response after 2-4 weeks, consider non-compliance, ongoing blood loss, malabsorption (celiac disease, H. pylori, atrophic gastritis), or rare genetic disorders like IRIDA 1
• For malabsorption or intolerance to oral iron, switch to intravenous iron (iron sucrose or iron gluconate) with expected hemoglobin increase ≥2 g/dL within 4 weeks 1
• Monitor hemoglobin and red cell indices at 3-month intervals for one year, then annually 1