What is the most likely diagnosis and recommended work‑up and treatment for a patient with hemoglobin 9.5 g/dL, hematocrit 31.8 %, mean corpuscular volume 78.1 fL, mean corpuscular hemoglobin 23.3 pg, mean corpuscular hemoglobin concentration 29.9 g/dL, and red‑cell distribution width 15.8 %?

Microcytic Hypochromic Iron Deficiency Anemia

This patient has moderate iron deficiency anemia (IDA) requiring immediate oral iron supplementation and urgent bidirectional endoscopy to exclude gastrointestinal malignancy.

Diagnosis

The laboratory pattern is diagnostic for iron deficiency anemia without requiring additional testing 1:

• Hemoglobin 9.5 g/dL confirms moderate anemia by WHO criteria (< 12 g/dL for non-pregnant women) 2
• MCV 78.1 fL demonstrates microcytosis characteristic of iron deficiency 2
• MCH 23.3 pg and MCHC 29.9 g/dL confirm hypochromia, the hallmark of insufficient iron for hemoglobin synthesis 1
• RDW 15.8% (elevated above 14%) is an early and sensitive marker of iron deficiency, reflecting anisocytosis from mixed populations of microcytic and normocytic cells 1, 3

This constellation has 82.3% sensitivity and 97.4% specificity for iron deficiency 3.

Essential Confirmatory Testing

Order the following iron studies immediately 1, 4:

• Serum ferritin – expect < 30 µg/L (likely < 15 µg/L given severity)
• Transferrin saturation (TSAT) – calculated as (serum iron × 100) ÷ TIBC; expect < 20%
• C-reactive protein (CRP) – to detect inflammation that may falsely elevate ferritin

Critical interpretation: Ferritin < 15 µg/L has 99% specificity for absolute iron deficiency 1, 4. TSAT < 20% is the decisive confirmatory marker 1, 4. If CRP is elevated and ferritin falls between 30–100 µg/L, this still represents true iron deficiency requiring treatment 1, 4.

Mandatory Gastrointestinal Investigation

Bidirectional endoscopy (upper endoscopy plus colonoscopy) must be performed urgently 2, 1:

• In adults with IDA, gastrointestinal bleeding is presumptive until proven otherwise; occult malignancy must be excluded 1
• Colorectal and gastric cancers are the most common serious causes in this demographic 2, 1
• Investigation should not be delayed even though hemoglobin is above fast-track thresholds; any degree of anemia with iron deficiency warrants full evaluation 2, 1
• During upper endoscopy, obtain small bowel biopsies because 2–3% of IDA patients have celiac disease 4

Common pitfall: Do not attribute iron deficiency solely to menstrual blood loss in perimenopausal women; gastrointestinal pathology must still be investigated 1.

Immediate Treatment

Iron Replacement

Start oral elemental iron 100–200 mg daily immediately while diagnostic workup proceeds 1:

• Continue for at least 3–6 months after hemoglobin normalizes to fully replenish stores (target ferritin > 50 µg/L) 1
• Do not discontinue when hemoglobin normalizes; iron stores must be restored to prevent rapid recurrence 1
• Switch to intravenous iron if oral iron is poorly tolerated, malabsorption is documented, or hemoglobin fails to improve despite adherence 1

Response Monitoring

• Recheck CBC in 2–4 weeks; expect reticulocytosis within 7–10 days and hemoglobin rise of 1–2 g/dL by 3 weeks 4
• Therapeutic response to 3 weeks of oral iron confirms diagnosis when other tests are equivocal 2

Differential Diagnosis Considerations

Thalassemia Trait

If microcytosis persists after iron repletion—or if the patient belongs to an at-risk ethnic group (Mediterranean, Southeast Asian, African)—order hemoglobin electrophoresis 1:

• Thalassemia typically shows MCV reduced out of proportion to anemia severity 2
• RDW ≤ 14% with microcytosis suggests thalassemia minor, whereas RDW > 14% favors iron deficiency 1
• Do not diagnose thalassemia without first correcting iron deficiency, as the two can coexist 1

Anemia of Chronic Disease

This is effectively ruled out by the expected low ferritin 1:

• Anemia of chronic disease presents with ferritin > 100 µg/L, low TIBC, and TSAT < 20% 1
• If ferritin is 30–100 µg/L with elevated CRP, suspect combined iron deficiency and anemia of chronic disease 1, 4

Additional Workup

Complete the evaluation with 4:

• Vitamin B12 and folate levels – to exclude combined deficiencies that may mask MCV changes 1, 4
• Serum creatinine and eGFR – to assess chronic kidney disease as a contributor 4
• Reticulocyte count – low/normal confirms inadequate marrow response from deficiency; elevated suggests hemolysis 4

Common pitfall: Normal hemoglobin, hematocrit, and MCV on routine CBC can miss iron depletion; individuals with normal cell counts but low serum iron and ferritin are susceptible to developing frank anemia 5.

Key Clinical Caveats

• Mild anemia is not less indicative of serious underlying disease; no evidence supports downgrading its clinical significance 2
• Ferritin is an acute-phase reactant and can be falsely normal or elevated during inflammation, infection, malignancy, or liver disease despite true iron deficiency 2, 1
• MCH is 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 1
• In severe IDA (hemoglobin < 9 g/dL), gastrointestinal cancer and diffuse angiodysplasias are the most common causes of the lowest hemoglobin values 6