In an 80‑year‑old woman with mean corpuscular hemoglobin 25.3 pg, mean corpuscular hemoglobin concentration 30.8 g/dL, red cell distribution width 15.5 %, and hemoglobin A1c 6.5 %, what is the most likely diagnosis and appropriate treatment?

Diagnosis: Iron Deficiency Anemia

This 80-year-old woman has iron deficiency anemia, confirmed by low MCH (25.3 pg), low MCHC (30.8 g/dL), and elevated RDW (15.5%), and requires immediate oral iron supplementation plus urgent gastrointestinal investigation to identify the bleeding source. 1, 2

Laboratory Interpretation

The combination of low MCH with elevated RDW is highly specific for iron deficiency anemia, even before frank anemia develops, with a sensitivity of 72% for detecting iron deficiency. 1 MCH is more reliable than MCV for diagnosing iron deficiency because it is less dependent on storage conditions and laboratory equipment, and decreases in both absolute and functional iron deficiency. 1, 3

• Low MCHC (30.8 g/dL) indicates hypochromia, meaning red blood cells contain less hemoglobin than normal, which strongly suggests iron deficiency anemia. 1
• Elevated RDW (15.5%) reflects anisocytosis—the coexistence of normal-sized older red cells and smaller, hypochromic newer cells—which is characteristic of evolving iron deficiency. 1, 4
• The HbA1c of 6.5% may be falsely elevated by iron deficiency anemia; HbA1c decreases significantly (approximately 0.4%) following iron treatment as hemoglobin rises. 5

Required Diagnostic Workup

Order a complete iron panel immediately: 1, 3, 2

• Serum ferritin (most specific test; <30 μg/L confirms iron deficiency without inflammation; <45 μg/L provides optimal sensitivity/specificity in practice) 1, 2
• Transferrin saturation (<16–20% confirms iron deficiency; essential if ferritin is falsely elevated by inflammation) 1, 3, 2
• C-reactive protein (to assess for inflammation that can falsely elevate ferritin) 1, 3
• Complete blood count with reticulocyte count (low/normal reticulocyte count indicates impaired erythropoiesis) 1, 3

In patients with inflammation, ferritin up to 100 μg/L may still indicate iron deficiency, so transferrin saturation <20% is required to confirm the diagnosis. 6, 1

Immediate Treatment

Initiate oral iron supplementation with ferrous sulfate 325 mg (65 mg elemental iron) 1–3 times daily between meals immediately, even before completing the diagnostic workup. 1, 2

• Expect hemoglobin to increase by approximately 1–2 g/dL every 2–4 weeks. 1
• A rise in hemoglobin of ≥10 g/L (≈1 g/dL) within 2 weeks confirms iron deficiency even if iron studies are equivocal. 1, 2
• Continue iron supplementation for 3–6 months after hemoglobin normalizes to replenish iron stores. 1
• Check hemoglobin, reticulocytes, and iron studies after 4–8 weeks of therapy. 1

Mandatory Investigation for Bleeding Source

All adult women with confirmed iron deficiency anemia require gastrointestinal evaluation (upper endoscopy and colonoscopy) to exclude malignancy, even when menstrual loss appears explanatory. 2

In an 80-year-old woman, gastrointestinal blood loss—particularly from malignancy—is the most common cause of iron deficiency anemia and must be investigated urgently. 2

Upper Endoscopy with Duodenal Biopsies

• Upper endoscopy identifies an underlying cause in 30–50% of elderly patients with iron deficiency anemia. 2
• Duodenal biopsies are mandatory to screen for celiac disease, which accounts for 2–3% of iron deficiency anemia cases. 2
• Also evaluates for gastric cancer, NSAID-induced gastropathy, peptic ulcer disease, and angiodysplasia. 2

Colonoscopy

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

Alternative Diagnoses to Exclude

If iron studies are normal despite low MCH/MCHC, obtain hemoglobin electrophoresis to evaluate for thalassemia trait, especially in individuals of Mediterranean, African, or Southeast Asian descent. 1, 3

• In thalassemia trait, MCV is typically reduced disproportionately to the degree of anemia, and RDW is usually ≤14%. 1, 2
• The combination of low MCV with elevated RDW (>14%) favors iron deficiency over thalassemia. 2, 4

If ferritin is 30–100 μg/L with inflammation, consider a combination of true iron deficiency and anemia of chronic disease. 6, 1

Critical Pitfalls to Avoid

• Do not attribute iron deficiency anemia in an 80-year-old solely to dietary insufficiency; mandatory GI evaluation is essential to exclude malignancy. 2
• Do not rely on ferritin alone in elderly patients with chronic inflammation, malignancy, or hepatic disease, as ferritin may be falsely elevated; use transferrin saturation <16–20% to confirm iron deficiency. 1, 2
• Do not overlook combined deficiencies—iron deficiency can coexist with vitamin B12 or folate deficiency, recognizable by elevated RDW. 2
• Do not dismiss the HbA1c of 6.5% as definitive for diabetes diagnosis until after iron deficiency is corrected, as iron deficiency anemia falsely elevates HbA1c by approximately 0.4%. 5
• Consider parenteral iron if the patient is intolerant to oral iron, has poor response to oral iron, or has severe anemia requiring rapid correction. 1