What is the diagnosis and recommended treatment for an 81‑year‑old woman with low mean corpuscular hemoglobin concentration, low mean corpuscular hemoglobin, mildly elevated red‑cell distribution width, borderline hemoglobin A1c of 6.5%, and low HDL cholesterol?

Diagnosis: Iron Deficiency Anemia

This 81-year-old woman has iron deficiency anemia, confirmed by her microcytic hypochromic indices (low MCH 25.3, low MCHC 30.8) combined with elevated RDW 15.5, and she requires immediate oral iron supplementation while undergoing urgent gastrointestinal investigation to identify the source of blood loss. 1

Laboratory Interpretation

• The combination of low MCH (25.3) and low MCHC (30.8) with elevated RDW (15.5) is diagnostic of iron deficiency anemia, as this pattern distinguishes it from thalassemia trait, which typically presents with RDW ≤14.0%. 1, 2

• MCH is actually more reliable than MCV for detecting iron deficiency because it decreases in both absolute and functional iron deficiency and is less dependent on storage conditions. 1, 2

• The elevated RDW >14.0% combined with microcytic hypochromic indices strongly favors iron deficiency over thalassemia minor. 1

Essential Confirmatory Testing Required

Before initiating treatment, obtain the following laboratory studies immediately:

• Serum ferritin (the single most powerful test for iron deficiency): levels <30 μg/L confirm low iron stores, though a cut-off of 45 μg/L provides optimal sensitivity and specificity in practice. 1, 2

• Transferrin saturation (TSAT): values <16-20% confirm insufficient circulating iron for erythropoiesis. 1, 2

• C-reactive protein (CRP): essential because ferritin is an acute-phase reactant that can be falsely elevated by inflammation, malignancy, or hepatic disease in elderly patients. 1

• In this 81-year-old, ferritin may be falsely elevated above normal despite true iron deficiency due to chronic inflammation, malignancy, or hepatic disease; ferritin up to 100 μg/L may still indicate iron deficiency in the presence of inflammation. 1, 2

Immediate Treatment Protocol

Start oral iron supplementation immediately while diagnostic workup proceeds:

• Ferrous sulfate 200 mg three times daily is first-line treatment, to be continued for at least three months after correction of anemia to replenish iron stores. 1

• Alternative formulations (ferrous gluconate or ferrous fumarate) can be tried if ferrous sulfate is not tolerated, and ascorbic acid can be added to enhance absorption. 1

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

• Lower-dose formulations may be as effective and have lower risk of adverse effects in elderly patients. 3

Mandatory Gastrointestinal Investigation

This elderly patient requires urgent bidirectional endoscopy regardless of symptoms:

• In elderly patients with confirmed iron deficiency anemia, gastrointestinal blood loss—particularly from malignancy—is the most common cause and must be excluded. 1

• Upper endoscopy with duodenal biopsies is mandatory to exclude celiac disease (present in 2-3% of iron deficiency anemia patients), gastric malignancy, NSAID-induced gastropathy, and peptic ulcer disease. 1

• Colonoscopy is high-yield in older adults for detecting colonic carcinoma, adenomatous polyps, and angiodysplasia. 1

• Do not accept upper GI findings (such as esophagitis or erosions) as the sole cause without also examining the lower GI tract, because dual pathology is present in approximately 10-15% of patients. 1

Addressing the Comorbidities

The patient's other laboratory abnormalities require attention but are secondary priorities:

• A1c of 6.5% indicates prediabetes and requires lifestyle modification counseling, but does not explain the anemia. [@general medicine knowledge@]

• HDL of 37 mg/dL is low and increases cardiovascular risk; statin therapy and lifestyle modification should be considered after addressing the acute anemia. [@general medicine knowledge@]

• These metabolic abnormalities do not alter the iron deficiency anemia management algorithm.

Monitoring and Follow-up

• Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year, then after a further year. 1

• Expect hemoglobin increase of at least 2 g/dL within 4 weeks of starting oral iron therapy. 1

• Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up. 1

Critical Pitfalls to Avoid

• Do not attribute iron deficiency anemia in an 81-year-old solely to dietary insufficiency; mandatory GI evaluation is essential to exclude malignancy. 1

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

• Do not rely on ferritin alone in elderly patients: it can be falsely elevated by inflammation, infection, malignancy, or liver disease despite true iron deficiency. 1, 2

• Do not assume all microcytic anemia is iron deficiency: if iron studies are normal, hemoglobin electrophoresis should be ordered to exclude thalassemia trait. 1

If Oral Iron Fails

If the patient fails to respond to oral iron therapy within 2-4 weeks, consider:

• Non-compliance with medication
• Ongoing blood loss
• Malabsorption (celiac disease, H. pylori infection, autoimmune atrophic gastritis)
• Switch to intravenous iron (iron sucrose or iron gluconate) if malabsorption is confirmed, with expected hemoglobin increase of at least 2 g/dL within 4 weeks. 1, 4