What is the best approach to diagnose and manage anemia in an elderly male patient with microcytic anemia, increased Red Cell Distribution Width (RDW), and low Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC), with a normal Hemoglobin (Hb) level and an increased Red Blood Cell (RBC) count?

Diagnostic Approach to Microcytic Anemia with Normal Hemoglobin and Elevated RBC Count

This presentation with normal hemoglobin, elevated RBC count, low MCV/MCH/MCHC, and increased RDW most likely represents early iron deficiency anemia or thalassemia trait, and you must immediately check serum ferritin and consider hemoglobin electrophoresis to differentiate these conditions. 1

Initial Diagnostic Algorithm

The combination of low MCV with RDW >14.0% strongly suggests iron deficiency anemia, while low MCV with RDW ≤14.0% points toward thalassemia minor. 1, 2 However, this RDW distinction has significant limitations—nearly half of thalassemia cases also show elevated RDW, so sequential iron studies remain essential. 3

First-Line Testing

• Serum ferritin is the single most powerful test for iron deficiency, with a cut-off of 45 μg/L providing optimal sensitivity and specificity in practice. 1, 2
• Ferritin <15 μg/L indicates absent iron stores, while <30 μg/L indicates low body iron stores. 1, 2
• If ferritin is >100 μg/L, iron deficiency is almost certainly not present. 4

Critical Caveat for Elderly Patients

In elderly males with chronic inflammation, malignancy, or hepatic disease, ferritin may be falsely elevated above 12-15 μg/L despite true iron deficiency. 4 Add transferrin saturation (TSAT) if ferritin appears falsely normal due to inflammation—TSAT <16-20% confirms iron deficiency, while TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease. 1

Differential Diagnosis Based on Laboratory Pattern

If Iron Studies Confirm Iron Deficiency

In elderly males, gastrointestinal blood loss is the most common cause and must be investigated. 4, 2 The British Society of Gastroenterology recommends fast-track GI referral for men with Hb <110 g/L. 1

Key investigations include:

• Upper GI endoscopy with small bowel biopsies (2-3% of IDA patients have celiac disease). 4
• Colonoscopy (particularly productive in elderly patients—colonic cancer, polyps, angiodysplasia). 4
• Document NSAID/aspirin use and stop if possible. 4
• Consider less common causes: gastric cancer, Crohn's disease, angiodysplasia. 4

If Iron Studies Are Normal or Elevated

Order hemoglobin electrophoresis if microcytosis persists with normal iron studies, especially with appropriate ethnic background or MCV disproportionately low relative to anemia degree. 1 Thalassemia typically presents with elevated RBC count and microcytosis, which fits this patient's presentation. 4

If Patient Fails to Respond to Iron Therapy

Consider these rare but important causes:

• IRIDA (iron-refractory iron deficiency anemia): Remarkably low TSAT with low-to-normal ferritin, fails oral iron but may respond to IV iron. 1
• X-linked sideroblastic anemia (ALAS2 defects): Trial of pyridoxine 50-200 mg daily initially, then 10-100 mg daily lifelong if responsive. 1
• Malabsorption disorders: Celiac disease, H. pylori infection, autoimmune atrophic gastritis. 1

Treatment Algorithm (If Iron Deficiency Confirmed)

• First-line: Ferrous sulfate 200 mg three times daily for at least three months after correction of anemia to replenish iron stores. 1, 2
• Alternative formulations: ferrous gluconate or ferrous fumarate if not tolerated. 1, 2
• Add ascorbic acid to enhance absorption. 1, 2
• Expected response: Hemoglobin rise ≥10 g/L within 2 weeks confirms iron deficiency. 1, 2

For Treatment Failure

Consider IV iron if malabsorption present—expect hemoglobin increase of at least 2 g/dL within 4 weeks. 1, 2

Monitoring Protocol

• Monitor hemoglobin and red cell indices at three-monthly intervals for one year, then after a further year. 1, 2
• Provide additional oral iron if hemoglobin or MCV falls below normal. 1, 2

Critical Pitfalls to Avoid

• Never assume all microcytic anemia is iron deficiency—anemia of chronic disease, thalassemia, and sideroblastic anemia require different management. 1
• Do not use ferritin alone in inflammatory states—it can be falsely elevated by inflammation. 1
• Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency, recognizable by elevated RDW. 4, 2
• In elderly males with confirmed iron deficiency, always investigate for GI blood loss—do not attribute it to diet alone. 4, 1