What is the appropriate evaluation and initial management for a 53-year-old male with mild microcytic/hypochromic anemia (hemoglobin 12.3 g/dL, MCHC 31.1 g/dL, RDW 15.6 %)?

Evaluation and Management of Mild Microcytic Anemia in a 53-Year-Old Male

This patient requires immediate iron studies (serum ferritin, transferrin saturation, and C-reactive protein) to confirm iron deficiency anemia, followed by investigation for gastrointestinal blood loss as the most likely underlying cause in an adult male. 1, 2

Laboratory Interpretation

Current findings indicate evolving iron-deficient erythropoiesis:

• The MCHC of 31.1 g/dL (normal 32–36 g/dL) confirms hypochromia, meaning red blood cells contain less hemoglobin than normal, which strongly suggests iron deficiency 1
• The elevated RDW of 15.6% combined with low MCHC indicates a mixed population of older normal-sized cells and newer microcytic, hypochromic cells—a hallmark pattern of iron deficiency anemia 1, 3, 4
• Hemoglobin 12.3 g/dL meets WHO criteria for anemia in men (< 13 g/dL), though the anemia is mild 3
• MCH is a more reliable marker than MCHC for detecting iron deficiency because it is less affected by specimen storage and laboratory equipment 1, 2

Diagnostic Workup Algorithm

First-Line Tests (Order Immediately)

1. Serum ferritin – the single most specific test for iron deficiency 1, 2

   • < 15 μg/L confirms absent iron stores with 99% specificity 1, 2
   • < 30 μg/L indicates depleted iron stores 1, 2
   • 45 μg/L provides optimal sensitivity and specificity in practice 2

2. Transferrin saturation (TSAT) – less affected by inflammation than ferritin 1, 3

   • < 16–20% confirms iron deficiency 1, 3, 2
   • Use this threshold when ferritin may be falsely elevated 1

3. C-reactive protein (CRP) – essential for interpreting ferritin 1, 3

   • Ferritin is an acute-phase reactant and rises with inflammation, infection, malignancy, or liver disease 1, 2
   • In inflammatory states, ferritin up to 100 μg/L may still indicate iron deficiency 1, 2

4. Absolute reticulocyte count – evaluates bone marrow response 5, 3

   • Low or normal count indicates inadequate marrow response to anemia 1, 3

If Iron Studies Confirm Deficiency

Adult males with confirmed iron deficiency require investigation for gastrointestinal blood loss, as dietary insufficiency alone is extremely rare in this population 1, 2:

• Upper endoscopy with duodenal biopsies to exclude:

  • Celiac disease (present in 2–3% of iron deficiency cases) 1, 2
  • Gastric cancer, peptic ulcer disease, NSAID gastropathy 1, 2

• Colonoscopy to detect:

  • Colonic carcinoma, adenomatous polyps, angiodysplasia 1, 2

• Fast-track GI referral is recommended for men with hemoglobin < 110 g/L (11 g/dL), though investigation should be considered at any anemia level when iron deficiency is confirmed 2

If Iron Studies Are Normal

Order hemoglobin electrophoresis to evaluate for thalassemia trait 1, 3, 2:

• Thalassemia typically shows MCV disproportionately low relative to anemia severity 1, 2
• RDW ≤ 14% favors thalassemia over iron deficiency 1, 2, 4
• Normal iron parameters (ferritin > 30 μg/L, TSAT > 20%) with persistent microcytosis suggest thalassemia 1, 2

Initial Treatment

Begin oral iron supplementation immediately while diagnostic workup proceeds 1, 2:

• Ferrous sulfate 325 mg (65 mg elemental iron) once to three times daily 1
• Take between meals to maximize absorption 1
• A hemoglobin rise ≥ 10 g/L (≈ 1 g/dL) within 2 weeks confirms iron deficiency even when baseline iron studies are equivocal 1, 2
• Continue supplementation for 3–6 months after hemoglobin normalizes to replenish iron stores 1

Critical Pitfalls to Avoid

• Do not attribute iron deficiency in adult males to dietary insufficiency without excluding GI blood loss—occult bleeding from malignancy is the primary concern 1, 2
• Do not rely on ferritin alone when inflammation is present—add TSAT and CRP to avoid false-negative results 1, 2
• Do not order hemoglobin electrophoresis as a first-line test—it is only indicated when iron studies are normal or borderline 1, 2
• Do not overlook combined deficiencies—iron deficiency can coexist with vitamin B12 or folate deficiency, suggested by elevated RDW 1, 2
• Do not assume MCV alone is sufficient—early iron deficiency may present with normal MCV while MCH and MCHC are already reduced 1, 6

Expected Response and Monitoring

• Hemoglobin should increase by at least 2 g/dL within 4 weeks of oral iron therapy 2
• If no response occurs, reassess adherence, evaluate for ongoing blood loss or malabsorption, and consider alternative diagnoses such as thalassemia trait or anemia of chronic disease 3, 2
• Monitor hemoglobin and iron studies at 4–8 weeks, then at 3-month intervals for one year 2