Management of Microcytic Hypochromic Anemia in a 54-Year-Old Male
Order serum ferritin and transferrin saturation immediately, as these are the most specific tests to confirm iron deficiency anemia, which is the most likely diagnosis in this patient with low MCV and low MCH. 1
Diagnostic Workup
Initial Laboratory Tests
Obtain the following tests to establish the diagnosis:
- Serum ferritin: A level <30 μg/L confirms iron deficiency in the absence of inflammation, while <15 μg/L indicates absent iron stores 1
- Transferrin saturation (TSAT): A level <16-20% supports iron deficiency and is less affected by inflammation than ferritin 1, 2
- Red cell distribution width (RDW): A low MCV with RDW >14.0% strongly suggests iron deficiency anemia, while RDW ≤14.0% suggests thalassemia minor 1
- C-reactive protein (CRP): Essential to interpret ferritin correctly, as ferritin can be falsely elevated by inflammation up to 100 μg/L despite true iron deficiency 1
- Reticulocyte count: A low count indicates impaired erythropoiesis, while elevated count suggests increased red cell production 2
Critical Interpretation Points
If ferritin is 30-100 μg/L with elevated CRP, iron deficiency may still be present—add TSAT to confirm the diagnosis. 1 A TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease rather than iron deficiency. 1
If ferritin is >100 μg/L, iron deficiency is almost certainly not present, and you should consider alternative diagnoses. 1
Treatment Algorithm
First-Line Treatment for Confirmed Iron Deficiency
Start oral ferrous sulfate 200 mg three times daily for at least three months after hemoglobin correction to replenish iron stores. 1 Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated. 1
Add ascorbic acid (vitamin C) to enhance iron absorption. 1
Expected Response and Monitoring
Hemoglobin should rise ≥10 g/L within 2 weeks if iron deficiency is the cause. 1 If this response occurs, it confirms the diagnosis of iron deficiency anemia. 1
Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year, then after a further year. 1
Management of Treatment Failure
If the patient fails to respond to oral iron within 2-4 weeks, consider the following causes:
- Non-compliance with medication 1
- Ongoing blood loss (most common in adult males) 1
- Malabsorption disorders (celiac disease, H. pylori infection, autoimmune atrophic gastritis) 1
- True intolerance to oral preparations 1
For confirmed malabsorption, switch to intravenous iron (iron sucrose or iron gluconate), which should increase hemoglobin by at least 2 g/dL within 4 weeks. 1
Investigation of Underlying Cause
Mandatory Evaluation in Adult Males
All adult men with confirmed iron deficiency require investigation for gastrointestinal blood loss, as this is the most common cause in this population. 1 This is a critical step that should never be skipped.
Perform the following investigations:
- Upper GI endoscopy with small bowel biopsies to rule out celiac disease (present in 2-3% of iron deficiency anemia patients) and other upper GI sources of bleeding 1
- Colonoscopy to rule out colonic cancer, polyps, and angiodysplasia, particularly in patients over 50 years old 1
Men with hemoglobin <110 g/L warrant fast-track GI referral. 1
Differential Diagnosis Considerations
When to Consider Alternative Diagnoses
If iron studies are normal (ferritin >30 μg/L and TSAT >20%), order hemoglobin electrophoresis to evaluate for thalassemia trait, especially if:
- MCV is disproportionately low relative to the degree of anemia 1
- RDW is normal or near normal 1
- Patient has appropriate ethnic background (Mediterranean, Asian, African descent) 1
Consider rare genetic disorders if:
- Extreme microcytosis (MCV <70 fL) is present 1
- Family history of refractory anemia exists 1
- Patient fails to respond to both oral and intravenous iron 1
Rare Genetic Causes to Consider
IRIDA (Iron-Refractory Iron Deficiency Anemia) should be suspected if there is remarkably low TSAT with low-to-normal ferritin and failure to respond to oral iron but potential response to IV iron. 1
X-linked sideroblastic anemia (ALAS2 defects) can be treated with pyridoxine (vitamin B6) 50-200 mg daily initially, then 10-100 mg daily lifelong if responsive. 1
Critical Pitfalls to Avoid
Do not 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, as it can be falsely elevated by inflammation—always add TSAT to the diagnostic workup. 1
Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency, recognizable by elevated RDW. 1
Always investigate the source of iron loss in adult males with confirmed iron deficiency, as gastrointestinal malignancy must be excluded. 1