What is the management approach for a patient with microcytic anemia (low MCV) and hypochromia (low hemoglobin)?

Management of Microcytic Anemia (Low MCV, Low Hemoglobin)

Begin oral iron supplementation with ferrous sulfate 200 mg three times daily immediately while simultaneously investigating the underlying cause, as iron deficiency anemia is the most common etiology and treatment should not be delayed pending complete workup. 1

Initial Diagnostic Workup

The minimum laboratory evaluation must include:

• Serum ferritin (most specific test for iron deficiency): <15 μg/L is diagnostic of iron deficiency, <30 μg/L indicates low iron stores, and <45 μg/L warrants investigation even with inflammation 1
• Transferrin saturation to assess functional iron availability 1
• Red cell distribution width (RDW): elevated RDW (>14%) with low MCV suggests iron deficiency, while normal RDW suggests thalassemia 2
• Reticulocyte count to distinguish impaired production from hemolysis 1
• C-reactive protein (CRP) to identify inflammation that may elevate ferritin falsely 1

Critical caveat: Ferritin is an acute phase reactant—levels up to 100 μg/L may still represent iron deficiency in the presence of inflammation, chronic disease, or malignancy 1

Differential Diagnosis Algorithm

If ferritin <30 μg/L (or <100 μg/L with inflammation):

• Diagnosis: Iron deficiency anemia 1
• Proceed to identify source of iron loss (see Investigation section below)

If ferritin >100 μg/L with microcytosis:

• Consider thalassemia: Order hemoglobin electrophoresis, particularly in appropriate ethnic backgrounds (Mediterranean, Asian, African descent) 1
• Consider anemia of chronic disease: Check inflammatory markers, assess for underlying chronic conditions 1
• Consider sideroblastic anemia: Rare, may require bone marrow examination 3, 4

If normal ferritin (30-100 μg/L) with microcytosis:

• Check transferrin saturation: <30% suggests functional iron deficiency 1
• Consider combined deficiencies (iron + B12/folate): elevated RDW may indicate this 1

Investigation for Source of Iron Loss

All adult men and postmenopausal women with confirmed iron deficiency anemia require bidirectional gastrointestinal evaluation to exclude malignancy. 1

Mandatory investigations:

• Upper endoscopy with duodenal biopsies to exclude celiac disease, gastric cancer, and peptic ulcer disease 1
• Colonoscopy (preferred) or barium enema to exclude colorectal cancer and polyps 1

Additional considerations:

• NSAID use history: common cause of occult GI blood loss 1
• Dietary assessment: particularly in vegetarians or those with restricted diets 1
• Menstrual history in premenopausal women: menorrhagia is the most common cause in this population 1

Important: Women over age 45 should be investigated with GI endoscopy regardless of menstrual status due to increasing cancer risk 1

Treatment Protocol

First-line therapy:

• Ferrous sulfate 200 mg orally three times daily 1, 2
• Alternative formulations if intolerant: ferrous gluconate or ferrous fumarate 1, 2
• Add ascorbic acid to enhance absorption if response is suboptimal 1, 2

Expected response:

• Hemoglobin should rise by 2 g/dL within 3-4 weeks 1, 2
• Failure to respond indicates: non-compliance, continued blood loss, malabsorption, or misdiagnosis 1

Duration:

• Continue iron for 3 months after hemoglobin normalization to replenish iron stores 1, 2

Intravenous iron indications:

• Intolerance to at least two oral formulations 1
• Documented malabsorption (e.g., celiac disease, inflammatory bowel disease) 2
• Ongoing losses exceeding oral replacement capacity 3

Warning: Parenteral iron carries risk of anaphylaxis and is more expensive; reserve for specific indications only 1

Monitoring Strategy

• Recheck hemoglobin and MCV at 3-4 weeks to confirm response 1, 2
• After correction: monitor every 3 months for 1 year, then annually 1, 2
• Restart iron supplementation if hemoglobin or MCV falls below normal 1, 2
• Further investigation warranted only if anemia becomes transfusion-dependent or visible blood loss occurs 1

Special Populations

Premenopausal women <45 years:

• May defer GI investigation if menorrhagia is clearly documented and responds to iron therapy 1
• Must investigate if: age >45, no menstrual explanation, or failure to respond to iron 1

Patients with severe comorbidity:

• Discuss appropriateness of invasive investigation if results would not change management 1

Common Pitfalls to Avoid

• Do not assume thalassemia without hemoglobin electrophoresis confirmation, even in high-risk ethnic groups 1
• Do not rely on fecal occult blood testing—it is insensitive and non-specific for iron deficiency workup 1
• Do not overlook combined deficiencies: check B12 and folate if RDW is elevated despite microcytosis 1
• Do not stop investigation at normal ferritin if inflammation is present—use 100 μg/L threshold instead 1