What is the appropriate management for a patient with microcytic, hypochromic anemia (low Hemoglobin (Hgb), Hematocrit (Hct), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC)) with a high Red Cell Distribution Width (RDW)?

Management of Microcytic, Hypochromic Anemia with Elevated RDW

This presentation is highly suggestive of iron deficiency anemia and requires immediate confirmation with serum ferritin, followed by investigation for the source of iron loss and initiation of iron replacement therapy. 1, 2

Diagnostic Confirmation

The combination of low MCV with elevated RDW (>14.0%) strongly distinguishes iron deficiency anemia from thalassemia minor, which typically presents with low MCV but normal or low RDW (≤14.0%). 1, 2 This elevated RDW reflects the heterogeneous red cell population characteristic of iron deficiency, where newer cells are progressively more microcytic as iron stores deplete. 1

Serum ferritin is the single most powerful diagnostic test and should be ordered immediately: 1, 2

• Ferritin <15 μg/L is diagnostic of iron deficiency (specificity 0.99) 1
• Ferritin <30 μg/L indicates low body iron stores 1
• Ferritin <45 μg/L warrants investigation, especially with chronic inflammation (optimal sensitivity/specificity trade-off) 1, 2
• Ferritin >100-150 μg/L essentially excludes absolute iron deficiency, even with inflammation 1

Important caveat: Ferritin is an acute phase reactant and can be falsely elevated in inflammation, malignancy, or hepatic disease. 1 In these situations, add transferrin saturation (<30% suggests iron deficiency) or consider the sTfR/ferritin ratio if available. 1, 3

Investigation for Source of Iron Loss

GI investigation should be considered in all adults with confirmed iron deficiency anemia unless there is clear non-GI blood loss. 1 The British Society of Gastroenterology recommends fast-track referral for men with Hb <110 g/L or non-menstruating women with Hb <100 g/L, though investigation should be considered at any level of anemia with confirmed iron deficiency. 1, 2

Upper GI endoscopy should be performed first in most cases: 1

• Reveals a cause in 30-50% of patients 1
• Obtain small bowel biopsies during endoscopy to screen for celiac disease (present in 2-3% of IDA patients) 1

Colonoscopy should follow, particularly prioritized in elderly patients where colonic pathology is more likely. 1

Key historical elements to document: 1

• NSAID/aspirin use (stop if possible)
• Dietary history (though borderline deficient diets are common and should not preclude full GI investigation)
• Family history of thalassemia, sideroblastic anemia, or bleeding disorders
• Ethnic background (consider hemoglobinopathy screening)

Treatment Protocol

Initiate oral iron supplementation with ferrous sulfate 200 mg three times daily: 2

• Continue for at least 3 months after anemia correction to replenish iron stores 2
• Alternative formulations (ferrous gluconate, ferrous fumarate) if ferrous sulfate not tolerated 2
• Adding ascorbic acid enhances absorption 2

Expected response confirming iron deficiency: 2

• Hemoglobin rise ≥10 g/L within 2 weeks 2
• Hemoglobin increase ≥2 g/dL within 4 weeks 2

If no response to oral iron after 3 weeks, consider: 1, 2

• Intravenous iron if malabsorption present (expected Hb increase ≥2 g/dL within 4 weeks) 2
• Evaluation for genetic disorders of iron metabolism (IRIDA, SLC11A2 defects) 2
• Hemoglobin electrophoresis if microcytosis with normal iron studies or appropriate ethnic background 1, 2
• Pyridoxine (vitamin B6) 50-200 mg daily if sideroblastic anemia suspected (ALAS2 defects) 2

Monitoring Strategy

Follow hemoglobin and red cell indices: 2

• At 3-monthly intervals for one year
• Then after a further year
• Provide additional oral iron if Hb or MCV falls below normal 2

Monitor for iron overload in patients receiving: 2

• Multiple transfusions
• Long-term iron therapy
• Consider liver MRI in specific cases to detect toxic iron loading early 2

Critical Pitfalls to Avoid

Do not assume dietary deficiency explains the anemia - full GI investigation is still required even with poor dietary intake. 1

Do not overlook combined deficiencies - the elevated RDW may indicate coexisting folate or B12 deficiency masking microcytosis. 1

Do not miss thalassemia trait - if MCV is disproportionately low relative to degree of anemia, RBC count is elevated, or iron studies are normal, order hemoglobin electrophoresis. 1

Do not stop investigation prematurely - even mild anemia warrants investigation, as severity does not correlate with likelihood of serious pathology (including colorectal cancer). 1