What is the best course of treatment for a patient with microcytic anemia, indicated by a low Mean Corpuscular Volume (MCV) and high Red Cell Distribution Width (RDW), and potentially complicated by underlying chronic diseases?

Microcytic Anemia with High RDW: Diagnostic and Treatment Approach

Iron deficiency anemia is the most likely diagnosis and requires immediate serum ferritin testing followed by comprehensive gastrointestinal evaluation to identify the source of blood loss, with concurrent initiation of oral iron supplementation once iron deficiency is confirmed. 1, 2

Diagnostic Significance of Laboratory Pattern

The combination of low MCV with elevated RDW is highly specific for iron deficiency anemia rather than other causes of microcytosis:

• An RDW >14-16.9% strongly distinguishes iron deficiency from thalassemia trait, which typically presents with normal or only slightly elevated RDW 1, 3
• High RDW reflects heterogeneous red cell populations as iron stores become progressively depleted, often appearing before MCV changes become apparent 3, 2
• This pattern creates a distinctive signature that differentiates iron deficiency from anemia of chronic disease and thalassemia 1, 3

Immediate Diagnostic Workup

Serum ferritin is the single most powerful test and must be obtained immediately to confirm iron deficiency 1, 2:

• Ferritin <30 μg/L confirms iron deficiency in the absence of inflammation 1, 2
• Ferritin <100 μg/L may still indicate iron deficiency if inflammation is present 1, 2
• Measure transferrin saturation and CRP simultaneously with ferritin to assess for functional iron deficiency and interpret ferritin correctly in the context of inflammation 1, 2

Additional Essential Tests

• Transferrin saturation <30% supports iron deficiency diagnosis 2
• CRP is mandatory because inflammation elevates ferritin and can mask true iron deficiency 2
• Reticulocyte count assesses bone marrow response 3, 2

Critical Pitfall to Avoid

Serum ferritin can be falsely elevated in inflammatory conditions, chronic disease, malignancy, or liver disease, potentially masking iron deficiency 3. This is why CRP must be measured concurrently 2.

Mandatory Gastrointestinal Investigation

All adult men and post-menopausal women with confirmed iron deficiency require complete gastrointestinal evaluation, regardless of symptom presence 2:

• Upper endoscopy with mandatory small bowel biopsies (2-3% of patients have celiac disease) 2
• Colonoscopy or CT colonography to evaluate for malignancy 2
• This presentation warrants investigation for malignancy, as gastrointestinal blood loss is the most common source in these populations 2

Do Not Assume Dietary Deficiency

Never assume dietary deficiency alone without complete GI evaluation, as this can delay diagnosis of malignancy 2.

Treatment Algorithm

Step 1: Confirm Iron Deficiency with Ferritin

• If ferritin confirms iron deficiency (<30 μg/L), proceed to Step 2 1, 2
• If ferritin is normal (>100 μg/L) despite high RDW, proceed to hemoglobin electrophoresis to exclude thalassemia trait, though this is unlikely given the elevated RDW 1

Step 2: Initiate Oral Iron Supplementation

Begin oral iron supplementation immediately once iron deficiency is confirmed 2:

• Continue iron for 3-6 months after hemoglobin normalizes to replete iron stores 2
• The vast majority of patients respond effectively to inexpensive and well-tolerated oral iron preparations 4

Step 3: Investigate and Treat Underlying Cause

Treatment of the underlying cause will cure the anemia, making identification of the source critical 2:

• Address any identified GI pathology (malignancy, inflammatory bowel disease, celiac disease, angiodysplasia) 2
• Investigate for occult gastrointestinal blood loss, menstruation, pregnancy, or malabsorption 3, 2

Alternative: Parenteral Iron

In rare circumstances of malabsorption, losses exceeding maximal oral replacement, or true intolerance, parenteral iron dextran is effective 4.

Special Considerations for Genetic Causes

If iron deficiency is excluded and genetic causes are suspected (extremely rare):

• X-linked sideroblastic anemia (XLSA) due to ALAS2 defects should be considered in patients with pyridoxine-responsive or unresponsive mild microcytic sideroblastic anemia 5
• Initial treatment with pharmacologic doses of pyridoxine (50-200 mg per day) is recommended for XLSA 5
• SLC25A38 defects in children with severe unexplained microcytic sideroblastic anemia require hematopoietic stem cell transplantation as the only curative option 5

Critical Pitfall: Never Give Empiric Iron Without Confirming Deficiency

Do not give empiric iron therapy without confirming iron deficiency with ferritin, as this can cause harm in conditions like thalassemia and delays proper diagnosis 2.