What is the likely diagnosis and treatment for a patient with microcytic anemia, indicated by low Mean Corpuscular Volume (MCV), low Mean Corpuscular Hemoglobin (MCH), low Mean Corpuscular Hemoglobin Concentration (MCHC), and elevated Red Cell Distribution Width (RDW)?

Microcytic Anemia with Elevated RDW: Iron Deficiency Until Proven Otherwise

The combination of low MCV, low MCH, low MCHC, and elevated RDW strongly indicates iron deficiency anemia, which requires immediate confirmation with serum ferritin and transferrin saturation, followed by investigation of the underlying cause of iron loss. 1

Why This Pattern Points to Iron Deficiency

The elevated RDW (>14.0%) is the critical distinguishing feature in this presentation:

• High RDW with low MCV is highly specific for iron deficiency anemia, reflecting the heterogeneous red cell population that develops as iron stores become progressively depleted 2, 1
• The RDW serves as an indicator of iron deficiency, particularly useful when microcytosis and other abnormalities coexist 2
• Low MCH is a more reliable marker of iron deficiency than MCHC and indicates iron-restricted erythropoiesis 3
• This pattern has 72% sensitivity for detecting iron deficiency even before frank anemia fully develops 3

The key distinction: Low MCV with normal RDW (≤14.0%) would suggest thalassemia trait instead, making RDW evaluation essential to avoid inappropriate iron therapy that could cause iron overload 1, 4

Immediate Diagnostic Workup

Obtain the following tests to confirm iron deficiency and assess severity:

• Serum ferritin - the single most powerful test for iron deficiency 1, 3

  • <15 μg/L (or <30 μg/L) definitively confirms iron deficiency without inflammation 1, 3
  • In the presence of inflammation (elevated CRP), ferritin up to 45-100 μg/L may still indicate iron deficiency 2, 1, 3
  • Ferritin >100 μg/L essentially rules out iron deficiency even with inflammation 1

• Transferrin saturation (TSAT) - less affected by inflammation than ferritin 3

  • <15-16% supports iron deficiency 3

• C-reactive protein (CRP) - to interpret ferritin in the context of inflammation 2, 3

• Reticulocyte count - to evaluate bone marrow response 2, 3

  • Low or normal reticulocytes with microcytic anemia confirms deficiency states rather than hemolysis 2

Treatment Approach

Once iron deficiency is confirmed:

• Oral iron supplementation is first-line for most patients 5, 6

  • Ferrous sulfate 324 mg tablets (65 mg elemental iron) is the standard, inexpensive, and well-tolerated option 5, 6
  • Continue treatment to replete iron stores, not just correct hemoglobin 6

• Intravenous iron is reserved for specific situations 3:

  • Malabsorption or gastrointestinal intolerance to oral iron
  • Iron losses exceeding maximal oral replacement capacity
  • Rapid repletion needed (e.g., heart failure, pregnancy)

• Monitor iron status during treatment to assess response and detect potential iron overload 3

Mandatory Investigation for Underlying Cause

Critical pitfall: Iron deficiency in adults is not a diagnosis—it is a symptom requiring investigation for the source of iron loss.

For adult men and postmenopausal women with confirmed iron deficiency:

• Gastrointestinal investigation should be performed in all patients unless there is significant non-gastrointestinal blood loss 1, 3

• Upper endoscopy with small bowel biopsies 1:

  • Reveals a cause in 30-50% of patients
  • 2-3% of patients with iron deficiency have celiac disease

• Colonoscopy or barium enema to exclude gastrointestinal malignancy 1

For premenopausal women:

• Assess menstrual blood loss as the likely source 3
• If menstrual losses do not explain severity, proceed with gastrointestinal evaluation 3

Alternative Diagnoses to Consider

If iron studies are normal despite the microcytic pattern:

• Thalassemia trait - but this is unlikely given the elevated RDW 1, 4

  • Thalassemia typically presents with normal RDW (≤14.0%) and elevated red cell count
  • If suspected based on ethnicity or family history, obtain hemoglobin electrophoresis 2, 3

• Anemia of chronic disease - can cause microcytosis but rarely drops MCV below 70 fL 2, 1

  • Assess for underlying inflammatory conditions
  • Ferritin may be normal or elevated despite functional iron deficiency 2

• Hereditary microcytic anemias - rare genetic disorders of iron metabolism or heme synthesis 2

  • Consider if anemia is refractory to iron supplementation with appropriate compliance
  • May require hematology consultation 2

Common Pitfalls to Avoid

• Do not assume all microcytic anemias are iron deficiency - always confirm with ferritin before treating 1
• Do not treat empirically without confirming the diagnosis - inappropriate iron therapy in thalassemia can cause iron overload 1, 7
• Do not stop at correcting hemoglobin - iron stores must be repleted to prevent rapid recurrence 6
• Do not fail to investigate the source - undiagnosed gastrointestinal malignancy is the most serious missed diagnosis 1, 3