What tests are indicated for a patient with low Mean Corpuscular Volume (MCV)?

Diagnostic Workup for Low MCV (Microcytic Anemia)

For a patient with low MCV, immediately order: peripheral blood smear, red blood cell distribution width (RDW), serum ferritin, iron studies (serum iron, total iron binding capacity/transferrin saturation), and complete blood count with reticulocyte index. 1

Initial Laboratory Tests

Essential First-Line Tests

• RDW measurement is critical to differentiate causes of microcytic anemia 1

  • Low MCV + RDW >14% indicates iron deficiency anemia 1
  • Low MCV + RDW ≤14% suggests thalassemia minor 1

• Serum ferritin is the most specific indicator of depleted iron stores and should be measured in all cases 1

  • Ferritin <30 ng/mL indicates absolute iron deficiency (in absence of inflammation) 1
  • Note: Infection and inflammation can falsely elevate ferritin, reducing specificity 1

• Iron studies including serum iron, TIBC, and transferrin saturation 1

  • Transferrin saturation <15% with ferritin <30 ng/mL confirms absolute iron deficiency 1

• Reticulocyte index to assess bone marrow production capacity 1

  • Low RI (<1.0-2.0) indicates decreased RBC production 1
  • High RI suggests blood loss or hemolysis 1

Peripheral Blood Smear Review

• Visual examination of RBC morphology is critical to confirm size, shape, and color 1
• Helps identify microcytic, hypochromic cells characteristic of iron deficiency 2
• Can reveal other diagnostic clues (target cells in thalassemia, basophilic stippling in lead poisoning) 1

Additional Testing Based on Initial Results

If Iron Deficiency is Excluded

• Hemoglobin electrophoresis to evaluate for thalassemia if RDW is normal or minimally elevated 1, 2

• Erythrocyte protoporphyrin concentration if available 1

  • Elevated (>80 μg/dL in children 1-2 years, >70 μg/dL in adults) indicates iron-deficient erythropoiesis 1
  • Also elevated in lead poisoning, infection, and inflammation 1

• Lead level if clinical suspicion exists, particularly in children or those with occupational exposure 1

• Evaluation for chronic disease/inflammation including C-reactive protein 1

If Iron Deficiency is Confirmed

• Investigation for source of blood loss is mandatory 2
  • Stool guaiac testing for gastrointestinal bleeding 1
  • Gynecologic evaluation in menstruating women 2
  • Upper and/or lower endoscopy as clinically indicated 2

Common Pitfalls to Avoid

• Do not rely on MCV alone - up to 84% of deficiency cases can be missed if MCV is the only screening parameter 3

• Ferritin interpretation in inflammation - chronic inflammatory conditions can elevate ferritin despite true iron deficiency; consider transferrin saturation and other markers 1

• Bone marrow biopsy is rarely needed - absence of iron stores in bone marrow remains the gold standard but is usually unnecessary given the accuracy of serum ferritin and iron studies 2

• Multiple causes can coexist - particularly in patients with chronic disease, where both iron deficiency and anemia of chronic disease may be present 1

Algorithm Summary

1. Confirm low MCV with repeat CBC if needed
2. Order RDW, ferritin, iron studies, reticulocyte index, and peripheral smear simultaneously 1
3. If RDW >14% + low ferritin/transferrin saturation: diagnose iron deficiency and search for bleeding source 1
4. If RDW ≤14% + normal iron studies: consider thalassemia and order hemoglobin electrophoresis 1
5. If unclear: consider erythrocyte protoporphyrin, lead level, or evaluation for chronic disease 1