How is mean corpuscular volume (MCV) relevant in assessing a patient with borderline‑high hemoglobin to differentiate true erythrocytosis from other causes?

MCV Relevance in Borderline-High Hemoglobin Assessment

MCV is not directly useful for distinguishing true erythrocytosis from apparent polycythemia, but it serves as a critical marker to identify coexisting iron deficiency or other red cell disorders that may complicate the clinical picture. 1

Primary Role of MCV in Erythrocytosis Evaluation

Distinguishing True vs. Apparent Polycythemia

• MCV does not differentiate between true and apparent polycythemia—this distinction requires assessment of red blood cell mass (RCM) and plasma volume, not red cell indices. 1
• Apparent polycythemia results from plasma volume contraction (dehydration, diuretics, burns) or failure to recognize normal hemoglobin values exceeding the 95th percentile, neither of which affects MCV. 1
• True polycythemia (whether primary or secondary) is confirmed by demonstrating increased RCM, not by MCV measurement. 1

Critical Diagnostic Value: Identifying Concurrent Iron Deficiency

• Low MCV (<80 fL) in the setting of elevated hemoglobin strongly suggests polycythemia vera with concurrent iron deficiency, a common scenario where phlebotomy or chronic bleeding depletes iron stores. 2
• Microcytic polycythemia (high RBC count with low MCV) requires differentiation between: 2
  • Polycythemia vera with iron deficiency (most common)
  • Thalassemia minor with secondary polycythemia
  • Secondary polycythemia from hypoxia with incidental iron deficiency
• When iron is repleted in secondary polycythemia with iron deficiency, the RBC count remains elevated but MCV normalizes, confirming the diagnosis. 2
• Red cell size distribution curves (RDW) reliably distinguish thalassemia minor from polycythemia with iron deficiency. 2

Algorithmic Approach to MCV Interpretation

When MCV is Low (<80 fL) with Elevated Hemoglobin:

1. Measure serum ferritin and transferrin saturation to confirm iron deficiency. 1, 3
2. If iron deficient: Consider polycythemia vera with iron depletion (from phlebotomy or bleeding). 2
3. If iron replete with low ferritin: Measure hemoglobin A2 to exclude thalassemia trait. 3
4. Combined serum ferritin and MCV measurements identify iron deficiency vs. thalassemia trait with >95% accuracy. 3

When MCV is Normal (80-100 fL) with Elevated Hemoglobin:

• Normal MCV does not exclude true polycythemia—proceed with EPO level, JAK2 mutation testing, and consider RCM measurement if diagnosis remains unclear. 1
• Normal MCV with normal ferritin suggests primary polycythemia vera or secondary polycythemia without iron deficiency. 1

When MCV is High (>100 fL) with Elevated Hemoglobin:

• Macrocytosis with erythrocytosis is uncommon and suggests: 4, 5
  • Vitamin B12 or folate deficiency masking anemia (creating "pseudo-polycythemia")
  • Medication effects (hydroxyurea, thiopurines, anticonvulsants)
  • Chronic alcohol use
  • Myelodysplastic syndrome (though typically presents with anemia, not erythrocytosis)
• Measure vitamin B12, folate, and reticulocyte count immediately. 4, 5

Common Pitfalls to Avoid

• Do not assume normal MCV excludes iron deficiency—ferritin and transferrin saturation are mandatory even with normal MCV, as inflammation (elevated CRP) can falsely elevate ferritin. 1
• Do not overlook microcytic erythrocytosis—this combination demands investigation for polycythemia vera with iron deficiency or thalassemia trait. 2
• Do not use MCV alone to diagnose the cause of erythrocytosis—it is an adjunctive marker that identifies concurrent hematologic abnormalities, not a primary diagnostic tool for polycythemia. 1

Minimum Required Workup Beyond MCV

When evaluating borderline-high hemoglobin, the complete blood count with MCV must be supplemented with: 1, 4

• Serum ferritin and transferrin saturation (to assess iron stores and availability)
• C-reactive protein (to interpret ferritin in inflammatory states)
• Reticulocyte count (to assess bone marrow response)
• Red cell distribution width (RDW) (elevated in iron deficiency, normal in thalassemia)
• EPO level (low in polycythemia vera, high/normal in secondary polycythemia)

If the cause remains unclear after this workup, hematology consultation is mandatory. 4, 5