MCV in Iron-Deficient (Masked) Polycythemia Vera
In masked polycythemia vera with iron deficiency, the MCV can drop below 70 fL, with documented cases showing microcytic polycythemia at this threshold. 1
Understanding Masked PV and Iron Deficiency
Iron deficiency is nearly universal in PV patients, occurring at presentation and/or during disease course in virtually all cases. 2 This creates a physiological paradox where polycythemia coexists with iron deficiency, fundamentally altering red cell indices. 2
The key mechanism: Since hematocrit equals RBC count × MCV, iron deficiency-induced microcytosis can mask the elevated red cell mass by normalizing or reducing the hematocrit despite a truly elevated RBC count. 3
Specific MCV Thresholds in Masked PV
- MCV <70 fL is well-documented in polycythemia vera patients with concurrent iron deficiency 1
- Patients with masked PV demonstrate significantly lower MCV ratios compared to other myeloproliferative neoplasm suspects 3
- The microcytosis in iron-deficient PV can be severe enough to mimic thalassemia minor, requiring careful differentiation 1
Critical Diagnostic Pitfalls
Do not assume microcytic polycythemia is always thalassemia. Among 35 patients with MCV <70 fL and elevated RBC counts, 26% had polycythemia (either vera or secondary) with iron deficiency rather than thalassemia. 1
Distinguishing Features:
- RBC size distribution curves reliably distinguish between thalassemia minor and polycythemia with iron deficiency 1
- Red cell distribution width (RDW) is elevated in iron deficiency (>14%) but normal in thalassemia 4, 5
- Serum ferritin <30 μg/L confirms iron deficiency in the absence of inflammation 4, 5
- When iron is repleted in polycythemia patients, the RBC count remains elevated while MCV normalizes to reveal the underlying polycythemia 1
Clinical Implications of Iron Deficiency in PV
Iron deficiency in PV is not merely a laboratory finding—it has significant therapeutic and prognostic implications:
- Therapeutic phlebotomy exacerbates iron deficiency, contributing to non-hematological symptoms beyond the hematologic abnormalities 2
- Cytoreductive therapy works more effectively in iron-deficient versus iron-replete PV patients for reversing symptoms 2
- Masked PV patients (45% of PV cases by WHO criteria) present with higher platelet counts and lower JAK2V617F allele burden compared to overt PV 6
Practical Diagnostic Algorithm
When encountering microcytic polycythemia (elevated RBC with low MCV):
- Measure serum ferritin immediately to assess iron status 4
- Check RDW: High RDW (>14%) suggests iron deficiency; normal RDW suggests thalassemia 4, 5
- If ferritin is low (<30 μg/L), consider masked PV in the differential alongside iron deficiency anemia 4
- Evaluate RBC count specifically: In true PV, the RBC count remains elevated despite microcytosis 3, 1
- Consider JAK2 mutation testing if clinical suspicion for PV exists despite normal/low hematocrit 6
The RBC count may more precisely reflect total red cell mass than hematocrit in iron-deficient states, making it a superior marker for the hypercoagulable state in PV patients. 3