What findings can be observed on a peripheral blood smear in a patient with masked polycythemia vera (PV)?

Blood Smear Findings in Masked Polycythemia Vera

In masked polycythemia vera, the peripheral blood smear typically shows thrombocytosis and/or leukocytosis with normal or near-normal hemoglobin/hematocrit, often accompanied by microcytosis from iron deficiency that conceals the underlying erythrocytosis. 1, 2

Key Peripheral Blood Smear Findings

Platelet Abnormalities

• Thrombocytosis is the most common finding, with platelet counts frequently elevated above 400 × 10⁹/L 3
• Masked PV patients display thrombocytosis more frequently than overt PV patients, making this a critical diagnostic clue 2
• Platelet counts may exceed 1,000 × 10⁹/L in some cases, paradoxically increasing bleeding risk through acquired von Willebrand disease 3, 4

White Blood Cell Findings

• Leukocytosis is present in approximately 49% of masked PV cases 3, 4
• The differential typically shows increased neutrophils without significant left shift 3
• White blood cell counts are often >10 × 10⁹/L, though this finding alone is not specific 3
• Leukocytosis >15 × 10⁹/L indicates higher thrombotic risk and inferior survival 3

Red Blood Cell Morphology

• Microcytosis (low MCV) is a hallmark finding that distinguishes masked PV from other conditions 5
• The low MCV results from iron deficiency caused by increased iron utilization by the proliferating erythroid compartment 5
• Iron deficiency can reduce the pathologically elevated red cell mass to within normal reference ranges, creating deceptively normal hemoglobin and hematocrit values 5
• Red blood cell count may appear normal or only mildly elevated despite underlying clonal erythrocytosis 1, 6

Leukoerythroblastic Features

• In some cases progressing toward myelofibrosis, leukoerythroblastosis may be observed (nucleated red blood cells and immature granulocytes in peripheral blood) 7
• This finding suggests transformation to post-PV myelofibrosis, which occurs more frequently in masked PV than overt PV 2

Critical Diagnostic Algorithm

When evaluating a blood smear with these findings:

1. If thrombocytosis + microcytosis are present, immediately order:

   • JAK2 V617F mutation testing (positive in >95% of PV) 3, 4
   • Serum erythropoietin level (low or inappropriately normal in PV) 8, 5
   • Iron studies (ferritin, iron, transferrin saturation) to confirm iron deficiency 5

2. If leukocytosis accompanies thrombocytosis, the likelihood of masked PV increases substantially 2

3. Even with normal hemoglobin/hematocrit, the combination of thrombocytosis, leukocytosis, and microcytosis mandates full PV workup including bone marrow biopsy 5, 1

Common Diagnostic Pitfalls

• Do not exclude PV based on normal hemoglobin alone when microcytosis and thrombocytosis are present—iron deficiency masks the true red cell mass elevation 5, 1
• Do not dismiss borderline-high hemoglobin (16.0-18.4 g/dL in men, 15.0-16.4 g/dL in women) when accompanied by thrombocytosis or leukocytosis, as this defines the masked PV population 2
• Recognize that masked PV carries worse prognosis than overt PV, with higher rates of progression to myelofibrosis (more frequent than overt PV), acute leukemia, and inferior survival 2
• Thrombotic complications occur more frequently in masked PV despite lower hemoglobin levels, likely due to delayed diagnosis and higher platelet counts 9, 2

Clinical Context

The blood smear findings must be interpreted alongside clinical features that trigger suspicion for masked PV 1, 6:

• Unusual site thrombosis (portal vein, splanchnic veins, cerebral veins)
• Splenomegaly without obvious cause
• Aquagenic pruritus
• Erythromelalgia
• History of unexplained thrombosis even years prior

The presence of JAK2 V617F mutation with bone marrow hypercellularity and trilineage growth confirms masked PV diagnosis, even when hemoglobin remains within normal reference ranges 1, 2