What are the diagnostic criteria for polycythemia vera (PV) in adults and children according to Canadian guidelines?

Diagnostic Criteria for Polycythemia Vera in Adults and Children According to Canadian Guidelines

According to the World Health Organization (WHO) criteria, which are adopted in Canadian practice, the diagnosis of polycythemia vera (PV) requires either both major criteria plus at least one minor criterion, or the first major criterion plus at least two minor criteria. 1

Major Criteria

1. Elevated red blood cell parameters:

   • Hemoglobin >18.5 g/dL in men, >16.5 g/dL in women, OR
   • Hematocrit >49% in men, >48% in women, OR
   • Increased red cell mass >25% above mean normal predicted value 2, 1

2. Presence of JAK2 mutation:

   • JAK2 V617F (found in >90% of PV cases), OR
   • JAK2 exon 12 mutation (in JAK2 V617F-negative cases) 2, 1

Minor Criteria

1. Bone marrow biopsy showing:

   • Hypercellularity for age with trilineage growth (panmyelosis)
   • Prominent erythroid, granulocytic, and megakaryocytic proliferation 2, 1

2. Serum erythropoietin level below the reference range for normal 1

3. Endogenous erythroid colony formation in vitro 2

Diagnostic Algorithm

1. Initial suspicion should be raised when:

   • Hemoglobin/hematocrit is above the 95th percentile adjusted for sex and race
   • Documented increase in hemoglobin/hematocrit above patient's baseline
   • PV-related features present with borderline-high hematocrit:
     • Thrombocytosis
     • Leukocytosis
     • Microcytosis from iron deficiency
     • Splenomegaly
     • Aquagenic pruritus
     • Unusual thrombosis 1

2. First-line testing:

   • Complete blood count with peripheral blood smear
   • JAK2 V617F mutation testing
   • Serum erythropoietin level 1, 3

3. Interpretation of results:

   • Low serum erythropoietin level makes PV diagnosis probable
   • Normal level makes PV diagnosis possible
   • High level requires evaluation for secondary polycythemia 1

4. Bone marrow examination:

   • Critical for definitive diagnosis
   • Should include evaluation of megakaryocyte morphology and clustering
   • Assessment for reticulin fibrosis
   • Cytogenetic studies to rule out other myeloid disorders 1

Special Considerations

Masked Polycythemia Vera

• Iron deficiency can normalize hemoglobin in PV
• Consider PV diagnosis in patients with suggestive features even with borderline elevated counts 1, 4

Differentiation from Secondary Polycythemia

• PV: JAK2 mutation positive and low erythropoietin
• Secondary polycythemia: normal/high erythropoietin and identifiable underlying cause (smoking, sleep apnea, testosterone use, etc.) 1, 3

Relative Polycythemia

• Normal red cell mass with decreased plasma volume
• Can be caused by dehydration, diuretics use, or smoker's polycythemia 1

Children with PV

While the diagnostic criteria are primarily established for adults, the same WHO criteria are generally applied to pediatric cases, with appropriate age-adjusted reference ranges for hemoglobin, hematocrit, and other parameters. PV is extremely rare in children, and secondary causes of erythrocytosis should be thoroughly excluded 1.

Common Pitfalls to Avoid

1. Overlooking masked PV where iron deficiency normalizes hemoglobin 1

2. Attributing findings solely to inflammation when persistent abnormalities warrant hematologic evaluation 1

3. Neglecting bone marrow examination which is essential for definitive diagnosis in cases with suspicious blood findings 1

4. Overlooking secondary causes of polycythemia when JAK2 mutation is absent 1

5. Failure to recognize early or masked polycythemia vera particularly in cases with borderline elevated counts but with PV-related features 1, 4

By following these diagnostic criteria and being aware of the potential pitfalls, clinicians can accurately diagnose polycythemia vera in both adult and pediatric populations.