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

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

According to the World Health Organization (WHO) criteria, 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 Diagnostic Criteria

1. Elevated red blood cell parameters:

   • Hemoglobin >18.5 g/dL in men, >16.5 g/dL in women
   • 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 Diagnostic Criteria

1. Bone marrow biopsy showing hypercellularity with trilineage growth (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation 2

2. Serum erythropoietin level below the reference range for normal 2, 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 (thrombocytosis, leukocytosis, microcytosis from iron deficiency, splenomegaly, aquagenic pruritus, unusual thrombosis) with borderline-high hematocrit 2, 1

2. First-line testing:

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

3. Interpretation of serum erythropoietin:

   • Low: PV diagnosis probable
   • Normal: PV diagnosis possible
   • High: Evaluate for secondary polycythemia 2

4. Bone marrow examination:

   • Indicated in most cases for definitive diagnosis
   • Assess for characteristic histology: hypercellularity, increased megakaryocytes including cluster formation, giant megakaryocytes, pleomorphism in megakaryocyte morphology
   • Evaluate for reticulin fibrosis (present in 12% of patients)
   • Perform cytogenetic studies (abnormalities found in 13-18% of patients) 2, 1

5. For equivocal cases (approximately 10% of patients):

   • Specialized testing may include:
     • Bone marrow immunohistochemistry for thrombopoietin receptor (c-mpl)
     • Neutrophil expression of polycythemia rubra vera-1 gene (PRV-1)
     • Spontaneous erythroid colony assay 2

Important Diagnostic Considerations

• Masked PV: Iron deficiency can normalize hemoglobin levels in PV patients, leading to missed diagnoses 1

• Differentiation from secondary polycythemia: Secondary causes (smoking, sleep apnea, testosterone use) typically have normal/high erythropoietin levels and no JAK2 mutation 1, 3

• Relative polycythemia: Characterized by normal red cell mass with decreased plasma volume (can be caused by dehydration, diuretics use, or smoking) 1

• Splanchnic vein thrombosis: Unusual site thrombosis should raise suspicion for PV 1

Pediatric Considerations

While the evidence provided does not specifically address pediatric diagnostic criteria for PV, the same WHO diagnostic criteria are generally applied to pediatric patients, with appropriate age-adjusted reference ranges for hemoglobin, hematocrit, and other parameters.

Follow-up After Diagnosis

• Regular monitoring of CBC every 2-3 months during initial management
• Evaluation for transformation to myelofibrosis or acute leukemia
• Assessment for thrombotic and bleeding complications 1

By following this diagnostic approach, clinicians can accurately diagnose polycythemia vera and distinguish it from secondary causes of erythrocytosis, enabling appropriate management and monitoring.