What are the guidelines for diagnosing and managing polycythaemia (polycythemia)?

Guidelines for the Diagnosis of Polycythemia

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, according to the 2016 WHO diagnostic criteria. 1, 2

Diagnostic Criteria for Polycythemia Vera

Major Criteria

1. Elevated blood counts:

   • Hemoglobin >16.5 g/dL in men, >16.0 g/dL in women OR
   • Hematocrit >49% in men, >48% in women OR
   • Increased red cell mass (RCM)

2. Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes

3. Presence of JAK2 V617F or JAK2 exon 12 mutation

Minor Criteria

• Subnormal serum erythropoietin level

Diagnostic Algorithm

1. Initial Suspicion:

   • Elevated hemoglobin/hematocrit above the 95th percentile for sex and race
   • Documented increase in hemoglobin/hematocrit above patient's baseline
   • Presence of symptoms: pruritus, erythromelalgia, visual disturbances, splenomegaly

2. First-line Testing:

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

3. Additional Testing:

   • Bone marrow biopsy and aspiration (essential for definitive diagnosis)
   • JAK2 exon 12 mutation testing if JAK2 V617F is negative
   • Oxygen saturation to rule out hypoxic causes

Differentiating Types of Polycythemia

Primary Polycythemia (PV)

• JAK2 mutation positive (>95% of cases)
• Low serum erythropoietin
• Bone marrow showing trilineage proliferation

Secondary Polycythemia

• Normal/high erythropoietin
• JAK2 mutation negative
• Identifiable underlying cause (hypoxia, smoking, sleep apnea, etc.)

Relative Polycythemia

• Normal red cell mass with decreased plasma volume
• Often due to dehydration, diuretics, or "smoker's polycythemia"

Common Diagnostic Pitfalls

1. Masked Polycythemia Vera:

   • Iron deficiency can normalize hemoglobin in PV
   • May present with normal hemoglobin/hematocrit but still have JAK2 mutation
   • Consider in cases of unusual thrombosis (especially splanchnic vein thrombosis) 3

2. Overlooking Secondary Causes:

   • Always evaluate for hypoxic conditions, sleep apnea, smoking, and other causes when JAK2 mutation is absent

3. Relying Solely on Hemoglobin/Hematocrit:

   • Expanded plasma volume can mask erythrocytosis
   • Consider red cell mass measurement in borderline cases 4

4. Neglecting Bone Marrow Examination:

   • Essential for definitive diagnosis, especially in cases with suspicious blood findings
   • Can identify early myelofibrosis (present in up to 20% of PV patients) 1

5. Overdiagnosis Based on New WHO Criteria:

   • The 2016 WHO criteria lowered the hemoglobin/hematocrit thresholds
   • These thresholds overlap with normal values in some individuals
   • In borderline cases, diagnostic workup should only proceed with additional clinical/laboratory features suggesting myeloproliferative neoplasm 5

By following these guidelines systematically, clinicians can accurately diagnose polycythemia and distinguish between its various forms, leading to appropriate management and improved patient outcomes.