What are the diagnostic criteria for polycythemia vera?

Diagnostic Criteria for Polycythemia Vera

The diagnosis of polycythemia vera requires meeting either both major criteria plus one minor criterion, OR the first major criterion plus two minor criteria, based on the WHO diagnostic framework. 1

Major Criteria

The two major criteria that form the foundation of PV diagnosis are:

1. Elevated hemoglobin/hematocrit levels:

   • Hemoglobin >16.5 g/dL in men or >16.0 g/dL in women 1, 2
   • Hematocrit >49% in men or >48% in women 1, 2
   • Alternative: Increased red cell mass >25% above predicted normal value 1
   • Alternative: Sustained increase in baseline hemoglobin exceeding 2 g/dL (20 g/L) even without reaching absolute thresholds 3

2. Presence of JAK2 mutation:

   • JAK2V617F mutation (present in >95% of PV cases) 1, 4
   • OR other functionally similar JAK2 mutations such as JAK2 exon 12 mutations 3

Minor Criteria

Three minor criteria support the diagnosis when major criteria alone are insufficient:

1. Bone marrow histology showing:

   • Hypercellularity for age with trilineage growth (panmyelosis) 3
   • Prominent erythroid, granulocytic, and megakaryocytic proliferation 3, 1

2. Subnormal serum erythropoietin level:

   • Below the normal reference range 3, 1
   • This helps differentiate PV from secondary erythrocytosis 4

3. Presence of endogenous erythroid colonies 3, 1

Diagnostic Algorithm

For patients meeting both major criteria: You need at least one minor criterion to confirm the diagnosis, which captures >97% of PV cases. 3

For patients with only the first major criterion (elevated hemoglobin/hematocrit): You must demonstrate at least two minor criteria to establish the diagnosis. 3 This pathway is designed to capture JAK2-negative cases or those with mutation burdens too low to detect. 3

Critical Diagnostic Considerations

Exclusion of secondary causes is mandatory before diagnosing PV. 1 You must rule out:

• Hypoxia-related erythrocytosis (sleep apnea, chronic lung disease, high altitude) 4
• Smoking-related erythrocytosis 4
• Testosterone use 4
• Tumors producing erythropoietin 1
• Renal pathology 5

Iron deficiency creates a diagnostic pitfall: Hemoglobin levels may be falsely lowered in iron-deficient patients. 3 For research or clinical trials, formal PV diagnosis requires demonstrating WHO criteria after iron replacement. 3 However, in routine practice, you should not be prevented from making a working diagnosis of PV in the presence of iron deficiency, even if WHO hemoglobin thresholds are not met. 3

JAK2-negative cases do exist: A negative JAK2 mutation does not completely exclude PV but requires stronger supporting evidence (two minor criteria rather than one). 1 The mutation burden can be low in some patients, requiring sensitive detection techniques. 1

Supportive but not required features include splenomegaly, thrombocytosis, and leukocytosis—these support the diagnosis but are no longer formal diagnostic criteria. 1