What is the threshold to diagnose polycythemia in males?

Diagnostic Threshold for Polycythemia in Males

According to the World Health Organization (WHO) criteria, the diagnostic threshold for polycythemia vera (PV) in males is a hemoglobin level ≥18.5 g/dL or hematocrit greater than 52% (the 99th percentile of method-specific reference range). 1

Primary Diagnostic Criteria

• The WHO diagnostic criteria for polycythemia vera in males include hemoglobin ≥18.5 g/dL as a major criterion 2
• Alternatively, a hematocrit greater than the 99th percentile of method-specific reference range for age, sex, and altitude of residence can be used 1
• An elevated red cell mass >25% above mean normal predicted value can also serve as diagnostic evidence of increased red cell volume 2, 1

Updated Diagnostic Considerations

• More recent updates to the WHO criteria (2016) have lowered the hemoglobin threshold to 16.5 g/dL in males and introduced a hematocrit cutoff of 49% in males 3, 4
• A documented and sustained increase in hemoglobin of at least 2 g/dL from an individual's baseline value (not attributable to correction of iron deficiency) may indicate PV even if absolute thresholds aren't met 2, 1

Diagnostic Algorithm

1. If hemoglobin ≥18.5 g/dL (or ≥16.5 g/dL in updated criteria) or hematocrit >52% (or >49% in updated criteria), proceed with JAK2 mutation testing 1, 3
2. Measure serum erythropoietin level (typically low in PV) 1
3. Consider bone marrow biopsy showing hypercellularity with trilineage growth 2

Common Pitfalls and Caveats

• Iron deficiency may mask true polycythemia by lowering hemoglobin/hematocrit levels; consider iron replacement before excluding PV 2
• The concept of "masked polycythemia vera" (mPV) refers to patients with JAK2 mutations and characteristic bone marrow morphology but with hemoglobin levels below the WHO thresholds (16.0-18.4 g/dL in males) 5
• These mPV patients may have worse outcomes compared to those with overt PV, suggesting that strict adherence to hemoglobin thresholds might miss clinically significant disease 5

Diagnostic Criteria Framework

• Diagnosis of PV requires either:
  • Both major criteria (hemoglobin ≥18.5 g/dL in males AND presence of JAK2 mutation) plus at least one minor criterion, OR
  • First major criterion (hemoglobin threshold) plus at least two minor criteria 2
• Minor criteria include bone marrow biopsy showing hypercellularity, low serum erythropoietin level, and endogenous erythroid colony formation in vitro 2

Treatment Threshold Considerations

• Once diagnosed, the treatment goal is to maintain hematocrit <45% through phlebotomy to reduce thrombotic risk 6, 7
• This treatment threshold (<45%) is different from the diagnostic threshold and applies to all PV patients regardless of gender 7, 4