What are the diagnostic criteria for polycythemia in males?

Diagnostic Criteria for Polycythemia in Males

In males, polycythemia vera is diagnosed when hemoglobin is ≥18.5 g/dL OR hematocrit is >52% (or above the 99th percentile for age, sex, and altitude), along with other supporting criteria. 1, 2

Major Diagnostic Criteria

• Hemoglobin ≥18.5 g/dL in males or hematocrit >52% (or greater than the 99th percentile of method-specific reference range for age, sex, and altitude of residence) 3, 2
• Presence of JAK2V617F or other functionally similar mutation such as JAK2 exon 12 mutation (found in >95% of PV patients) 3, 1
• Elevated red cell mass >25% above mean normal predicted value can also be used as diagnostic evidence 2

Minor Diagnostic Criteria

• Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation 3, 1
• Serum erythropoietin level below the reference range for normal 3, 2
• Endogenous erythroid colony formation in vitro 3

Diagnostic Algorithm

1. Diagnosis requires either:

   • Both major criteria and at least one minor criterion 3, 1
   • OR the first major criterion (elevated hemoglobin/hematocrit) together with at least two minor criteria 3

2. When to suspect and test for polycythemia vera:

   • If hematocrit is between 48-60% or hemoglobin ≥18.5 g/dL, proceed with JAK2 mutation testing 2
   • A documented and sustained increase in hemoglobin of at least 2 g/dL from baseline (not attributable to iron deficiency correction) may indicate PV even if absolute thresholds aren't met 2

Important Clinical Considerations

• Iron deficiency can mask true polycythemia by lowering hemoglobin/hematocrit levels; consider iron replacement before excluding PV 3, 2
• For research or clinical trials, a formal PV diagnosis requires meeting the WHO criteria in terms of hemoglobin/hematocrit level after iron replacement 3
• Red cell mass measurement should be considered in patients with suspected PV and with hematocrit between 0.48 L/L and 0.52 L/L to avoid missing cases 4
• Masked polycythemia vera (mPV) can occur in patients with hemoglobin levels below the diagnostic threshold (16.0-18.4 g/dL in males) but who otherwise meet criteria and have characteristic bone marrow morphology 5

Clinical Implications and Complications

• PV is associated with increased risk of arterial thrombosis (16% of patients) and venous thrombotic events (7% of patients) 6
• Patients with PV require therapeutic phlebotomy to maintain hematocrit <45% and low-dose aspirin (if no contraindications) to reduce thrombotic risk 6
• About 12.7% of patients with PV develop myelofibrosis and 6.8% develop acute myeloid leukemia 6
• Risk factors for inferior survival in masked PV include age >65 years and white blood cell count >15 × 10^9/L 5

Differential Diagnosis

• Essential to differentiate PV from secondary causes of erythrocytosis such as hypoxia, tumors producing erythropoietin, etc. 1
• Presence of splenomegaly, thrombocytosis, and leukocytosis supports the diagnosis of PV but are not formal diagnostic criteria 1