What is the appropriate management for a patient with leukocytosis, erythrocytosis, hyperhemoglobinemia, hyperhematocritemia, and neutrophilia?

Management of Polycythemia Vera with Leukocytosis

This patient's laboratory findings—elevated hemoglobin (17.3 g/dL), hematocrit (50.6%), RBC count (5.85), and neutrophilia (8.64)—are highly suggestive of polycythemia vera (PV), and immediate workup should include JAK2 mutation testing and serum erythropoietin level to confirm the diagnosis. 1, 2

Diagnostic Approach

Initial Evaluation

• JAK2 mutation testing is essential: Almost all PV patients harbor a JAK2 mutation, and its presence combined with elevated hemoglobin/hematocrit strongly confirms the diagnosis 1
• Serum erythropoietin level: A low erythropoietin indicates primary erythrocytosis (PV), while normal or elevated levels suggest secondary causes 2, 3
• If JAK2 is negative and erythropoietin is normal or elevated, PV is excluded 1

Diagnostic Criteria for PV

The diagnosis requires meeting specific WHO criteria that include elevated hemoglobin/hematocrit, presence of JAK2V617F mutation (or other JAK2 mutations), and bone marrow findings showing hypercellularity with trilineage growth 1, 3

Risk Stratification

Thrombotic Risk Assessment

High-risk patients are defined by age >60 years OR history of thrombosis; all others are low-risk 1

Additional risk factors to consider:

• JAK2V617F mutation status increases thrombotic risk 1
• Cardiovascular risk factors (hypertension, diabetes, smoking, hyperlipidemia) 1
• Leukocytosis at diagnosis (as present in this patient) is associated with increased risk of recurrent thrombosis 4

Prognostic Factors

• Leukocytosis (as seen in this patient with WBC 11.9) is associated with shortened survival and more aggressive disease course 4
• Advanced age and history of thrombosis also predict worse outcomes 1
• The 10-year risk of leukemic transformation is <3% and fibrotic transformation is approximately 10% 1

Treatment Strategy

Low-Risk Patients

• Low-dose aspirin (typically 81-100 mg daily) to prevent thrombotic complications 1
• Phlebotomy with hematocrit target <45%: This is critical and should be maintained strictly at this level 1

High-Risk Patients

Cytoreductive therapy with hydroxyurea is recommended in addition to aspirin and phlebotomy 1

However, treatment decisions should account for:

• Older patients without JAK2V617F or cardiovascular risk factors may not require hydroxyurea 1
• This patient's leukocytosis warrants consideration for earlier cytoreductive therapy given its association with thrombotic risk 4

Alternative Cytoreductive Options

If hydroxyurea fails or is not tolerated:

• Busulfan is effective 1
• Interferon-α is an alternative option 1

Special Considerations

Monitoring for Complications

• Screen for acquired von Willebrand syndrome if platelet count exceeds 1,000 × 10⁹/L before starting aspirin, as this increases bleeding risk 1
• Monitor for disease progression: Persistent or worsening leukocytosis during disease course may signal progression to post-polycythemic myelofibrosis and is associated with more aggressive disease 4

Neutrophilic Leukocytosis Significance

The neutrophilia (8.64) in this patient requires attention:

• Leukocytosis at PV diagnosis increases thrombotic risk 4
• If leukocytosis persists or worsens (particularly ≥13 × 10⁹/L), this may indicate disease progression and warrants closer monitoring 4
• Development of significant persistent leukocytosis later in disease course is associated with shorter overall survival 4

Critical Pitfalls to Avoid

• Do not maintain hematocrit >45%: The target must be <45% to minimize thrombotic complications 1
• Do not overlook cardiovascular risk factor modification: These compound thrombotic risk in PV patients 1
• Do not dismiss leukocytosis as benign: It carries independent prognostic significance for both thrombosis and survival 4
• Do not start aspirin with extreme thrombocytosis without screening for acquired von Willebrand syndrome 1