How can you distinguish between leukocytosis (elevated white blood cell count) due to polycythemia vera (PV) and leukocytosis caused by an infection in a patient with PV?

Distinguishing PV-Related Leukocytosis from Infection

In polycythemia vera, leukocytosis is typically chronic and stable with a baseline elevation, whereas infection causes an acute rise above the patient's established baseline, often accompanied by fever, left shift, and toxic granulation on peripheral smear. 1, 2

Key Clinical Distinctions

Baseline Pattern Recognition

• PV-associated leukocytosis is present at diagnosis in approximately 49% of patients and represents chronic trilineage myeloproliferation 2, 3
• The white blood cell count in PV remains relatively stable over time unless disease progression occurs 1
• Document each patient's baseline WBC during stable periods to identify acute deviations 1

Features Favoring Infection

• Acute elevation of WBC above the patient's established PV baseline (not above laboratory reference ranges) 1
• Fever, localizing symptoms, or clinical signs of infection 1
• Left shift with increased band forms and toxic granulation on peripheral smear - these morphologic changes are characteristic of infection, not PV 1
• Elevated inflammatory markers (CRP, ESR) disproportionate to baseline PV state 1

Features Favoring PV-Related Leukocytosis

• Chronic, stable elevation present since diagnosis 2, 3
• Concurrent thrombocytosis and erythrocytosis (trilineage involvement) 2, 3
• Absence of fever or infectious symptoms 1
• Mature neutrophils without left shift or toxic changes 1
• Elevated leukocyte alkaline phosphatase (though this lacks specificity) 4, 5
• Increased serum vitamin B12 levels reflecting increased cell turnover 4, 5

Practical Diagnostic Algorithm

Step 1: Compare to Baseline

• If WBC is at the patient's established PV baseline → likely PV-related 1
• If WBC shows acute rise above baseline → suspect infection 1

Step 2: Assess Clinical Context

• Presence of fever, chills, or localizing infectious symptoms strongly favors infection 1
• Progressive leukocytosis over weeks to months may indicate PV disease progression requiring cytoreductive therapy adjustment 1

Step 3: Review Peripheral Smear

• Toxic granulation, Döhle bodies, and left shift indicate infection 1
• Mature neutrophils without toxic changes favor PV 1

Step 4: Consider Additional Testing

• Blood cultures if infection suspected 1
• Inflammatory markers (CRP, procalcitonin) to support infectious etiology 1
• JAK2 mutation burden (variant allele frequency) does not acutely change with infection 6

Critical Pitfalls to Avoid

• Do not rely on absolute WBC values compared to laboratory reference ranges - use the patient's individual PV baseline instead 1, 3
• Leukocytosis at diagnosis is associated with higher thrombosis risk in PV but does not predict infection 1
• Do not assume all WBC elevations in PV patients are disease-related - infection remains common and must be excluded 1
• Progressive leukocytosis warrants consideration of cytoreductive therapy intensification, not antibiotics 1
• Extreme leukocytosis (>25-30 × 10⁹/L) is unusual for stable PV and should prompt investigation for infection or disease transformation 1