Can polycythemia vera (PV) exhibit fluctuations in leukocytosis (an increase in white blood cells) and erythrocytosis (an increase in red blood cells) over time?

Fluctuations in Blood Counts in Polycythemia Vera

Yes, polycythemia vera can exhibit fluctuations in both leukocytosis and erythrocytosis over time, though the underlying clonal disorder persists. These variations occur due to multiple factors including treatment effects, superimposed conditions, and the natural disease course.

Mechanisms of Blood Count Fluctuations

Erythrocytosis Variability

The red blood cell mass in PV can appear to fluctuate or even normalize despite persistent disease activity due to several confounding factors:

• Iron deficiency or bleeding can lower the pathologic baseline red cell mass (RCM) to within the normal reference range, masking the underlying erythrocytosis 1
• Superimposed comorbid conditions causing hypoxia (such as chronic lung disease) can alter the clinical presentation in patients who have both PV and another condition 1
• Therapeutic phlebotomy intentionally reduces hematocrit levels, creating controlled fluctuations in red cell parameters 1
• The measured RCM value may lie at the extreme left tail of the Gaussian distribution for PV patients and overlap with upper normal values, making fluctuations appear more pronounced 1

Leukocytosis Variability

Approximately half of patients with PV display leukocytosis, but this is not a constant feature:

• Leukocytosis is recognized as one of the diagnostic criteria that lacks both sensitivity and specificity in PV 1
• White blood cell counts can vary independently of red cell parameters, as the clonal disorder affects multiple cell lineages differently over time 1
• The degree of leukocytosis does not consistently correlate with thrombosis risk, suggesting independent regulation 1

Clinical Implications of Count Fluctuations

Disease Monitoring Considerations

Serial measurements are more valuable than isolated readings for assessing disease activity:

• In myeloproliferative disorders like PV, monitoring blood counts alongside other parameters helps assess disease activity and thrombotic risk 2
• The presence of concurrent thrombocytosis and leukocytosis can constitute an indication for cytoreductive therapy even in otherwise low-risk disease 3
• Leukocytosis contributes to overall thrombotic risk even though it hasn't been formally included in risk stratification scoring systems 4

Treatment-Related Fluctuations

Cytoreductive therapy intentionally creates fluctuations in blood counts:

• Hydroxyurea and interferon-α reduce elevated cell counts as part of their therapeutic mechanism 3, 5
• The goal is normalization or near-normalization of the hemogram without causing prohibitive cytopenias 6
• Maintaining hematocrit <45% through phlebotomy creates controlled fluctuations in red cell parameters 6, 5

Important Clinical Caveats

Several pitfalls can lead to misinterpretation of blood count fluctuations:

• Pre-analytical variables such as time between blood collection and analysis can significantly affect measurements 2
• In conditions with increased hematocrit, standard amounts of anticoagulant with reduced plasma volume can artificially affect cell count parameters 2
• Plasma volume expansion in PV can mask erythrocytosis, making the red cell elevation appear less severe or fluctuating 7
• A normal-range RCM reading does not rule out PV since it misses the PV population distributed at the left extreme tail of the Gaussian distribution 1

Disease Progression and Evolution

PV can evolve over time, creating apparent fluctuations in blood counts:

• PV can present initially as isolated erythrocytosis, leukocytosis, thrombocytosis, or any combination, and it can take years for a true panmyelopathy to appear 7
• The disease carries cumulative risks of fibrotic progression (post-PV myelofibrosis) and leukemic evolution, which fundamentally alter blood count patterns 4, 5
• Twenty-year risk for progression to post-PV myelofibrosis is approximately 16%, which would dramatically change the blood count profile 5