Do red blood cell count, hematocrit, and hemoglobin levels vary in patients with polycythemia vera (PV)?

Do Red Blood Cell Count, Hematocrit, and Hemoglobin Vary in Polycythemia Vera?

Yes, red blood cell count, hematocrit, and hemoglobin levels vary significantly in polycythemia vera (PV), and this variation is a defining characteristic of the disease that forms the cornerstone of diagnosis. 1

Diagnostic Thresholds and Variation

The WHO diagnostic criteria for PV establish specific hemoglobin and hematocrit thresholds that define the disease, but these values can vary considerably among patients:

• Hemoglobin ≥18.5 g/dL in men or ≥16.5 g/dL in women serves as the first major diagnostic criterion 1
• Hematocrit ≥49% in men or ≥48% in women provides an alternative threshold 1
• These parameters can increase substantially above these thresholds, with some patients presenting with hemoglobin >20 g/dL and hematocrit >65% 2

Masked Polycythemia Vera: A Critical Diagnostic Challenge

A substantial proportion of PV patients (15-35%) present with "masked" or "inapparent" polycythemia where hemoglobin and hematocrit remain below traditional diagnostic thresholds despite increased red cell mass. 3

Key Features of Masked PV:

• Hemoglobin levels between 16.0-18.4 g/dL in males and 15.0-16.4 g/dL in females can still represent true PV when accompanied by JAK2 mutations and characteristic bone marrow findings 3
• Increased plasma volume masks the elevated red cell mass, keeping hemoglobin and hematocrit in the normal range 4
• These patients more frequently present with higher platelet counts and increased bone marrow reticulin fibrosis 3
• Worse overall survival compared to overt PV has been documented in masked PV patients 3

Dynamic Changes in Red Cell Parameters

Baseline Variation and Progression:

• A sustained increase of ≥2 g/dL hemoglobin from an individual's baseline warrants investigation for PV, even if absolute values remain within normal reference ranges 5
• Red cell parameters fluctuate based on treatment status (phlebotomy reduces hematocrit, while untreated disease shows progressive elevation) 1
• Iron deficiency can coexist with erythrocytosis, causing microcytic polycythemia with elevated RBC count but paradoxically reduced hemoglobin 2

Treatment-Related Variation:

• Therapeutic phlebotomy aims to maintain hematocrit strictly below 45% to reduce thrombotic risk 6
• During active treatment, hemoglobin and hematocrit values will be artificially lowered and do not reflect the underlying disease activity 1
• Iron depletion from repeated phlebotomy can mask the true extent of erythrocytosis 2

Clinical Implications of Parameter Variation

When to Suspect PV Despite "Normal" Values:

Investigate for PV when borderline hemoglobin/hematocrit is accompanied by:

• Splenomegaly with thrombocytosis or leukocytosis 4
• Portal vein thrombosis or other unusual thrombotic events 4
• Isolated thrombocytosis, leukocytosis, or splenomegaly 4
• Aquagenic pruritus or erythromelalgia 1
• Documented sustained increase above individual baseline 5

Measurement Considerations:

• Hemoglobin is more reliable than hematocrit for monitoring because hematocrit can falsely increase by 2-4% with prolonged sample storage, while hemoglobin remains stable 2
• Hyperglycemia can falsely elevate hematocrit without affecting hemoglobin measurement 2
• Red cell mass measurement may be necessary in equivocal cases, particularly when plasma volume expansion is suspected 4

Diagnostic Algorithm for Variable Presentations

Step 1: Confirm Elevation

• Repeat measurements to document persistent elevation rather than transient changes 2
• Consider individual baseline values, not just population reference ranges 5

Step 2: Evaluate for Masked PV

• If hemoglobin/hematocrit are borderline but JAK2 mutation is positive with characteristic clinical features, proceed with bone marrow biopsy 1
• Bone marrow histology showing hypercellularity with trilineage growth (panmyelosis) supports diagnosis even with lower hemoglobin values 1

Step 3: Account for Confounding Factors

• Assess iron status (serum ferritin, transferrin saturation) as iron deficiency can mask true polycythemia 2
• Evaluate hydration status as dehydration can falsely elevate hematocrit 2
• Consider plasma volume expansion in patients with splenomegaly or other features suggesting masked PV 4

Common Pitfalls to Avoid

• Do not dismiss PV diagnosis solely because hemoglobin/hematocrit fall below WHO thresholds if JAK2 mutation is positive and clinical features are present 3
• Do not rely on a single measurement as values fluctuate with hydration, treatment, and iron status 2
• Do not overlook iron deficiency as a confounding factor that can simultaneously exist with erythrocytosis 2
• Do not use standard PV diagnostic thresholds at high altitude without adjustment, as physiologic adaptation can increase hemoglobin by 0.2-4.5 g/dL depending on elevation 2
• Do not perform red cell mass measurement when hematocrit exceeds 60% in the absence of obvious hemoconcentration, as this is costly redundancy 1