What hematocrit target should be aimed for when performing therapeutic phlebotomy in patients with polycythemia vera or other causes of elevated red‑cell mass?

Hematocrit Target for Therapeutic Phlebotomy in Polycythemia Vera

Maintain hematocrit strictly below 45% through therapeutic phlebotomy in all patients with polycythemia vera, with a target of approximately 42% for women and African Americans. 1

Evidence-Based Hematocrit Threshold

The CYTO-PV randomized controlled trial definitively established that maintaining hematocrit <45% reduces the combined endpoint of cardiovascular death and major thrombosis to 2.7% compared with 9.8% when hematocrit is maintained at 45-50% (hazard ratio 3.91; 95% CI 1.45-10.53; P=0.007). 2 This represents the highest-quality evidence available and forms the foundation of current guideline recommendations. 1

• The 45% threshold applies universally to all polycythemia vera patients regardless of age or risk category. 1
• Do not accept hematocrit targets of 45-50%, as the CYTO-PV trial definitively showed increased thrombotic risk at these levels. 1

Sex and Race-Specific Adjustments

Women and African Americans should target hematocrit ≈42% due to physiological differences in baseline hematocrit values. 1, 3

• These populations have naturally lower baseline hematocrit levels, making the standard 45% threshold potentially too permissive. 1
• The lower target accounts for sex-related hormonal differences and racial variations in normal hematocrit ranges. 1

Phlebotomy Procedure and Safety

When performing therapeutic phlebotomy, remove approximately 300-450 mL of blood per session with careful hemodynamic monitoring. 3

Critical safety requirement: Phlebotomy must be performed with equal-volume fluid replacement (normal saline or dextrose) to prevent hemoconcentration and hypotension. 1, 3

• Inadequate fluid replacement can precipitate dangerous hypotension, particularly in elderly patients with cardiovascular disease. 1
• Never perform phlebotomy without volume replacement, as this paradoxically increases hemoconcentration and stroke risk. 3

Clinical Outcomes with Proper Hematocrit Control

Aggressive phlebotomy to maintain hematocrit <45% has dramatically improved survival in polycythemia vera:

• Median survival has increased from <4 years** historically (with inadequate phlebotomy) to **>10 years with modern aggressive phlebotomy protocols. 1
• Contemporary data show median survival of 14-28 years, with patients aged ≤40 years achieving survival exceeding 35 years. 4

Monitoring Frequency

• Hematocrit levels should be monitored every 3-6 months in stable patients on adequate therapy. 1
• More frequent monitoring is required during initial phlebotomy induction or when adjusting cytoreductive therapy. 1

When Phlebotomy Alone Is Insufficient

Hydroxyurea resistance/intolerance is defined by: the need for phlebotomy to maintain hematocrit <45% after 3 months of at least 2 g/day hydroxyurea. 1

• This indicates inadequate disease control and necessitates escalation to second-line cytoreductive therapy (interferon-α or ruxolitinib). 1
• Frequent phlebotomy requirements (inability to maintain target without repeated procedures) signal the need for cytoreductive therapy initiation or intensification. 1

Common Pitfalls to Avoid

• Never target hematocrit 45-50% – this range is associated with significantly increased thrombotic events. 1
• Never perform phlebotomy without volume replacement – this increases stroke risk through hemoconcentration. 1, 3
• Do not overlook iron deficiency – iron-deficient red cells have reduced oxygen-carrying capacity and deformability, paradoxically increasing stroke risk despite lower hemoglobin. 3
• Avoid using MCV alone to screen for iron deficiency in erythrocytosis – serum ferritin and transferrin saturation are required for accurate diagnosis. 3

Adjunctive Therapy

All patients with polycythemia vera should receive low-dose aspirin 81-100 mg daily (unless contraindicated) in addition to phlebotomy, as this significantly reduces cardiovascular death, myocardial infarction, stroke, and venous thromboembolism. 1, 5