What is the target hematocrit (Hct) in secondary polycythemia?

Target Hematocrit in Secondary Polycythemia

The target hematocrit in secondary polycythemia should be maintained below 45% to reduce the risk of cardiovascular events and thrombosis. 1

Evidence Base and Rationale

The recommendation for maintaining hematocrit below 45% is strongly supported by high-quality evidence:

• The CYTO-PV trial, a landmark randomized clinical trial of 365 patients with polycythemia vera, demonstrated that maintaining hematocrit <45% resulted in a significantly lower rate of cardiovascular death and major thrombotic events compared to a target of 45-50% 2
• After a median follow-up of 31 months, the primary endpoint (cardiovascular death or major thrombotic events) occurred in only 2.7% of patients in the low-hematocrit group (<45%) compared to 9.8% in the high-hematocrit group (45-50%) 3, 2
• This represents a nearly 4-fold increased risk (hazard ratio 3.91) of adverse cardiovascular outcomes when hematocrit is maintained at higher levels 2

Management Approach for Secondary Polycythemia

Therapeutic Interventions

1. Phlebotomy:

   • First-line treatment to achieve and maintain hematocrit <45%
   • Frequency should be adjusted based on individual response
   • Patients requiring ≥3 phlebotomies per year despite other treatments may represent a higher-risk group 4

2. Cytoreductive Therapy (when indicated):

   • Consider in patients with:
     • Difficulty maintaining hematocrit <45% with phlebotomy alone
     • High thrombotic risk (age ≥60 years or history of thrombosis)
     • Progressive splenomegaly
     • Intolerance to phlebotomy
   • Hydroxyurea is the first-line cytoreductive agent 1, 5
   • Interferon-α is preferred for younger patients and women of childbearing age 1

3. Antiplatelet Therapy:

   • Low-dose aspirin (81-100 mg daily) unless contraindicated
   • Should be withheld if platelet count exceeds 1,500 × 10^9/L due to bleeding risk 1

Monitoring

• Complete blood count every 3-6 months
• Regular assessment for symptoms of hyperviscosity
• Surveillance for disease progression or complications 1

Special Considerations

Testosterone-Induced Secondary Polycythemia

For patients with testosterone-induced secondary polycythemia, the same target hematocrit of <45% applies, with management options including:

• Reducing testosterone dosage
• Switching to a transdermal formulation (which has lower risk of polycythemia)
• Implementing therapeutic phlebotomy when necessary 1

Secondary Polycythemia Due to Chronic Hypoxia

In patients with chronic hypoxia (e.g., cyanotic congenital heart disease):

• The approach differs slightly as erythrocytosis is a compensatory mechanism
• Iron status should be monitored, as iron deficiency can worsen symptoms despite high hematocrit
• Phlebotomy with concurrent iron therapy may be appropriate in selected cases 6, 7
• Dehydration should be avoided as it can precipitate hyperviscosity symptoms 7

Risks of Inadequate Management

Failure to maintain hematocrit below 45% is associated with:

• Increased risk of thrombotic events
• Higher cardiovascular mortality
• Symptoms of hyperviscosity including headache, dizziness, and visual disturbances 3, 2

Patients requiring frequent phlebotomies (≥3 per year) while on hydroxyurea have been shown to have a significantly higher thrombosis rate (20.5% vs. 5.3% at 3 years) compared to those requiring fewer phlebotomies 4.