Hemoglobin and Hematocrit Parameters for Therapeutic Phlebotomy
For polycythemia vera, maintain hematocrit strictly below 45% through therapeutic phlebotomy, with consideration for a lower target of approximately 42% in women and African Americans. 1, 2
Target Parameters by Condition
Polycythemia Vera (Primary Indication)
Hematocrit target: <45% for all patients 1, 2
- This target is based on the landmark CYTO-PV trial, which demonstrated that maintaining hematocrit <45% versus 45-50% significantly reduced cardiovascular death and major thrombotic events (2.7% vs 9.8%, P=0.007) 1
- Women and African Americans: Consider target of approximately 42% due to physiological differences in baseline hematocrit values 2, 3
Hemoglobin thresholds for diagnosis (not treatment targets):
Hemochromatosis
- Target ferritin: 50-100 μg/L (not hematocrit-based) 1
- Perform weekly phlebotomy (500 mL blood removal) as tolerated 1
- Check hematocrit/hemoglobin prior to each phlebotomy 1
- Allow hematocrit/hemoglobin to fall by no more than 20% of prior level 1
- Continue maintenance phlebotomy to keep ferritin between 50-100 μg/L 1
Secondary Polycythemia (Cyanotic Heart Disease, Chronic Hypoxia)
- Therapeutic phlebotomy indicated ONLY when:
- Critical warning: Repeated routine phlebotomies are contraindicated in secondary polycythemia due to risk of iron depletion, decreased oxygen-carrying capacity, and stroke 3, 5
Practical Implementation Algorithm
For Polycythemia Vera Patients
Initial Phase:
- Perform phlebotomy weekly or biweekly (500 mL per session) until hematocrit <45% is achieved 1, 2
- Check hematocrit before each phlebotomy session 1, 3
- Provide adequate fluid replacement (equal volume of saline or dextrose) to prevent hypotension and hemoconcentration 3
Maintenance Phase:
- Monitor hematocrit every 3-6 months in stable patients 2
- Perform phlebotomy as needed to maintain hematocrit <45% 1
- Red flag: If patient requires ≥3 phlebotomies per year despite hydroxyurea therapy (≥2 g/day for 3 months), this indicates hydroxyurea resistance and significantly increased thrombotic risk (20.5% vs 5.3% at 3 years, P<0.0001) 6
Adjunctive Therapy (All PV Patients):
- Low-dose aspirin 81-100 mg daily (unless contraindicated) 1, 2
- Cytoreductive therapy (hydroxyurea or interferon-α) for high-risk patients (age >60 years or prior thrombosis) 1, 2
Critical Safety Considerations
Avoid These Common Pitfalls:
- Never accept hematocrit targets of 45-50% in polycythemia vera—the CYTO-PV trial definitively showed increased thrombotic risk at these levels 2
- Never perform phlebotomy without adequate volume replacement, especially in elderly patients with cardiovascular disease, as this can precipitate dangerous hypotension 2, 3
- Never perform routine repeated phlebotomies in secondary polycythemia (except when Hb >20 g/dL, Hct >65%, with hyperviscosity symptoms) due to stroke risk from iron depletion 3, 5
- Never allow hematocrit/hemoglobin to fall >20% from baseline during hemochromatosis treatment 1
Special Population Considerations:
- Elderly patients with cardiovascular disease: Require particularly careful fluid replacement during phlebotomy 2, 3
- Pregnant patients with PV: Use interferon-α (not hydroxyurea) if cytoreduction needed; continue phlebotomy to maintain Hct <45% 2
- Patients with iron deficiency and erythrocytosis: Cautious iron supplementation with close hemoglobin monitoring is necessary, as rapid increases in red cell mass can occur 5
Monitoring Parameters
Before Each Phlebotomy:
During Treatment:
- Hematocrit levels every 3-6 months (PV patients) 2
- Serum ferritin every 10-12 phlebotomies (hemochromatosis patients) 1
- Monitor for new thrombosis, bleeding, or disease progression 1, 2
Treatment Failure Indicators: