Hydroxyurea Dose Adjustment Based on Hematocrit
For polycythemia vera, maintain hematocrit below 45% through phlebotomy as the primary method, while using hydroxyurea at 15-20 mg/kg/day (or 2 g/day for patients ≤80 kg, 2.5 g/day for >80 kg) for cytoreduction—do not adjust hydroxyurea dose based on hematocrit alone, but rather monitor for treatment failure if hematocrit remains elevated despite adequate dosing and phlebotomy. 1, 2
Primary Treatment Strategy for Hematocrit Control
- Phlebotomy is the primary method for maintaining hematocrit <45%, not hydroxyurea dose adjustment 1
- Hydroxyurea serves as cytoreductive therapy to reduce phlebotomy requirements and control myeloproliferation, but the hematocrit target is achieved through phlebotomy 1
- The target hematocrit of <45% applies to both men and women, though individualization may be appropriate (e.g., 42% for women or patients with progressive vascular symptoms) 1
Hydroxyurea Dosing Protocol
Initial dosing:
- Start at 15-20 mg/kg/day (not the older 30 mg/kg/day loading dose, which causes excessive early cytopenia) 3
- Standard maintenance: 2 g/day for patients ≤80 kg, or 2.5 g/day for patients >80 kg 4, 2
- Assess response after at least 3 months at adequate doses 4, 2
Monitoring schedule:
- CBC with reticulocyte count every 2-4 weeks during dose titration 4
- Weekly CBC until stable dose achieved 4
- Every 1-3 months once on stable dose 4
Critical Thresholds Requiring Dose Reduction or Discontinuation
You must reduce or hold hydroxyurea if any of the following occur (these are based on cytopenias, not hematocrit elevation):
- Absolute neutrophil count <1.0 × 10⁹/L 4, 2
- Platelet count <100 × 10⁹/L 4, 2, 5
- Hemoglobin <10 g/dL 1, 4, 2
- Development of leg ulcers or mucocutaneous toxicity 1, 4
- Drug-induced fever 1, 4
Identifying Treatment Failure (Not Dose Adjustment)
If hematocrit remains elevated despite optimal management, this indicates treatment failure, not a need for dose escalation:
- Patients requiring ≥3 phlebotomies per year while on hydroxyurea have a 3.3-fold higher thrombosis risk and represent inadequate disease control 6
- Failure to achieve hematocrit <45% after 3 months at 2 g/day (or 2.5 g/day if >80 kg) defines hydroxyurea resistance 4, 2
- Do not escalate hydroxyurea beyond 2-2.5 g/day—instead, consider second-line therapy with ruxolitinib or interferon-alpha 4, 2
Common Pitfall to Avoid
The most critical error is attempting to control hematocrit solely through hydroxyurea dose escalation rather than using phlebotomy. In one study, patients on hydroxyurea who still required frequent phlebotomies actually received higher hydroxyurea doses but had worse outcomes, indicating that phlebotomy requirement reflects disease biology rather than inadequate hydroxyurea dosing 6. Additionally, excessive hematocrit elevation (>30% in sickle cell disease context) on hydroxyurea can paradoxically increase thrombotic risk through hyperviscosity 7.