Management of Persistently Elevated Red Blood Cell Count
Patients with persistently elevated red blood cell counts should undergo immediate evaluation for polycythemia vera and other myeloproliferative disorders, with therapeutic phlebotomy indicated for symptomatic patients with hematocrit >65% to reduce the risk of thrombotic events. 1
Initial Assessment and Diagnostic Workup
When encountering a patient with persistently elevated RBC count, the following evaluations should be performed:
- Complete blood count with differential to assess all cell lines
- Peripheral blood smear examination
- Reticulocyte count
- Serum erythropoietin level
- JAK2 V617F mutation testing (and exon 12 if V617F negative but high clinical suspicion)
- Bone marrow biopsy if myeloproliferative neoplasm suspected
- Arterial blood gas to evaluate oxygen saturation
- Abdominal ultrasound to assess spleen size
- Review of medications that may cause erythrocytosis
Risk Stratification
Risk stratification is crucial for determining management approach:
- High risk: Age >60 years and/or history of thrombosis
- Low risk: Age <60 years and no history of thrombosis
Additional risk factors to consider:
- Leukocytosis (WBC >11 × 10^9/L) - independently associated with thrombotic events 2
- Cardiovascular risk factors (hypertension, smoking, diabetes)
- Symptoms of hyperviscosity
Management Strategies
1. Therapeutic Phlebotomy
- Indication: Symptomatic patients with hematocrit >65% 1
- Target: Maintain hematocrit <45% in men and women 2
- Procedure: Remove 250-500 mL of blood per session
- Frequency: Initially may be weekly, then adjust based on response
- Caution: Avoid aggressive phlebotomy which can lead to iron deficiency 1
2. Cytoreductive Therapy
For high-risk patients or those with poor tolerance of phlebotomy:
- First-line: Hydroxyurea (starting dose 15-20 mg/kg/day, adjust to maintain target blood counts) 1, 3
- Alternative options for hydroxyurea-resistant/intolerant cases:
- Ruxolitinib (JAK1/2 inhibitor)
- Interferon-alpha (particularly in younger patients)
3. Adjunctive Therapies
- Low-dose aspirin (81-100 mg daily) for thromboprophylaxis unless contraindicated
- Aggressive hydration (2.5-3 L/m²/day) unless contraindicated by renal insufficiency 1
- Iron supplementation only if documented iron deficiency, with careful monitoring of hemoglobin 1
Monitoring and Follow-up
- Weekly blood counts during initial treatment phase
- Once stabilized, monitor CBC every 2-3 months
- Regular assessment for symptoms of hyperviscosity
- Evaluate for disease progression (fibrotic transformation or leukemic evolution)
- Monitor for treatment-related adverse effects
Complications to Watch For
- Thrombotic events: Both arterial and venous thrombosis
- Hyperviscosity symptoms: Headache, visual disturbances, fatigue, dizziness
- Bleeding complications: Due to acquired von Willebrand syndrome or platelet dysfunction
- Tumor lysis syndrome: With rapid cytoreduction
- Secondary iron deficiency: From repeated phlebotomies
Special Considerations
- In patients with polycythemia vera, controlling both hematocrit (≤45%) and WBC count (<11 × 10^9/L) is important for reducing thrombotic risk 2
- For patients with secondary erythrocytosis (e.g., from chronic hypoxemia), treat the underlying cause rather than focusing solely on the elevated RBC count
- Avoid routine phlebotomies without clear indication due to risk of iron depletion and stroke 1
By following this structured approach to evaluation and management, the risk of thrombotic complications from persistently elevated RBC counts can be significantly reduced, improving patient outcomes and quality of life.