How is a high hematocrit (elevated red blood cell count) treated?

Treatment of High Hematocrit (Elevated Red Blood Cell Count)

Phlebotomy is the primary treatment for high hematocrit, with a target of maintaining hematocrit below 45% in most patients with polycythemia vera or other causes of elevated red blood cell count. 1, 2

Risk Assessment and Initial Management

Determining the Cause

• Evaluate for primary causes (polycythemia vera) versus secondary causes (hypoxia, smoking, high altitude, cyanotic heart disease)
• Initial workup should include:
  • Complete blood count with differential
  • Iron studies
  • Serum erythropoietin level
  • JAK2 V617F mutation testing 2

Risk Stratification for Polycythemia Vera

• Low risk: Age <60 years with no history of thrombosis
• High risk: Age ≥60 years or prior history of thrombosis 2

Treatment Algorithm

First-Line Treatment

1. Therapeutic Phlebotomy

   • Target hematocrit <45% for men and <42% for women 2
   • Phlebotomy regimen: 300-450 ml of blood withdrawn weekly or twice weekly until target hematocrit is reached 1
   • Maintenance phase: Same blood volume removed per phlebotomy as induction phase, with intervals determined by hematocrit levels 1

2. Low-dose Aspirin

   • Add 81-100 mg daily for all patients without contraindications 2
   • Reduces risk of thrombotic complications 1

Additional Treatments for High-Risk Patients

For patients who are:

• Age >60 years
• Have previous thrombotic events
• Poor tolerance to phlebotomy
• Require frequent phlebotomies
• Have symptomatic/progressive splenomegaly
• Have severe disease-related symptoms
• Have platelet counts >1500 × 10^9/l
• Have leukocyte count >15 × 10^9/l 1, 2

Add cytoreductive therapy:

• First-line options:
  • Hydroxyurea
  • Recombinant interferon alpha (rIFNα) 1, 2
• Second-line options:
  • Ruxolitinib (for patients intolerant/resistant to hydroxyurea) 1
  • Busulfan (in select cases) 2

Special Considerations

Secondary Polycythemia

• For patients with secondary polycythemia (e.g., cyanotic congenital heart disease):
  • More conservative phlebotomy with target hematocrit of 60% may be reasonable 2
  • Aggressive phlebotomy should be avoided due to potential risk of stroke 1, 2
  • Treat underlying cause when possible 2

Iron Deficiency from Repeated Phlebotomy

• In case of documented severe tissue iron deficiency with symptoms (pica, mouth paresthesia, esophagitis, restless legs):
  • Iron supplementation is indicated 1
  • Monitor for hematocrit worsening with iron therapy, which may indicate need for cytoreduction 1

Cardiovascular Risk Management

• Aggressively manage all cardiovascular risk factors 1
• Monitor for thrombotic complications 2

Evidence Supporting Strict Hematocrit Control

The CYTO-PV trial demonstrated that maintaining hematocrit <45% significantly reduces cardiovascular death and major thrombotic events compared to less strict control (45-50%):

• Primary endpoint (death from cardiovascular causes or major thrombotic events) occurred in 2.7% of patients in the low-hematocrit group vs 9.8% in the high-hematocrit group
• Hazard ratio: 3.91 (95% CI 1.45-10.53) 1, 2

Monitoring

• Regular follow-up every 3-6 months with CBC and symptom assessment 2
• Monitor for:
  • Resolution of hyperviscosity symptoms
  • Thrombotic complications
  • Bleeding complications
  • Disease progression
  • Iron deficiency from repeated phlebotomies 2

Cautions and Pitfalls

• Avoid aggressive phlebotomy in secondary polycythemia, especially with cyanotic heart disease 1, 2
• Be aware that excessive phlebotomy can lead to iron deficiency, which may worsen symptoms
• Consider that optimal hematocrit may differ between healthy individuals and those with disease 3
• In patients with renal impairment, ensure adequate hydration when undergoing procedures involving contrast media 2

By maintaining strict hematocrit control through appropriate phlebotomy and, when indicated, cytoreductive therapy, the risk of thrombotic complications can be significantly reduced in patients with elevated red blood cell counts.