What does it mean if red blood cell (RBC) count is elevated and hematocrit is high?

Elevated Red Blood Cell Count and Hematocrit: Causes and Clinical Significance

Elevated red blood cell count and hematocrit indicate either polycythemia vera (a myeloproliferative neoplasm) or secondary polycythemia (due to increased erythropoietin production), both of which require prompt evaluation due to increased thrombotic risk. 1

Differential Diagnosis

Primary Polycythemia (Polycythemia Vera)

• Chronic myeloproliferative disorder characterized by clonal erythrocytosis
• Often involves other blood cell lines (leukocytosis, thrombocytosis)
• Associated with JAK2 mutation in most cases
• Increased risk of thrombotic events and mortality if untreated 2, 1

Secondary Polycythemia

• Caused by increased erythropoietin production due to:
  • Chronic hypoxia (COPD, sleep apnea)
  • Cyanotic heart disease
  • High altitude exposure
  • Smoking
  • Renal disease (renal cell carcinoma, renal cysts)
  • Androgen use
  • Certain genetic mutations affecting oxygen sensing pathways 1, 3

Diagnostic Approach

1. Initial Assessment:

   • Complete blood count with peripheral blood smear
   • Serum erythropoietin level (key differentiating test)
     • Low: suggests primary polycythemia
     • Normal/elevated: suggests secondary polycythemia 1, 4
   • JAK2 V617F mutation testing (positive in ~95% of PV cases) 1

2. Additional Testing Based on Initial Results:

   • Bone marrow aspirate and biopsy (if JAK2 positive or high clinical suspicion)
   • Arterial blood gas analysis (to assess hypoxemia)
   • Chest imaging (to evaluate for pulmonary causes)
   • Abdominal imaging (to evaluate for renal tumors, hepatic disorders)
   • Sleep study (if sleep apnea suspected)
   • Genetic testing for congenital causes in younger patients or those with family history 1, 4

Clinical Significance and Complications

• Thrombotic Risk: Elevated hematocrit increases blood viscosity, significantly increasing risk of both arterial and venous thrombosis 2
• Cerebrovascular Effects: Increased hematocrit is associated with decreased cerebral blood flow 2
• Microvascular Disturbances: Symptoms like erythromelalgia (burning pain in extremities) may occur 2, 1
• Disease Progression: In polycythemia vera, risk of progression to myelofibrosis or acute leukemia 1

Management Considerations

• Polycythemia Vera:

  • Therapeutic phlebotomy to maintain hematocrit <45%
  • Low-dose aspirin (81-100 mg daily) unless contraindicated
  • Cytoreductive therapy (hydroxyurea, interferon-α, ruxolitinib) for high-risk patients 1

• Secondary Polycythemia:

  • Address underlying cause when possible
  • Judicious phlebotomy for symptomatic patients (target hematocrit 55-60% for COPD or cyanotic heart disease)
  • Caution: overzealous phlebotomy in secondary polycythemia can increase stroke risk 1

Important Clinical Pitfalls

• Relative Polycythemia: Elevated hematocrit due to plasma volume contraction (dehydration) rather than increased red cell mass - requires volume repletion, not treatment for polycythemia 4

• Iron Deficiency: Repeated phlebotomies without proper diagnosis can lead to iron deficiency, decreased oxygen-carrying capacity, and paradoxically increased stroke risk 1

• Missed Diagnosis: Failure to distinguish between primary and secondary causes can lead to inappropriate management 4, 5

• Delayed Specialist Referral: Hematology consultation is recommended for confirmed polycythemia vera or when diagnosis remains unclear after initial evaluation 1, 6