What does a high hematocrit (Hct) level with all other Complete Blood Count (CBC) parameters normal indicate?

Elevated Hematocrit with Normal Other CBC Parameters

An isolated elevated hematocrit with otherwise normal CBC parameters most commonly indicates relative polycythemia due to dehydration or hemoconcentration, but may also be an early sign of polycythemia vera requiring further evaluation. 1

Causes of Isolated Elevated Hematocrit

Primary Causes:

• Polycythemia vera (PV): A myeloproliferative neoplasm characterized by unregulated red blood cell production 2
  • Early PV may present with isolated hematocrit elevation before other CBC parameters become abnormal
  • Requires JAK2 mutation testing for diagnosis

Secondary Causes:

• Relative polycythemia (pseudopolycythemia): Most common cause

  • Dehydration/hemoconcentration
  • Diuretic use
  • Gastrointestinal fluid losses
  • Excessive vomiting or diarrhea
  • Burns
  • Severe dehydration

• True secondary polycythemia:

  • Chronic hypoxic conditions (COPD, sleep apnea, high altitude)
  • Smoking
  • Renal disease (renal cell carcinoma, polycystic kidney disease)
  • Inappropriate erythropoietin production

Clinical Significance and Risks

An elevated hematocrit increases thrombotic risk:

• In polycythemia vera, hematocrit values ≥45% are associated with significantly higher thrombotic risk 2
• The CYTO-PV trial demonstrated that maintaining hematocrit <45% reduced the risk of cardiovascular death and major thrombotic events 2
• Even in the general population, each 5% increment in hematocrit increases venous thromboembolism risk by 25% 3

Diagnostic Approach

1. Confirm true elevation:

   • Repeat CBC to rule out lab error
   • Check hydration status
   • Obtain sample when patient is well-hydrated

2. If elevation persists:

   • Check erythropoietin level
   • Consider JAK2 mutation testing (V617F and exon 12)
   • Evaluate for secondary causes (oxygen saturation, sleep study if indicated)
   • Consider red cell mass measurement in unclear cases

Management Based on Cause

If dehydration/relative polycythemia:

• Rehydration
• Address underlying cause of fluid loss
• Monitor hematocrit until normalized

If polycythemia vera is diagnosed:

• Risk stratification:

  • Low-risk: Age <60 years, no prior thrombosis
  • High-risk: Age ≥60 years and/or prior thrombosis

• Treatment:

  • All patients: Target hematocrit <45% 2
  • Low-risk PV: Aspirin plus phlebotomy 2
  • High-risk PV: Aspirin, phlebotomy, plus cytoreductive therapy (hydroxyurea first-line) 2
  • Hydroxyurea-resistant/intolerant: Consider ruxolitinib (achieves hematocrit control in ~88% of patients) 4

If secondary polycythemia:

• Treat underlying cause
• Consider phlebotomy if symptomatic or hematocrit >54% in men or >52% in women

Monitoring and Follow-up

• Regular CBC monitoring (frequency depends on cause and severity)
• For PV patients: Monitor for thrombotic events, disease progression, and treatment response
• For secondary causes: Address underlying condition and monitor resolution

Pitfalls to Avoid

1. Misinterpreting relative polycythemia: Always assess hydration status before extensive workup
2. Overlooking early PV: Normal WBC and platelet counts don't rule out early PV
3. Inadequate hematocrit control: Real-world data shows 54-64% of PV patients have hematocrit >50% at times 5
4. Overreliance on hematocrit alone: Consider hemoglobin measurement which is more stable with sample storage 1
5. Ignoring thrombotic risk: Even mild elevations increase risk, especially in those with other risk factors 6