What does it mean if a patient has a high hematocrit (Hct) and a high white blood cell (WBC) count?

High Hematocrit and High White Blood Cell Count: Clinical Significance

An elevated hematocrit combined with an elevated white blood cell count most commonly indicates polycythemia vera (PV), a myeloproliferative neoplasm that significantly increases thrombotic risk and requires immediate evaluation and management to prevent life-threatening complications.

Primary Differential Diagnosis

Polycythemia Vera (Most Likely)

The combination of elevated hematocrit and elevated WBC count strongly suggests PV, particularly when WBC exceeds 10 × 10⁹/L 1. This represents a clonal myeloproliferative disorder with serious implications:

• Thrombotic risk increases dramatically with both elevated hematocrit and WBC count acting as independent risk factors 1, 2
• Approximately half of PV patients display either thrombocytosis or leukocytosis 1
• Elevated WBC count >11 × 10⁹/L increases thrombotic event risk by 2.35-fold (HR 2.35; 95% CI 1.598-3.465) 2
• Hematocrit >45% increases thrombotic risk by 1.84-fold (HR 1.84; 95% CI 1.234-2.749) 2

Secondary Polycythemia

Consider secondary causes when clinical features don't fit PV 3:

• Chronic hypoxemia from pulmonary disease
• Smoking (most frequent cause of elevated hematocrit) 3
• High-altitude exposure
• Renal tumors or cysts producing erythropoietin

Acute Conditions

• Infection with hemoconcentration - bacterial infections can cause both leukocytosis and relative polycythemia from dehydration 4
• Stress response - surgery, trauma, or emotional stress can double WBC count within hours 4

Critical Clinical Features to Assess

Symptoms Suggesting PV (High Specificity)

• Splenomegaly - highly indicative of PV 3
• Aquagenic pruritus (itching after water exposure) - specific for PV 3
• Erythromelalgia (burning pain in extremities) - associated with PV 1, 3

Symptoms Suggesting Secondary Polycythemia

• Dyspnea and signs of pulmonary disease 3
• Chronic hypoxemia symptoms

Red Flags for Malignancy

• Fever, unexplained weight loss, bruising, or fatigue 4
• Progressive symptoms without clear secondary cause

Diagnostic Workup Algorithm

Initial Laboratory Assessment

1. Repeat complete blood count with peripheral smear 4

   • Verify hematocrit and WBC elevation
   • Assess cell morphology and maturity
   • Look for toxic granulations or abnormal cells

2. Specific thresholds indicating absolute polycythemia 3:

   • Males: hematocrit >60% always indicates absolute polycythemia
   • Females: hematocrit >55% always indicates absolute polycythemia

3. Additional markers for PV 1, 3:

   • Platelet count (thrombocytosis supports PV diagnosis)
   • JAK2 mutation testing (diagnostic for PV)
   • Serum erythropoietin level (low in PV, high in secondary)

When Blood Volume Studies Are Needed

• NOT needed if 3:

  • Male hematocrit >60% or female >55% (absolute polycythemia confirmed)
  • Splenomegaly present with elevated counts
  • Obvious pulmonary disease present
  • Patient is a smoker (advise smoking cessation first)

• Consider blood volume studies if 3:

  • Hematocrit elevated but below absolute thresholds
  • No clinical or biological signs suggesting specific etiology
  • Need to distinguish true polycythemia from relative polycythemia

Immediate Management Priorities

Thrombotic Risk Reduction

Both hematocrit and WBC count must be controlled to prevent thrombotic events 2:

1. Target hematocrit <45% through phlebotomy 1, 2

   • May need lower targets (42% for women) in specific situations 1
   • Phlebotomy reduces but does not eliminate thrombotic risk 1

2. Control elevated WBC count 1, 2:

   • Even when hematocrit is controlled at ≤45%, WBC >12 × 10⁹/L significantly increases thrombotic risk (HR 1.95; 95% CI 1.066-3.554) 2
   • Hydroxyurea (2 g/day) for cytoreduction if WBC remains elevated 1

3. Aspirin therapy (81-100 mg/day) for all PV patients unless contraindicated 1

Risk Stratification for PV

Low-risk patients (no history of thrombosis, age <60 years) 1:

• Aspirin and phlebotomy only
• Target hematocrit <45%

High-risk patients (history of thrombosis OR age ≥60 years) 1:

• Aspirin, phlebotomy, AND cytoreductive therapy
• Hydroxyurea as first-line cytoreductive agent
• Target hematocrit <45% and WBC control

Critical Pitfalls to Avoid

1. Do not ignore elevated WBC count - it is an independent thrombotic risk factor even when hematocrit is controlled 2

2. Do not perform repeated routine phlebotomies without monitoring - risk of iron depletion, decreased oxygen-carrying capacity, and paradoxically increased stroke risk 1

3. Serial hematocrit measurements are essential - initial normal values may mask early bleeding or evolving conditions 1

4. Smoking cessation is mandatory before extensive workup in smokers with elevated hematocrit 3

5. Refer to hematology/oncology if malignancy cannot be excluded or if no clear secondary cause is identified 4

Special Considerations

Hyperleukocytosis (WBC >100 × 10⁹/L)

If WBC count is extremely elevated 5:

• Aggressive IV hydration (2.5-3 liters/m²/day)
• Monitor for tumor lysis syndrome
• Consider hydroxyurea (50-60 mg/kg/day) for rapid cytoreduction
• Avoid leukapheresis in APL due to fatal hemorrhage risk 1, 5

Monitoring During Treatment

• Serial hematocrit and WBC measurements to assess response 1
• Coefficient of variation for hemoglobin is superior to hematocrit for monitoring 1
• Monitor for iron deficiency if repeated phlebotomy required 1