What are the causes and treatments of a high hematocrit (Hct) level?

Causes and Treatment of High Hematocrit

High hematocrit levels can be caused by primary polycythemia vera, secondary erythrocytosis due to hypoxemia, or relative polycythemia from reduced plasma volume, with treatment requiring proper identification of the underlying cause and risk stratification to guide management decisions.

Primary Causes of High Hematocrit

Polycythemia Vera (PV)

• A myeloproliferative neoplasm characterized by:
  • JAK2 mutation (most commonly V617F)
  • Increased red blood cell mass
  • Often accompanied by elevated white blood cell count and/or thrombocytosis
  • Splenomegaly in many cases
  • Symptoms may include aquagenic pruritus and erythromelalgia 1
  • Iron deficiency is common at presentation or during disease course 2

Secondary Erythrocytosis

• Physiological increase in red blood cell mass in response to hypoxemia 3
• Common causes include:
  • Chronic lung disease
  • Congenital heart disease with right-to-left shunting
  • Sleep apnea
  • High altitude residence
  • Smoking (most frequent cause of increased hematocrit) 1
  • Methemoglobinemia (impairs oxygen delivery) 3

Relative Polycythemia

• Normal red cell mass with reduced plasma volume 1
• Causes include:
  • Dehydration
  • Stress polycythemia (Gaisböck syndrome)
  • Diuretic use

Diagnosis Approach

1. Initial evaluation:

   • Complete blood count with differential
   • Chest X-ray
   • Oxygen saturation measurement
   • Smoking history 1

2. Additional testing based on clinical suspicion:

   • JAK2 mutation testing for suspected PV
   • Arterial blood gas analysis for hypoxemia
   • Sleep study for suspected sleep apnea
   • Echocardiogram for cardiac evaluation

3. Definitive diagnosis:

   • Red blood cell mass and plasma volume measurements are required to differentiate between primary, secondary, and relative polycythemia 4
   • Male patients with hematocrit >60% and female patients with hematocrit >55% always have absolute polycythemia 1

Treatment Approaches

Polycythemia Vera Management

1. Risk stratification:

   • Low-risk: Age <60 years and no history of thrombosis
   • High-risk: Age ≥60 years or history of thrombosis 5

2. Core treatments:

   • Phlebotomy to maintain hematocrit <45%
   • Low-dose aspirin (81-100 mg daily) unless contraindicated 5

3. Cytoreductive therapy for high-risk patients:

   • Hydroxyurea (first-line in older patients)
   • Interferon-α (preferred in younger patients and women of childbearing age) 5

4. Monitoring:

   • Complete blood count every 3-6 months
   • Assessment of symptoms and complications 5

Secondary Erythrocytosis Management

1. Treatment of underlying cause when possible:

   • Oxygen therapy for hypoxemia
   • CPAP for sleep apnea
   • Smoking cessation 1

2. For congenital heart disease with right-to-left shunting:

   • The patient's own homeostatic processes generally direct achievement of an optimal level of red cell mass
   • Iron deficiency should be assessed and treated if present, as it can compromise oxygen transport without lowering viscosity 3
   • Phlebotomy is rarely necessary and routine phlebotomy is not supported by data 3
   • Phlebotomy (with equal volume fluid replacement) may be considered in special cases when:
     • After adequate hydration, hematocrit remains higher than patient's baseline
     • Symptoms persist
     • Evidence of end-organ damage attributable to hyperviscosity exists 3

3. For methemoglobinemia:

   • Avoid precipitating factors
   • For symptomatic patients with high methemoglobin levels:
     • Intravenous methylene blue (1-2 mg/kg)
     • Ascorbic acid as adjunctive therapy 3

Relative Polycythemia Management

• Hydration
• Address underlying causes (stress, diuretic use)

Special Considerations

1. Iron deficiency:

   • Common in PV patients and can exacerbate symptoms 2
   • In secondary erythrocytosis, iron deficiency should be treated as it can compromise oxygen transport 3
   • Assess serum iron, ferritin, and transferrin levels (mean corpuscular volume is not a reliable screening test) 3

2. Hyperviscosity:

   • Can lead to neurological manifestations, increased bleeding risk, and thrombotic complications 6
   • First-line therapy is rehydration (oral or intravenous) 3
   • No clear correlation between viscosity and measured hematocrit 3

3. Surgical considerations:

   • Elective surgery has increased risk in patients with pulmonary hypertension and high hematocrit 3
   • Epidural anesthesia may be better tolerated than general anesthesia 3
   • Anticoagulant treatment should be interrupted for the shortest possible time 3

4. Monitoring recommendations:

   • Regular hematocrit measurements
   • Clinical assessment for symptoms of hyperviscosity
   • Aggressive management of cardiovascular risk factors 5

Treatment Outcomes

With proper management, median survival in PV is approximately 14-27 years, with younger patients potentially achieving survival of 35-37 years 5. Maintaining hematocrit <45% significantly reduces the risk of thrombotic events 6, 7.