Can polycythemia vera cause fatigue?

Fatigue in Polycythemia Vera

Yes, polycythemia vera commonly causes fatigue, which is one of the most prevalent symptoms affecting patients' quality of life. 1

Pathophysiology of Fatigue in Polycythemia Vera

Fatigue in polycythemia vera (PV) occurs through several mechanisms:

1. Increased Blood Viscosity:

   • The elevated red blood cell mass increases blood viscosity, particularly at low shear rates 2
   • This leads to decreased blood flow and impaired tissue oxygenation despite the increased number of red blood cells
   • The relationship between hematocrit and oxygen transport is complex - higher hematocrit doesn't necessarily improve tissue oxygenation 2

2. Microcirculatory Disturbances:

   • Abnormal blood flow dynamics in small vessels
   • Endothelial displacement of platelets and leukocytes
   • Decreased flow rates in small vessels 2

3. Pro-inflammatory State:

   • PV is characterized by excessive production of pro-inflammatory cytokines 3
   • Chronic inflammation contributes to persistent fatigue

4. Metabolic Burden:

   • The body expends additional energy maintaining the increased cell mass
   • This creates a metabolic burden that manifests as fatigue

Clinical Presentation and Diagnosis

Fatigue in PV patients presents as:

• Persistent tiredness disproportionate to activity level
• Reduced exercise tolerance
• Often accompanied by other PV symptoms including:
  • Pruritus (33% of patients) 4
  • Erythromelalgia (5.3%) 4
  • Visual disturbances (14%) 4
  • Abdominal discomfort from splenomegaly (36%) 4

When evaluating fatigue in a patient with suspected PV:

• Look for elevated hemoglobin (>16.5 g/dL in men, >16.0 g/dL in women) 4
• Check for JAK2 mutation (present in >95% of PV cases) 4
• Measure serum erythropoietin (typically low in PV) 5
• Consider bone marrow examination to confirm diagnosis 5

Management of PV-Related Fatigue

Management focuses on treating the underlying PV to improve fatigue:

1. Phlebotomy:

   • First-line therapy to reduce blood viscosity
   • Target hematocrit <45% to reduce thrombotic events and improve symptoms 4, 6
   • May provide rapid relief of fatigue symptoms

2. Cytoreductive Therapy:

   • Indicated for high-risk patients (age ≥60 years or history of thrombosis)
   • Also beneficial for persistent symptoms including fatigue 4
   • Options include:
     • Hydroxyurea (first-line cytoreductive agent)
     • Interferon-alpha (particularly in younger patients)
     • Ruxolitinib (JAK inhibitor) for patients intolerant or resistant to hydroxyurea 7

3. Aspirin Therapy:

   • Low-dose aspirin recommended for all PV patients without contraindications 4
   • Improves microcirculation which may help reduce fatigue

Important Considerations

• Differential Diagnosis: Rule out other causes of fatigue (anemia, sleep disorders, depression, hypothyroidism)
• Monitoring: Regular follow-up to assess symptom burden and disease progression
• Disease Progression: Be aware that increasing fatigue may signal disease progression to myelofibrosis (occurs in 12.7% of PV patients) 4
• Cardiovascular Risk: Address modifiable cardiovascular risk factors (smoking, hypertension, dyslipidemia) which can worsen symptoms 3

Pitfalls to Avoid

1. Attributing all fatigue to PV: Consider concurrent conditions that may contribute to fatigue
2. Inadequate hematocrit control: Failure to maintain hematocrit <45% leads to persistent symptoms
3. Overlooking disease progression: Worsening fatigue may indicate transformation to myelofibrosis or acute myeloid leukemia
4. Ignoring quality of life: Fatigue significantly impacts daily functioning and should be actively addressed even when hematologic parameters are controlled

By addressing the underlying disease mechanisms through appropriate treatment, most patients with PV-related fatigue can experience significant symptom improvement.