Polycythemia Vera

Polycythemia vera (PV) is a rare, chronic blood cancer that causes the bone marrow to produce too many red blood cells. This overproduction leads to thickened blood, increasing the risk of dangerous blood clots and other complications. Affecting about 2 per 100,000 people, PV is part of a group of conditions called myeloproliferative neoplasms. While PV is a serious condition, with proper management, many people live normal lifespans and maintain good quality of life.

⚠️ Seek Immediate Medical Care

Call 911 for: chest pain, difficulty breathing, sudden weakness/numbness on one side, difficulty speaking, severe headache, vision changes, or signs of stroke/heart attack. PV increases risk of life-threatening blood clots. Also seek care for severe abdominal pain (possible splenic infarction).

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of any medical condition.

Understanding Polycythemia Vera

PV occurs when a mutation in blood stem cells causes uncontrolled production of blood cells, primarily red blood cells. The JAK2 gene mutation is found in about 95% of PV cases. This overproduction makes blood thicker and more prone to clotting.

Key Characteristics

  • Chronic myeloproliferative neoplasm
  • Excessive red blood cell production
  • Often increased white cells and platelets too
  • Blood becomes thick and viscous
  • Spleen often enlarged
  • Can transform to myelofibrosis or acute leukemia

Demographics

  • Average age at diagnosis: 60 years
  • Slightly more common in men
  • Rare before age 40
  • Very rare in children
  • Incidence: 0.7-2.6 per 100,000 annually
  • Not directly inherited but familial clustering occurs

Disease Phases

  • Pre-polycythemic phase:
    • Borderline blood counts
    • JAK2 mutation present
    • Some symptoms
  • Polycythemic phase:
    • Elevated red cell mass
    • Full symptom development
    • Thrombosis risk highest
  • Post-polycythemic phase:
    • Myelofibrosis (10-20%)
    • Acute leukemia (2-5%)

Signs and Symptoms

Many patients are diagnosed incidentally through routine blood work. When symptoms occur, they result from increased blood thickness and enlarged spleen.

Common Symptoms

  • Headaches (48%):
    • Often severe
    • Due to increased blood viscosity
    • May be throbbing
  • Aquagenic pruritus (40%):
    • Intense itching after warm bath/shower
    • Characteristic of PV
    • Can be severe and distressing
  • Fatigue (80%):
    • Often profound
    • Affects quality of life
    • May persist despite treatment
  • Dizziness/vertigo (50%):
    • Lightheadedness
    • Worse with position changes

Vascular Symptoms

  • Erythromelalgia:
    • Burning pain in hands/feet
    • Red or purple discoloration
    • Responds to aspirin
  • Visual disturbances:
    • Blurred vision
    • Blind spots
    • Flashing lights
  • Tinnitus: Ringing in ears
  • Paresthesias: Numbness, tingling

Physical Signs

  • Plethora:
    • Ruddy complexion
    • Red face and palms
    • Reddish-purple color
  • Splenomegaly (70%):
    • Enlarged spleen
    • Left upper quadrant fullness
    • Early satiety
  • Hepatomegaly (40%): Enlarged liver
  • Hypertension (30%): High blood pressure

Constitutional Symptoms

  • Night sweats
  • Weight loss (10%)
  • Fever
  • Bone pain
  • Abdominal discomfort

Thrombotic Events

20-40% present with or develop thrombosis:

  • Arterial thrombosis:
    • Stroke
    • Heart attack
    • Peripheral arterial occlusion
  • Venous thrombosis:
    • Deep vein thrombosis
    • Pulmonary embolism
    • Portal vein thrombosis
    • Budd-Chiari syndrome

Diagnosis

WHO Diagnostic Criteria (2016)

Diagnosis requires meeting all 3 major criteria OR first 2 major + minor criterion:

Major Criteria:

  1. Hemoglobin/Hematocrit:
    • Men: Hgb >16.5 g/dL or Hct >49%
    • Women: Hgb >16 g/dL or Hct >48%
    • Or increased red cell mass
  2. Bone marrow biopsy:
    • Hypercellularity
    • Trilineage proliferation
    • Pleomorphic megakaryocytes
  3. JAK2 mutation:
    • JAK2 V617F (95% of cases)
    • JAK2 exon 12 (3-5% of cases)

Minor Criterion:

  • Subnormal serum erythropoietin level

Laboratory Tests

  • Complete blood count:
    • Elevated hemoglobin/hematocrit
    • Often elevated WBC (>11,000)
    • Often elevated platelets (>400,000)
  • JAK2 mutation testing:
    • Essential for diagnosis
    • V617F most common
    • Quantitative testing available
  • Erythropoietin level:
    • Low or low-normal
    • Helps distinguish from secondary causes
  • Other tests:
    • Iron studies
    • B12 and folate
    • Liver function
    • Uric acid (often elevated)

Differential Diagnosis

  • Secondary polycythemia:
    • Chronic hypoxia
    • Sleep apnea
    • Smoking
    • High altitude
    • EPO-producing tumors
  • Apparent polycythemia:
    • Dehydration
    • Diuretic use
    • Gaisbock syndrome
  • Other MPNs:
    • Essential thrombocythemia
    • Primary myelofibrosis

Treatment

Treatment Goals

  • Reduce thrombosis risk
  • Control symptoms
  • Minimize disease progression
  • Maintain quality of life

Risk Stratification

  • Low risk:
    • Age <60 years
    • No thrombosis history
  • High risk:
    • Age ≥60 years OR
    • Prior thrombosis

Phlebotomy

  • First-line for all patients
  • Target hematocrit:
    • Men: <45%
    • Women: <42%
  • Procedure:
    • Remove 300-500 mL blood
    • Weekly initially
    • Then as needed
  • Monitor for iron deficiency

Aspirin Therapy

  • Low-dose (81-100 mg daily)
  • All patients unless contraindicated
  • Reduces thrombosis risk
  • Treats erythromelalgia
  • Caution with extreme thrombocytosis

Cytoreductive Therapy

Indications:

  • High-risk patients
  • Poor phlebotomy tolerance
  • Symptomatic splenomegaly
  • Progressive leukocytosis/thrombocytosis
  • Severe symptoms

First-Line Options:

  • Hydroxyurea:
    • Most commonly used
    • Starting dose: 15-20 mg/kg/day
    • Monitor blood counts
    • Side effects: leg ulcers, skin changes
  • Interferon-alpha:
    • Pegylated forms available
    • No leukemogenic risk
    • Safe in pregnancy
    • Side effects: flu-like symptoms, depression

Second-Line Options:

  • Ruxolitinib:
    • JAK1/2 inhibitor
    • For hydroxyurea resistance/intolerance
    • Excellent symptom control
    • Reduces spleen size
  • Busulfan:
    • Older patients
    • Limited life expectancy
    • Leukemogenic risk

Supportive Care

  • Allopurinol: For hyperuricemia
  • H2 blockers: For GI symptoms
  • Antihistamines: For pruritus
  • PUVA therapy: Severe pruritus

Living with Polycythemia Vera

Lifestyle Modifications

  • Hydration:
    • Drink plenty of water
    • Especially important
    • Reduces blood viscosity
  • Exercise:
    • Regular moderate activity
    • Improves circulation
    • Avoid extreme exertion
  • Temperature extremes:
    • Avoid very hot baths (pruritus)
    • Protect from cold (circulation)
  • Smoking cessation:
    • Critical importance
    • Increases thrombosis risk
    • Worsens symptoms

Monitoring

  • Regular blood counts:
    • Monthly initially
    • Every 3-6 months when stable
  • Annual assessments:
    • Spleen size
    • Cardiovascular evaluation
    • Bone marrow (if indicated)
  • Watch for progression:
    • Increasing spleen size
    • Falling blood counts
    • Constitutional symptoms

Managing Specific Symptoms

  • Pruritus:
    • Cool water for bathing
    • Pat dry, don't rub
    • Moisturizers
    • Antihistamines
    • Phototherapy
  • Headaches:
    • Maintain hematocrit goals
    • Adequate hydration
    • Stress management
  • Fatigue:
    • Regular sleep schedule
    • Balanced activity
    • Address anemia if present

Thrombosis Prevention

  • Maintain target hematocrit
  • Take aspirin as prescribed
  • Stay active
  • Avoid prolonged immobility
  • Compression stockings for travel
  • Recognize warning signs

Complications

Thrombotic Complications

  • Major cause of morbidity/mortality
  • Risk factors:
    • Age >60
    • Prior thrombosis
    • Leukocytosis
    • JAK2 allele burden >50%

Disease Transformation

  • Post-PV myelofibrosis:
    • 10-20% at 15 years
    • Cytopenias develop
    • Increasing splenomegaly
    • Constitutional symptoms
  • Acute myeloid leukemia:
    • 2-5% risk
    • Higher with certain treatments
    • Poor prognosis

Other Complications

  • Bleeding (with extreme thrombocytosis)
  • Gout
  • Kidney stones
  • Peptic ulcer disease
  • Hypertension

Prognosis

Life Expectancy

  • Median survival: 14-20 years from diagnosis
  • With treatment, many live normal lifespans
  • Younger patients have better prognosis
  • Major causes of death:
    • Thrombosis
    • Disease transformation
    • Other malignancies

Prognostic Factors

  • Favorable:
    • Younger age
    • No thrombosis history
    • Good treatment response
    • Lower JAK2 burden
  • Unfavorable:
    • Age >60
    • Prior thrombosis
    • Leukocytosis >15,000
    • Abnormal karyotype

With modern management including phlebotomy, aspirin, and cytoreductive therapy when needed, most patients with PV can expect good disease control and quality of life. Regular monitoring and adherence to treatment are key to preventing complications and achieving the best possible outcomes.