Polycythemia Vera: Symptoms, Causes, Treatment

What are the symptoms of polycythemia vera?

Polycythemia vera (PV) is a rare blood disorder characterized by an increased production of red blood cells, and sometimes white blood cells and platelets, leading to thicker blood and an increased risk of clotting. The symptoms of polycythemia vera can vary widely and may develop slowly over time. Common symptoms include:

1. General Symptoms

• Fatigue: Persistent tiredness or weakness.
• Headache: Frequent or severe headaches.
• Dizziness or Lightheadedness: Feeling dizzy or faint.

2. Cardiovascular Symptoms

• High Blood Pressure: Elevated blood pressure levels.
• Chest Pain: Discomfort or pain in the chest.

3. Vascular and Blood-related Symptoms

• Redness of the Skin: Especially noticeable on the face, hands, and feet.
• Itching: Often worsened by warm baths or showers (aquagenic pruritus).
• Swelling: In the hands and feet, sometimes accompanied by a burning sensation.
• Blood Clots: Increased risk of clotting, which can lead to complications like deep vein thrombosis, pulmonary embolism, or stroke.

4. Abdominal Symptoms

• Splenomegaly: Enlargement of the spleen, which can cause abdominal pain or discomfort and a feeling of fullness.
• Early Satiety: Feeling full after eating small amounts of food, due to an enlarged spleen pressing against the stomach.

5. Neurological Symptoms

• Blurred Vision: Visual disturbances, including blurred or double vision.
• Tingling or Numbness: Sensations in the hands or feet.

6. Other Symptoms

• Excessive Sweating: Particularly at night (night sweats).
• Unintended Weight Loss: Loss of appetite and weight without trying.

It’s important to note that some people with polycythemia vera may not experience noticeable symptoms, especially in the early stages of the disease. If left untreated, PV can lead to more serious complications, including an increased risk of blood clots, which can result in heart attack, stroke, or other life-threatening conditions. If you experience symptoms suggestive of PV, it’s important to seek medical evaluation for an accurate diagnosis and appropriate management.

What are the causes of polycythemia vera?

Polycythemia vera (PV) is a type of blood cancer, specifically a myeloproliferative neoplasm, characterized by the overproduction of red blood cells, and sometimes white blood cells and platelets, in the bone marrow. The exact cause of polycythemia vera is not fully understood, but it is primarily associated with a genetic mutation.

Causes and Risk Factors

1. Genetic Mutation:

• JAK2 Mutation: The majority of PV cases are associated with a mutation in the JAK2 (Janus kinase 2) gene. This mutation leads to abnormal signaling that causes the bone marrow to produce too many blood cells. The JAK2 V617F mutation is found in about 95% of people with PV. A small percentage of PV patients may have mutations in other genes related to blood cell production.

1. Clonal Hematopoiesis:

• In PV, there is an abnormal expansion of a clone of hematopoietic (blood-forming) stem cells in the bone marrow, driven by the JAK2 mutation. This clonal expansion results in the excessive production of blood cells.

1. Risk Factors:

• Age: PV is more common in older adults, typically developing in people over 60 years old.
• Family History: While most cases of PV are not inherited, having a family history of myeloproliferative disorders may slightly increase the risk.

Polycythemia vera is generally not considered hereditary, meaning it is not typically passed down from parents to children. The JAK2 mutation associated with PV usually arises spontaneously. Because it involves the overproduction of blood cells and is driven by a genetic mutation, PV requires medical management and monitoring to prevent complications related to increased blood viscosity and clotting risks.

How is the diagnosis of polycythemia vera made?

The diagnosis of polycythemia vera (PV) is typically made through a combination of clinical evaluation, laboratory tests, and sometimes imaging studies. The diagnostic process aims to confirm the presence of an elevated red blood cell mass and identify the underlying cause. The following are key steps and criteria used in diagnosing PV:

1. Clinical Evaluation

• Medical History and Physical Examination: The doctor will review the patient’s medical history, symptoms, and perform a physical examination, focusing on signs such as an enlarged spleen (splenomegaly), skin redness, and other symptoms associated with PV.

2. Laboratory Tests

• Complete Blood Count (CBC):
  • Elevated Hemoglobin and Hematocrit Levels: Indicating an increased red blood cell mass.
  • Leukocytosis: An elevated white blood cell count.
  • Thrombocytosis: An elevated platelet count.
• Blood Smear: Examining a blood sample under a microscope to assess the appearance and number of blood cells.
• Erythropoietin (EPO) Levels: PV is often associated with low or normal levels of erythropoietin, a hormone that stimulates red blood cell production. Elevated EPO levels usually suggest other conditions.

3. Genetic Testing

• JAK2 Mutation Test: Testing for the presence of the JAK2 V617F mutation or other JAK2 exon 12 mutations. The presence of these mutations strongly supports a diagnosis of PV, as they are found in most patients with the disease.

4. Bone Marrow Examination

• Bone Marrow Biopsy and Aspiration: This procedure involves taking a sample of bone marrow tissue to examine under a microscope. In PV, the bone marrow typically shows hypercellularity (an increased number of blood-forming cells) and other characteristic changes.

5. Additional Diagnostic Criteria

• Serum Erythropoietin Level: As mentioned, low or normal levels are typical in PV.
• Red Cell Mass Measurement: In some cases, a red cell mass study may be performed to measure the total volume of red blood cells in the body.

6. Exclusion of Secondary Causes

• It is important to rule out other conditions that can cause increased red blood cell production, such as chronic hypoxia (due to lung disease or living at high altitudes), tumors that produce erythropoietin, or other myeloproliferative disorders.

Diagnostic Criteria

The World Health Organization (WHO) has established criteria for diagnosing PV, which include a combination of major and minor criteria based on laboratory findings and genetic testing. A diagnosis is typically made when:

• Two major criteria and one minor criterion are met, or
• The presence of all three major criteria.

Major Criteria

1. Elevated hemoglobin, hematocrit, or red cell mass.
2. Presence of the JAK2 V617F or JAK2 exon 12 mutation.
3. Hypercellular bone marrow with increased erythroid, granulocytic, and megakaryocytic proliferation.

Minor Criteria

1. Subnormal serum erythropoietin level.

Accurate diagnosis of PV is crucial for appropriate management and treatment. If you suspect you have symptoms related to PV, consult with a healthcare provider or a hematologist for a thorough evaluation.

What is the treatment for polycythemia vera?

The treatment of polycythemia vera (PV) aims to reduce the risk of complications, such as blood clots, and manage symptoms. Since PV is a chronic condition with no known cure, treatment focuses on controlling blood counts and reducing symptoms. The treatment plan may vary based on factors such as age, overall health, the presence of symptoms, and the risk of thrombotic events. Common treatments include:

1. Phlebotomy

• Procedure: The removal of blood from the body, similar to donating blood.
• Purpose: To decrease the number of red blood cells, thereby reducing blood viscosity and the risk of clotting.
• Frequency: The frequency of phlebotomy sessions depends on the individual’s hematocrit level and response to treatment.

2. Medications

• Cytoreductive Therapy: Medications that reduce the production of blood cells in the bone marrow.
  • Hydroxyurea: A commonly used medication that suppresses bone marrow activity. It is often used in high-risk patients, such as those with a history of thrombosis or older individuals.
  • Interferon-alpha: An alternative to hydroxyurea, often used in younger patients or those who cannot tolerate other treatments.
  • Busulfan: Occasionally used as an alternative cytoreductive agent.
• Aspirin: Low-dose aspirin is often prescribed to reduce the risk of blood clots, as it has an antiplatelet effect.
• Ruxolitinib (Jakafi): A JAK1 and JAK2 inhibitor that can help reduce symptoms and control blood counts, especially in patients who are resistant or intolerant to hydroxyurea.

3. Management of Symptoms and Complications

• Antihistamines: For relief from itching (pruritus), which is a common symptom of PV.
• Treatment of Gout: Medications such as allopurinol may be used to manage elevated uric acid levels, which can lead to gout.
• Management of Splenomegaly: In cases of an enlarged spleen, treatment may involve medication, radiation, or, in rare cases, surgical removal.

4. Lifestyle and Supportive Care

• Regular Monitoring: Ongoing monitoring of blood counts and symptoms is crucial to adjust the treatment plan as needed.
• Lifestyle Changes: Maintaining a healthy lifestyle, including regular exercise, a balanced diet, and quitting smoking, can help reduce the risk of complications.
• Hydration: Staying well-hydrated can help reduce blood viscosity.

5. Clinical Trials and New Therapies

• Participation in clinical trials may be an option for patients seeking access to new and experimental therapies.

6. Special Considerations

• Pregnancy: Women with PV who are pregnant require special management and monitoring to ensure the safety of both the mother and the baby.

Regular follow-up with a hematologist is essential for patients with PV to monitor the disease and adjust the treatment plan as needed. Treatment aims to manage the disease, alleviate symptoms, and minimize the risk of complications.