Overview

Polycythemia vera (PV) is a rare, chronic blood disorder characterized by the overproduction of red blood cells in the bone marrow. It is classified as a myeloproliferative neoplasm (MPN), which means it originates from the uncontrolled growth of blood-forming cells. The excess red blood cells cause the blood to thicken, increasing the risk of blood clots, strokes, and other serious complications. In addition to red cells, white blood cells and platelets may also be elevated. Polycythemia vera is a slowly progressive disease, and although it cannot be cured, effective treatments can manage symptoms and reduce risks associated with the condition.

Causes

The exact cause of polycythemia vera is not fully understood, but it is almost always linked to a genetic mutation in blood-forming stem cells. The primary cause is:

• JAK2 Mutation: About 95% of people with PV have a mutation in the Janus kinase 2 (JAK2) gene, specifically JAK2 V617F. This mutation causes cells in the bone marrow to produce excessive blood cells independently of normal regulatory mechanisms.

Polycythemia vera is not inherited but occurs as an acquired mutation during a person’s lifetime. Risk factors include:

• Age: Most cases are diagnosed in people over 60 years old, although it can also affect younger individuals.
• Gender: PV affects both men and women, but it is slightly more common in men.
• No Known Environmental Triggers: Unlike some other cancers, polycythemia vera is not strongly associated with environmental exposures like chemicals or radiation.

Symptoms

Polycythemia vera can cause a wide range of symptoms, varying in severity from person to person. Some individuals may remain asymptomatic for years, while others experience significant discomfort. Common symptoms include:

• Headaches: Caused by increased blood thickness and reduced oxygen delivery.
• Itching (Pruritus): Particularly after warm showers or baths, due to increased histamine release.
• Reddened Skin (Plethora): Especially on the face, hands, and feet, giving a ruddy complexion.
• Enlarged Spleen (Splenomegaly): Causing a sensation of fullness or discomfort in the left upper abdomen.
• Fatigue and Weakness: Persistent tiredness despite adequate rest.
• Blurred Vision or Dizziness: Due to increased blood viscosity.
• Night Sweats and Weight Loss: Less common but possible, indicating systemic effects of the disease.
• Thrombosis (Blood Clots): Increased risk of deep vein thrombosis (DVT), pulmonary embolism, stroke, or heart attack.
• Gout and Joint Pain: Caused by increased uric acid levels from rapid cell turnover.

Diagnosis

Diagnosing polycythemia vera involves a combination of clinical evaluation, laboratory testing, and genetic analysis. Diagnostic steps include:

• Complete Blood Count (CBC): Shows elevated red blood cells, hemoglobin, and hematocrit levels; white cells and platelets may also be increased.
• JAK2 Mutation Testing: A positive result for the JAK2 V617F mutation confirms the clonal nature of the disorder.
• Erythropoietin (EPO) Levels: Typically low in PV, helping to differentiate from secondary causes of polycythemia.
• Bone Marrow Biopsy: May be performed to examine marrow cellularity and rule out other hematological disorders.
• Oxygen Saturation and Imaging: Used to exclude secondary causes like chronic lung disease or tumors that can elevate red cell count.
• Red Cell Mass Measurement: In specialized cases, a nuclear medicine test may be used to confirm true polycythemia.

Treatment

Although there is no cure for polycythemia vera, treatment focuses on reducing blood thickness, preventing clotting events, and managing symptoms. Common treatment strategies include:

• Phlebotomy: The removal of blood at regular intervals is the first-line treatment to reduce hematocrit levels below 45% in men and below 42% in women.
• Low-Dose Aspirin: Helps prevent blood clots by reducing platelet aggregation and improving blood flow.
• Cytoreductive Therapy: Medications such as hydroxyurea or interferon-alpha are used to suppress bone marrow activity, particularly in high-risk patients.
• JAK Inhibitors: Ruxolitinib, a JAK1/2 inhibitor, may be prescribed in resistant or intolerant cases to reduce symptoms and spleen size.
• Antihistamines: Used to relieve itching, especially after bathing.
• Lifestyle Adjustments: Maintaining hydration, avoiding extreme temperatures, quitting smoking, and regular exercise can help manage symptoms and reduce risk factors.

Prognosis

With proper management, individuals with polycythemia vera can live for many years. Key points regarding prognosis include:

• Life Expectancy: Many patients live 15-20 years after diagnosis with appropriate treatment and monitoring.
• Risk of Complications: The main risks are thrombotic events (blood clots), which can cause serious complications like strokes or heart attacks if not well controlled.
• Progression Risk: A small percentage of cases may progress to myelofibrosis (marrow scarring) or transform into acute myeloid leukemia (AML), especially in those requiring aggressive cytoreductive therapy.
• Regular Monitoring: Lifelong follow-up with a hematologist is crucial to manage the disease, adjust treatments, and prevent complications.

Early diagnosis and consistent management have dramatically improved outcomes, allowing most patients with polycythemia vera to maintain a good quality of life and minimize serious health risks.