What is Polycythemia Vera (PV), a myeloproliferative neoplasm?

From the Guidelines

Polycythemia vera is a chronic myeloproliferative neoplasm that requires immediate management with phlebotomy to maintain hematocrit below 45% and low-dose aspirin to reduce thrombotic risk, as evidenced by the European LeukemiaNet recommendations 1 and the ESMO clinical practice guidelines 1.

Key Characteristics of Polycythemia Vera

• Characterized by excessive production of red blood cells, leading to increased blood viscosity and thrombotic risk
• Results from acquired mutations, primarily JAK2 V617F in 95% of cases, leading to constitutive activation of the JAK-STAT pathway
• Requires risk stratification to guide treatment, with low-risk patients managed with phlebotomy and aspirin, and high-risk patients requiring cytoreductive therapy

Treatment Approach

• Low-risk patients (age <60 and no history of thrombosis) should be managed with low-dose aspirin (81-100mg daily) and phlebotomy to maintain hematocrit below 45% 1
• High-risk patients require cytoreductive therapy, with hydroxyurea as first-line treatment (starting at 500-1000mg daily, adjusted based on blood counts) 1
• Interferon-alpha (particularly pegylated forms) is preferred for younger patients or those planning pregnancy 1
• Ruxolitinib, a JAK inhibitor, is beneficial for patients with significant splenomegaly or symptoms unresponsive to hydroxyurea

Lifestyle Modifications and Monitoring

• Patients should be monitored regularly for disease progression, thrombotic events, and transformation to myelofibrosis or acute leukemia
• Lifestyle modifications include adequate hydration, avoiding extreme temperatures, and managing cardiovascular risk factors
• Aquagenic pruritus can be treated with IFN-α, JAK2 inhibitors, antihistamines, selective serotonin reuptake inhibitors, or PUVA therapy 1

From the Research

Definition and Characteristics of Polycythemia Vera (PV)

• Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis 2.
• PV is associated with erythrocytosis, thrombocytosis, and leukocytosis, as well as symptoms such as pruritus, erythromelalgia, and splenomegaly 2, 3.
• The presence of a JAK2 gene variant is a key diagnostic criterion for PV, with more than 95% of patients having this mutation 2.

Diagnosis and Risk Stratification

• Diagnosis of PV is based on bone marrow morphology and the presence of a JAK2 mutation 4.
• Risk stratification in PV is designed to estimate the likelihood of thrombotic complications, with high-risk patients defined as those aged 60 years or older or with a prior thrombosis 2, 3.
• Other risk factors for thrombosis in PV include cardiovascular risk factors and the presence of extreme thrombocytosis 3, 5.

Treatment and Management

• The main goal of therapy in PV is to prevent thrombohemorrhagic complications, with treatment options including phlebotomy, low-dose aspirin, and cytoreductive therapy with hydroxyurea or interferon 2, 3, 4.
• Patients with high-risk PV may benefit from cytoreductive therapy to lower thrombosis risk and decrease symptoms 2, 3.
• Ruxolitinib, a Janus kinase inhibitor, may be used to alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea 2, 6.

Prognosis and Complications

• The median survival from diagnosis of PV is 14.1 to 27.6 years, with a 10-year risk of leukemic or fibrotic transformation of <3% and <10%, respectively 2, 4.
• PV is associated with an increased risk of arterial and venous thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia 2, 3.
• Patients with PV may also develop acquired von Willebrand disease, which can increase the risk of bleeding 3, 5.