Polycythemia Vera (PV) is a clonal hematopoietic stem cell disorder classified under myeloproliferative neoplasms (MPNs). It is characterized by the overproduction of red blood cells (erythrocytosis), leading to increased blood viscosity and a heightened risk of thrombosis. Although the primary feature is erythrocytosis, PV can also involve elevated white blood cells (leukocytosis) and platelets (thrombocytosis). The pathogenesis of PV is strongly associated with the JAK2 V617F mutation, present in approximately 95% of cases, which leads to constitutive activation of the JAK-STAT signaling pathway, promoting uncontrolled cell proliferation. PV has an insidious onset and is often diagnosed during routine blood tests. Untreated, PV can progress to myelofibrosis or transform into acute myeloid leukemia (AML), although this is relatively rare.

The diagnosis of Polycythemia Vera is based on a combination of clinical, laboratory, and molecular criteria, as outlined by the World Health Organization (WHO). Key diagnostic criteria include elevated hemoglobin (>16.5 g/dL in men, >16.0 g/dL in women) or hematocrit (>49% in men, >48% in women), along with bone marrow biopsy findings showing hypercellularity with prominent erythroid, granulocytic, and megakaryocytic proliferation. The presence of the JAK2 V617F mutation is a major diagnostic criterion, as it is found in nearly all PV patients. Serum erythropoietin (EPO) levels are typically low in PV, helping to distinguish it from secondary causes of erythrocytosis. Additional tests may include bone marrow biopsy and aspiration to assess cellular morphology and exclude other myeloproliferative disorders, and erythropoietin levels to differentiate from secondary erythrocytosis. If necessary, endogenous erythroid colony formation can be assessed to confirm autonomous erythropoiesis.

Prognostic evaluation in PV primarily focuses on the risk of thrombotic events, disease progression, and transformation to myelofibrosis or AML. Key risk factors for thrombosis include age >60 years, a history of thrombosis, and cardiovascular risk factors such as smoking and hypertension. Leukocytosis and the presence of JAK2 V617F allele burden have also been associated with an increased risk of thrombosis. Prognostic models, such as the International Prognostic Score for Thrombosis in PV (IPSET-Thrombosis), are used to stratify patients based on their thrombotic risk, guiding therapeutic decisions. Progression to myelofibrosis, known as post-PV myelofibrosis, is a significant concern, and factors such as high red cell mass, leukocytosis, and bone marrow fibrosis at diagnosis have been linked to an increased risk of progression. In rare cases, PV can transform into acute myeloid leukemia (AML), with an estimated transformation rate of 2-5% over 20 years.

Prognostic evaluation in PV primarily focuses on the risk of thrombotic events, disease progression, and transformation to myelofibrosis or AML. Key risk factors for thrombosis include age >60 years, a history of thrombosis, and cardiovascular risk factors such as smoking and hypertension. Leukocytosis and the presence of JAK2 V617F allele burden have also been associated with an increased risk of thrombosis. Prognostic models, such as the International Prognostic Score for Thrombosis in PV (IPSET-Thrombosis), are used to stratify patients based on their thrombotic risk, guiding therapeutic decisions. Progression to myelofibrosis, known as post-PV myelofibrosis, is a significant concern, and factors such as high red cell mass, leukocytosis, and bone marrow fibrosis at diagnosis have been linked to an increased risk of progression. In rare cases, PV can transform into acute myeloid leukemia (AML), with an estimated transformation rate of 2-5% over 20 years.

The primary goals of treating Polycythemia Vera are to reduce thrombotic risk, manage symptoms, and prevent disease progression. Phlebotomy is the cornerstone of treatment, aiming to maintain hematocrit levels below 45%, which has been shown to reduce the risk of thrombotic events. Low-dose aspirin (81-100 mg daily) is recommended for all patients unless contraindicated, as it further reduces thrombotic risk. For high-risk patients, particularly those over 60 or with a history of thrombosis, cytoreductive therapy is indicated to control hematopoiesis. Hydroxyurea is the first-line cytoreductive agent, with interferon-alpha (including its pegylated form) as an alternative, particularly in younger patients or those intolerant to hydroxyurea. Newer therapies, such as ruxolitinib, a JAK1/2 inhibitor, are considered for patients resistant or intolerant to conventional treatments. Ruxolitinib has also shown efficacy in reducing spleen size and symptom burden in PV. For refractory or intolerant patients, busulfan or radioactive phosphorus (32P) may be considered, though these are less commonly used due to long-term risks. Regular monitoring and adjustment of therapy based on hematologic response and symptom control are essential for optimal management.