From the Guidelines
Polycythemia vera diagnosis is primarily based on a combination of blood tests, bone marrow examination, and genetic testing for the JAK2 mutation, which is present in about 95% of cases, as stated in the NCCN guidelines insights: myeloproliferative neoplasms, version 2.2018 1.
Diagnosis and Symptoms
The diagnosis requires elevated red blood cell mass (hemoglobin >16.5 g/dL in men or >16.0 g/dL in women), bone marrow showing hypercellularity with trilineage growth, and the presence of JAK2 V617F or similar mutations. Common symptoms include:
- Headaches
- Dizziness
- Visual disturbances
- Itching (especially after warm baths)
- Night sweats
- Reddened skin, particularly on the face, hands, and feet Patients may experience fatigue, weakness, and shortness of breath despite having excess red blood cells because blood flow is compromised by increased viscosity. Many patients are asymptomatic and diagnosed through routine blood work showing elevated hemoglobin and hematocrit levels.
Treatment and Management
Treatment typically involves:
- Phlebotomy to reduce blood thickness
- Low-dose aspirin to prevent clotting
- Medications like hydroxyurea, ruxolitinib, or interferon to reduce blood cell production The goal of treatment is to maintain a hematocrit level <45% to reduce the risk of thrombosis and other complications, as recommended by the NCCN guidelines 1. Complications can include blood clots, bleeding problems, and an enlarged spleen. The disease is a chronic myeloproliferative neoplasm caused by genetic mutations in blood stem cells, leading to overproduction of red blood cells and often white blood cells and platelets as well.
Risk Stratification
Patients are stratified into low-risk and high-risk categories based on age and prior history of thrombosis, with high-risk patients requiring more aggressive treatment and monitoring, as outlined in the NCCN guidelines 1.
From the Research
Diagnosis of Polycythemia Vera
- The diagnosis of Polycythemia Vera (PV) is made by interpreting hematocrit values, red cell count, and red cell mass when available, and bone marrow histomorphology to distinguish PV from other JAK2V617F myeloproliferative neoplasms (MPNs) 2.
- Erythrocytosis (hemoglobin >16.5 mg/dL in men or >16.0 mg/dL in women) is a required diagnostic criterion, although thrombocytosis (53%) and leukocytosis (49%) are common 3.
- The presence of a JAK2 gene variant helps distinguish PV from secondary causes of erythrocytosis, such as tobacco smoking or sleep apnea, and is present in approximately 98% of cases 3, 4.
- Bone marrow morphology remains the cornerstone of diagnosis, and the World Health Organization's major diagnostic criteria include an elevated hemoglobin or hematocrit level, abnormal results on bone marrow biopsy, and presence of the Janus kinase 2 genetic mutation 5, 4.
Symptoms of Polycythemia Vera
- Patients with PV may have pruritus (33%), erythromelalgia (5.3%), transient visual changes (14%), and splenomegaly (36%) with abdominal discomfort 3.
- PV is associated with an increased risk of arterial and venous thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia 3, 5.
- The median survival from diagnosis is 14.1 to 27.6 years, and prior to or at the time of PV diagnosis, arterial thrombosis occurred in 16% of patients and 7% had venous thrombotic events 3.
Treatment of Polycythemia Vera
- All patients with PV should receive therapeutic phlebotomy (goal hematocrit, <45%) and low-dose aspirin (if no contraindications) 3, 4.
- Patients who are at higher risk of thrombosis include those aged 60 years or older or with a prior thrombosis, and these patients and those with persistent PV symptoms may benefit from cytoreductive therapy with hydroxyurea or interferon to lower thrombosis risk and decrease symptoms 3, 5.
- Cytoreductive therapy is recommended for high-risk ET and PV, but it is not mandatory for intermediate-risk ET, and first-line drug of choice for cytoreductive therapy is hydroxyurea, and second-line drugs of choice are interferon-α and busulfan 5, 6.