From the Guidelines
The workup of polycythemia should begin with a complete blood count to confirm elevated hemoglobin and hematocrit, followed by serum erythropoietin level, JAK2 mutation testing, and bone marrow biopsy to distinguish between primary and secondary causes. The initial evaluation is crucial in determining the underlying cause of polycythemia, which can be either primary (polycythemia vera) or secondary. Essential tests include:
- Serum erythropoietin level to determine if it's low, normal, or high, which can help in differentiating between primary and secondary polycythemia 1
- JAK2 mutation testing, particularly V617F and exon 12 mutations, to confirm the diagnosis of polycythemia vera 1
- Bone marrow biopsy to assess for characteristic changes such as hypercellularity, increased megakaryocytes, and pleomorphism in megakaryocyte morphology 1
If erythropoietin is low or normal with positive JAK2 mutation, polycythemia vera is likely. For elevated erythropoietin, investigate secondary causes including:
- Hypoxemia (arterial blood gas, sleep study for sleep apnea)
- Renal disease (ultrasound, creatinine)
- Tumors that secrete erythropoietin (abdominal CT scan for renal cell carcinoma, hepatocellular carcinoma, or cerebellar hemangioblastoma) 1
Additional testing should include iron studies, as iron deficiency can mask the degree of polycythemia, and screening for thrombotic risk factors. Patients with confirmed polycythemia vera require cytoreductive therapy, phlebotomy to maintain hematocrit <45%, and low-dose aspirin to reduce thrombotic complications, as recommended by the European LeukemiaNet 1.
The most recent and highest quality study, the CYTO-PV trial, demonstrated that intensive phlebotomy treatment (target hematocrit < 45%) significantly reduces the risk of cardiovascular events and major thrombotic events compared to less intensive phlebotomy treatment (target hematocrit 45-50%) 1. Therefore, intensive phlebotomy treatment should be the goal in managing patients with polycythemia vera.
From the Research
Diagnostic Criteria for Polycythemia Vera
- Erythrocytosis (hemoglobin >16.5 mg/dL in men or >16.0 mg/dL in women) is a required diagnostic criterion 2
- Presence of a JAK2 gene variant helps distinguish PV from secondary causes of erythrocytosis, such as tobacco smoking or sleep apnea 2, 3, 4
- Bone marrow morphology remains the cornerstone of diagnosis, and morphologic confirmation by bone marrow examination is advised but not mandated 4, 5
- Subnormal erythropoietin level is a minor criterion that helps differentiate polycythemia vera from common causes of secondary erythrocytosis 6
Clinical Features of Polycythemia Vera
- Patients may have pruritus, erythromelalgia, transient visual changes, and splenomegaly with abdominal discomfort 2
- Thrombocytosis (53%) and leukocytosis (49%) are common 2
- Increased risk of arterial and venous thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia 2, 3, 4, 5
Risk Stratification and Management
- Two risk categories are considered: high (age >60 years or thrombosis history) and low (absence of both risk factors) 2, 3, 4, 5
- All patients with PV should receive therapeutic phlebotomy (goal hematocrit, <45%) and low-dose aspirin (if no contraindications) 2, 3, 4, 5, 6
- Cytoreductive therapy with hydroxyurea or interferon is recommended for patients at high risk of thrombosis or with persistent PV symptoms 2, 3, 4, 5, 6
- Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea 2, 5