From the Guidelines
A polycythemia workup should begin with a complete blood count (CBC) to confirm elevated hemoglobin and hematocrit, followed by JAK2 V617F mutation analysis and serum erythropoietin levels to distinguish between primary and secondary polycythemia. The initial evaluation should include testing for JAK2 exon 12 mutations if the V617F mutation is negative but clinical suspicion remains high 1.
Key Components of the Workup
- Complete blood count (CBC) to confirm elevated hemoglobin (>16.5 g/dL in men, >16.0 g/dL in women) and hematocrit (>49% in men, >48% in women)
- JAK2 V617F mutation analysis, which is positive in about 95% of polycythemia vera cases
- Serum erythropoietin levels, which are low in polycythemia vera but normal or elevated in secondary polycythemia
- Additional testing, including comprehensive metabolic panel, arterial blood gas analysis to assess oxygen saturation, and abdominal ultrasound to evaluate spleen size
Secondary Polycythemia Evaluation
For suspected secondary polycythemia, consider:
- Sleep studies for sleep apnea
- Pulmonary function tests
- Echocardiogram to evaluate for cardiopulmonary causes
- Bone marrow biopsy may be necessary if the diagnosis remains unclear after initial testing
Management
According to the most recent guidelines, all patients with polycythemia vera should be managed with phlebotomy to maintain the hematocrit at less than 45% and low-dose aspirin, with cytoreduction indicated in high-risk patients 2, 1.
Risk Stratification
Risk stratification is crucial, with high-risk patients defined as those with age greater than 60 years or a history of previous thrombosis, and managed accordingly with cytoreduction using hydroxyurea or interferon alfa-2 3.
Monitoring and Follow-Up
Regular monitoring for new thrombosis or bleeding, management of cardiovascular risk factors, and evaluation for indications of cytoreductive therapy and signs/symptoms of disease progression every 3–6 months or more frequently if clinically indicated are essential 1.
From the Research
Diagnostic Approach
- The diagnostic approach for polycythemia vera (PV) involves checking for causes of secondary erythrocytosis and studying JAK2 mutations if serum erythropoietin level is low-normal 4.
- In patients with erythrocytosis and other signs of myeloproliferation, such as leukocytosis, thrombocytosis, or splenomegaly, the diagnosis of PV is likely, and serum erythropoietin and JAK2 mutations should be tested first 4.
- Bone marrow morphology remains the cornerstone of diagnosis, and the presence of JAK2 mutation is expected in PV, while approximately 90% of patients with essential thrombocythemia (ET) express mutually exclusive JAK2, CALR, or MPL mutations 5.
Risk Stratification
- Patients with PV can be stratified into two risk categories: high-risk (age >60 years or thrombosis history present) and low-risk (absence of both risk factors) 6, 5, 7, 8.
- In ET, four risk categories are considered: very low (age ≤60 years, no thrombosis history, JAK2 wild-type), low (same as very low but JAK2 mutation present), intermediate (age >60 years, no thrombosis history, JAK2 wild-type), and high (thrombosis history present or age >60 years with JAK2 mutation) 5.
- Risk factors for shortened survival in both PV and ET include advanced age, leukocytosis, and history of thrombosis 7, 8.
Treatment
- The main goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications 6, 5, 7, 8.
- All patients with PV require phlebotomy to keep hematocrit below 45% and once-daily or twice-daily aspirin (81 mg), in the absence of contraindications 6, 5, 8.
- Cytoreductive therapy is recommended for high-risk ET and PV, but it is not mandatory for intermediate-risk ET 5.
- First-line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea, and second-line drugs of choice are interferon-α and busulfan 5, 7, 8.