From the Guidelines
The workup of increased hematocrit should begin with confirmation of the elevated value through repeat testing, followed by a thorough history and physical examination to identify potential causes, with a target hematocrit level of less than 45% to reduce the risk of thrombotic events, as supported by the CYTO-PV study 1. The initial evaluation should include:
- Complete blood count with differential
- Comprehensive metabolic panel
- Erythropoietin level
- Arterial blood gas analysis to assess for hypoxemia If polycythemia vera is suspected, testing for JAK2 V617F mutation should be performed 1. Secondary causes to investigate include:
- Smoking
- Chronic lung disease
- Sleep apnea
- High-altitude living
- Kidney disease Dehydration should be ruled out as a cause of relative polycythemia. For confirmed absolute polycythemia, bone marrow biopsy may be necessary to differentiate between primary and secondary causes. Management depends on the underlying cause but may include:
- Therapeutic phlebotomy to maintain hematocrit below 45% in men and 42% in women, as recommended by the NCCN guidelines 1
- Hydration
- Smoking cessation
- Treatment of underlying conditions Patients with polycythemia vera may require cytoreductive therapy such as hydroxyurea starting at 500-1000 mg daily and adjusted based on blood counts, as recommended by the ESMO clinical practice guidelines 1. Aspirin 81 mg daily is often recommended to reduce thrombotic risk, as shown in the European Collaboration on Low-dose Aspirin in Polycythaemia Vera (ECLAP) study 1. Regular monitoring of blood counts is essential, with frequency determined by the severity of the condition and treatment approach. Addressing increased hematocrit promptly is important as it raises blood viscosity and increases risk of thrombotic events including stroke and myocardial infarction.
From the Research
Work-up of Increased Hematocrit
- The work-up of increased hematocrit involves evaluating the patient for polycythemia vera (PV), a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis 2, 3.
- The diagnosis of PV is based on the presence of a JAK2 gene variant, which is found in more than 95% of patients with PV 2.
- Other features of PV include leukocytosis, thrombocytosis, splenomegaly, pruritus, and constitutional symptoms 2, 3.
- The work-up of increased hematocrit should also include an evaluation for secondary causes of erythrocytosis, such as tobacco smoking or sleep apnea 2.
Diagnostic Criteria
- The diagnostic criteria for PV include a hemoglobin level of >16.5 mg/dL in men or >16.0 mg/dL in women, and the presence of a JAK2 gene variant 2, 3.
- A bone marrow examination may be performed to confirm the diagnosis, but it is not mandatory 3.
- The World Health Organization (WHO) diagnostic guidelines for PV are not helpful in cases where the hematocrit is normal, and a direct measurement of both the red cell mass and plasma volume may be necessary to establish the correct diagnosis 4.
Risk Stratification
- Patients with PV should be stratified according to their risk of thrombosis, with high-risk patients being those aged 60 years or older or with a prior thrombosis 2, 3.
- The risk of thrombosis in PV patients can be reduced with therapeutic phlebotomy and low-dose aspirin 2, 3.
- Cytoreductive therapy with hydroxyurea or interferon may be necessary for high-risk patients or those with persistent symptoms 2, 3.
Management
- The management of PV involves therapeutic phlebotomy to maintain a hematocrit of less than 45%, and low-dose aspirin to reduce the risk of thrombosis 2, 3.
- Cytoreductive therapy with hydroxyurea or interferon may be necessary for high-risk patients or those with persistent symptoms 2, 3.
- Patients with PV should be followed up regularly to monitor their blood cell counts and splenomegaly, and to adjust their treatment as necessary 5.