Management of Elevated RBC Count, Hematocrit, and Hemoglobin
First, ensure adequate hydration to distinguish true erythrocytosis from relative erythrocytosis caused by dehydration or hemoconcentration, then proceed with targeted diagnostic workup to identify the underlying cause. 1, 2
Initial Assessment and Hydration
Ensure adequate hydration as first-line therapy for all patients with erythrocytosis, as this is the most critical initial step to determine if the elevation represents true versus relative polycythemia. 1
Assess for symptoms of hyperviscosity including headache, visual disturbances, fatigue, or poor concentration, which indicate the need for more urgent intervention. 1
Evaluate for cardiopulmonary symptoms suggesting hypoxemia as a potential secondary cause of erythrocytosis. 1
Diagnostic Workup
Order a non-fasting CBC with differential to confirm persistent elevation and rule out hemoconcentration from fasting. 2
Laboratory Testing Priority:
JAK2 V617F mutation testing is essential, as it is present in >95% of polycythemia vera cases and distinguishes primary from secondary causes. 2, 3
Serum erythropoietin (EPO) level should be measured; it is typically low or low-normal in polycythemia vera, while elevated levels suggest secondary erythrocytosis. 4, 2, 3
Assess iron status with serum ferritin and transferrin saturation, as iron deficiency can mask the full extent of erythrocytosis while increasing stroke risk. 1
Perform peripheral blood smear to evaluate red cell morphology and red cell distribution width (RDW). 1
Important Diagnostic Consideration:
Note that while low EPO is a minor WHO criterion for polycythemia vera diagnosis, some PV patients can present with elevated EPO levels, so a high EPO does not exclude PV if other criteria are met. 5 This is why JAK2 mutation testing is critical regardless of EPO level.
Risk Stratification
Two risk categories determine treatment intensity: 3, 6
- High-risk: Age >60 years OR history of thrombosis
- Low-risk: Absence of both risk factors
Additional thrombosis risk factors include cardiovascular risk factors (for arterial thrombosis), higher absolute neutrophil count, and JAK2V617F allele burden (for venous thrombosis). 3
Management Approach
All Patients (Regardless of Risk):
Maintain hematocrit target <45% through periodic phlebotomy, as this is the backbone of treatment for all patients with confirmed polycythemia vera. 3, 6, 7
Initiate once- or twice-daily aspirin (81 mg) therapy unless contraindicated, to prevent thrombotic complications. 2, 3, 6
Continue aspirin therapy even during diagnostic workup if myeloproliferative disorder is suspected. 2
High-Risk Patients:
Add cytoreductive therapy with first-line drugs: 3, 6
- Hydroxyurea is the first-line cytoreductive agent of choice
- Pegylated interferon-α is an alternative first-line option
- Busulfan and ruxolitinib are reserved for second-line therapy
Secondary Erythrocytosis Management:
Treat the underlying cause such as hypoxemia, sleep apnea, or other secondary conditions. 1
Avoid routine phlebotomy unless hemoglobin >20 g/dL and hematocrit >65%, or symptoms of hyperviscosity are present. 1
Monitor hemoglobin and hematocrit periodically in patients with secondary erythrocytosis. 1
Critical Pitfalls to Avoid
Do not perform routine phlebotomies without confirming the diagnosis, as this can lead to iron depletion, decreased oxygen-carrying capacity, and paradoxically increased stroke risk. 1
Iron deficiency in erythrocytosis increases stroke risk and should be corrected with cautious supplementation and close monitoring of hemoglobin levels. 1 However, recognize that iron deficiency can mask the full extent of erythrocytosis while still contributing to hyperviscosity symptoms. 1
Do not delay hematology referral if non-fasting CBC remains elevated after initial assessment, as definitive diagnosis and management require specialist input. 2
Special Considerations
For patients with venous thrombosis history, systemic anticoagulation is advised in addition to standard therapy. 3
Bone marrow biopsy with cytogenetic analysis is recommended if diagnosis remains unclear after initial testing, as abnormal karyotype is seen in 15-20% of PV patients and has prognostic implications. 3
Screen for acquired von Willebrand syndrome before administering aspirin in patients with extreme thrombocytosis, as this increases bleeding risk. 8