Management of Persistent Erythrocytosis with New-Onset Leukocytosis
This patient requires immediate evaluation for polycythemia vera (PV), as the combination of persistent erythrocytosis for over a year with new leukocytosis is a classic presentation of this myeloproliferative neoplasm. 1, 2
Immediate Diagnostic Workup
Obtain JAK2 V617F mutation testing immediately, as almost all PV patients harbor this mutation and its presence highly suggests the diagnosis. 2, 3 The classical presentation of PV includes erythrocytosis, leukocytosis, and thrombocytosis, often with splenomegaly. 1
Critical Laboratory Assessment
Perform a complete blood count with differential to assess all three cell lines (red cells, white cells, platelets) and examine for left shift or immature cells. 4, 5
Obtain peripheral blood smear to evaluate cell morphology, maturity, and rule out acute leukemia or other primary bone marrow disorders. 4, 5
Check serum erythropoietin level: In PV, this is typically low or normal, and if elevated with absent JAK2 mutation, PV is excluded. 3
Bone marrow aspiration and biopsy should be performed, as bone marrow morphology remains the cornerstone of PV diagnosis. 2
Physical Examination Priorities
Assess for splenomegaly, which is common in PV and helps distinguish it from secondary erythrocytosis. 1, 2
Evaluate for signs of thrombosis (neurological deficits, chest pain, leg swelling), as PV has the highest incidence of thromboembolic complications among myeloproliferative neoplasms. 1
Screen for bleeding manifestations (bruising, petechiae), weight loss, and constitutional symptoms that might suggest acute leukemia or other malignancy. 5, 6
Risk Stratification for Thrombosis
Classify the patient into high-risk or low-risk categories immediately, as this determines treatment intensity. 2, 3
- High-risk PV: Age >60 years OR history of thrombosis
- Low-risk PV: Absence of both risk factors
Additional thrombotic risk factors include JAK2V617F mutation presence and cardiovascular risk factors, which should be documented. 3
Immediate Management While Awaiting Definitive Diagnosis
If White Blood Cell Count >100,000/μL (Hyperleukocytosis)
Initiate aggressive intravenous hydration at 2.5-3 liters/m²/day immediately to prevent tumor lysis syndrome and leukostasis complications. 4, 7
Start hydroxyurea 50-60 mg/kg/day without delay to achieve 50% WBC reduction within 1-2 weeks if hyperleukocytosis is present. 4
Monitor for leukostasis symptoms (neurological changes, respiratory distress, hypoxia) which constitute a medical emergency requiring potential leukapheresis. 7
If Acute Leukemia Cannot Be Excluded
Do not delay diagnostic workup, but if blast cells are present on peripheral smear, proceed immediately with bone marrow biopsy before initiating definitive therapy. 7
Prompt institution of definitive therapy is essential after measures to rapidly reduce WBC count if acute leukemia is confirmed. 8, 4
Definitive Treatment for Confirmed Polycythemia Vera
Universal Therapy for All PV Patients
Initiate phlebotomy immediately to maintain hematocrit <45%, as this is the cornerstone of PV therapy and reduces thrombotic risk. 2, 3
Start aspirin 81 mg once or twice daily in the absence of contraindications (check for acquired von Willebrand syndrome if platelet count >1,000 × 10⁹/L). 2, 3
Cytoreductive Therapy Indications
High-risk patients require cytoreductive therapy with hydroxyurea as first-line drug of choice. 2, 3
Low-risk patients may be managed with phlebotomy and aspirin alone, without mandatory cytoreductive therapy. 2
Hydroxyurea dosing: Titrate to maintain WBC, platelet counts, and hematocrit within target ranges while monitoring for cytopenias. 2
Second-line options if hydroxyurea fails include interferon-α or busulfan. 2, 3
Critical Pitfalls to Avoid
Do not rely solely on hematocrit to diagnose PV, as plasma volume expansion in PV can mask true erythrocytosis—unless hematocrit is >59%, true erythrocytosis cannot be distinguished from pseudoerythrocytosis. 1
Do not assume isolated thrombocytosis with positive JAK2 excludes PV, particularly in young women, as plasma volume expansion may normalize hematocrit despite elevated red cell mass. 1
Do not use ruxolitinib as first-line therapy in PV unless severe protracted pruritus or marked splenomegaly unresponsive to standard drugs is present. 2
Do not delay treatment while awaiting complete molecular typing if acute leukemia is strongly suspected, as prompt therapy is essential. 7
Avoid repeated routine phlebotomies without monitoring iron status, as iron depletion decreases oxygen-carrying capacity and increases stroke risk. 8
Monitoring and Long-Term Management
Monitor complete blood counts regularly to assess response to phlebotomy and cytoreductive therapy. 2
Screen for disease progression: The 10-year risk of leukemic transformation is <3% and fibrotic transformation is approximately 10% in PV. 2, 3
Median survival for PV is 14 years overall and 24 years in younger patients, making this an indolent disorder requiring decades-long management. 1, 2
Assess for thrombotic complications regularly, as the risk exceeds 20% at 10 years and represents the primary cause of morbidity and mortality. 3