Management of Elevated White and Red Blood Cell Counts in a Patient in Their 50s
A patient in their 50s with both elevated white and red blood cell counts requires immediate evaluation for a myeloproliferative neoplasm, particularly polycythemia vera (PV), which commonly presents with erythrocytosis (100% of cases), leukocytosis (49%), and thrombocytosis (53%). 1
Immediate Diagnostic Workup
Obtain JAK2V617F mutation testing immediately, as this mutation is present in more than 95% of patients with PV and distinguishes primary myeloproliferative neoplasms from secondary causes of erythrocytosis 1, 2. When PV is suspected, the presence of a JAK2 mutation confirms the diagnosis, and its absence combined with normal or increased serum erythropoietin level excludes the diagnosis 3.
Essential Initial Laboratory Tests
- Complete blood count with differential and peripheral blood smear to assess all cell lines, evaluate for left shift, and examine cell morphology 4, 5
- Serum erythropoietin level to differentiate primary from secondary erythrocytosis 3
- JAK2V617F mutation testing as the definitive diagnostic test 1, 2
- Red blood cell mass and plasma volume measurement if the diagnosis remains unclear after initial testing 6
Rule Out Secondary Causes and Infection
- Assess for infection urgently, as a WBC count >14,000 cells/mm³ has a likelihood ratio of 3.7 for bacterial infection even without fever 4
- Obtain blood cultures before initiating antibiotics if infection is suspected 4
- Evaluate for secondary causes of erythrocytosis including tobacco smoking, sleep apnea, chronic lung disease, and renal pathology 1
- Chest radiograph to evaluate for underlying pulmonary disease or thymoma 7
Risk Stratification for Thrombosis
Age over 60 years or history of prior thrombosis defines high-risk disease requiring cytoreductive therapy in addition to standard management 7, 1. This patient in their 50s would be classified as low-risk unless they have a history of thrombosis.
Additional Risk Assessment
- Screen for extreme thrombocytosis (platelet count ≥1,000 × 10⁹/L), which may cause acquired von Willebrand disease and increase bleeding risk 1, 3
- Calculate IPSET thrombotic risk score if essential thrombocythemia is in the differential: age >60 years (1 point), cardiovascular risk factors (1 point), previous thrombosis (2 points), JAK2V617F mutation (2 points) 7
- Evaluate for constitutional symptoms (fever, weight loss, night sweats) and splenomegaly, which affect prognosis 7
Treatment Algorithm
All Patients with Confirmed PV (Regardless of Risk Category)
Initiate therapeutic phlebotomy immediately with a target hematocrit <45%, as this reduces thrombosis risk and improves survival 1, 2. Phlebotomy should be performed every 2-3 days initially until the target is reached, then as needed to maintain the goal 1.
Start low-dose aspirin (81 mg daily) unless contraindicated to reduce arterial and venous thrombosis risk 1, 2. However, screen for acquired von Willebrand disease before administering aspirin if platelet count exceeds 1,000 × 10⁹/L to avoid increasing bleeding risk 3.
High-Risk Patients (Age ≥60 Years OR Prior Thrombosis)
Add cytoreductive therapy with hydroxyurea or interferon-α as first-line agents to lower thrombosis risk and decrease symptoms 1, 2. Hydroxyurea is typically initiated at 15-20 mg/kg/day and titrated to maintain WBC count 4-10 × 10⁹/L and platelet count 100-400 × 10⁹/L 7.
Criteria for Hydroxyurea Resistance/Intolerance
Consider the patient resistant or intolerant to hydroxyurea if any of the following occur after 3 months of at least 2 g/day 7:
- Failure to reduce massive splenomegaly by >50%
- Uncontrolled myeloproliferation (platelet count >400 × 10⁹/L AND WBC count >10 × 10⁹/L)
- Absolute neutrophil count <1.0 × 10⁹/L or platelet count <50 × 10⁹/L at the lowest effective dose
- Development of leg ulcers or other unacceptable non-hematologic toxicities
For hydroxyurea-resistant or intolerant patients, switch to ruxolitinib (a JAK1/JAK2 inhibitor) to alleviate pruritus, decrease splenomegaly, and reduce symptom burden 1, 2.
Monitoring and Follow-Up
Monitor CBC weekly initially until stable target values are achieved, then every 1-3 months long-term 7. Track JAK2V617F variant allele frequency, as reduction is being evaluated as a treatment target and higher levels correlate with worse prognosis 2.
Long-Term Complications to Monitor
- Thrombosis risk exceeds 20% over 10 years, with both arterial events (16% at diagnosis) and venous events including unusual sites like splanchnic veins (7% at diagnosis) 1, 3
- Transformation to myelofibrosis occurs in 12.7% and acute myeloid leukemia in 6.8% of patients 1
- 10-year risk of leukemic/fibrotic transformation is <3%/10% in PV 3
Critical Pitfalls to Avoid
Do not delay JAK2 mutation testing while pursuing extensive workup for secondary causes, as this delays definitive diagnosis and appropriate therapy 1, 2.
Do not use aspirin in patients with extreme thrombocytosis without first screening for acquired von Willebrand disease, as this significantly increases bleeding risk 3.
Do not target hematocrit levels >45%, as the CYTO-PV trial demonstrated increased cardiovascular death and major thrombosis with higher targets 1.
Do not overlook infection as a cause of leukocytosis, even when erythrocytosis suggests a myeloproliferative disorder, as bacterial infection remains a critical differential requiring urgent treatment 4, 5.