What is the diagnosis and treatment for a patient with erythrocytosis, hyperhemoglobinemia, and elevated basophil percentage?

Diagnosis and Management of Erythrocytosis with Elevated Basophils

The patient's laboratory findings are most consistent with polycythemia vera (PV), which requires phlebotomy as first-line treatment to reduce hematocrit below 45% and consideration of cytoreductive therapy with hydroxyurea for high-risk patients. 1, 2

Laboratory Interpretation and Diagnosis

The patient presents with significant erythrocytosis as evidenced by:

• Elevated RBC (6.20 × 10^6/μL)
• Elevated hemoglobin (18.3 g/dL)
• Elevated hematocrit (55.1%)
• Elevated basophil percentage (1.2%)
• Normal platelet count (412 × 10^3/μL)

These findings strongly suggest polycythemia vera (PV), a myeloproliferative neoplasm characterized by increased red cell mass and the presence of JAK2 mutations in approximately 95% of cases. 1

Diagnostic Criteria for PV

According to the WHO diagnostic criteria, PV diagnosis requires either:

1. Both major criteria plus at least one minor criterion, OR
2. First major criterion plus at least two minor criteria 1

Major criteria:

• Elevated hemoglobin (>16.5 g/dL in women, >18.5 g/dL in men) or hematocrit (>49% in women, >52% in men)
• Presence of JAK2V617F or similar JAK2 mutation

Minor criteria:

• Bone marrow histology consistent with myeloproliferative neoplasm
• Subnormal serum erythropoietin level
• Endogenous erythroid colony formation

The patient meets the first major criterion with hemoglobin of 18.3 g/dL and hematocrit of 55.1%. JAK2 mutation testing is recommended to confirm the diagnosis. 1, 3

Management Approach

First-Line Treatment

1. Phlebotomy:

   • Target hematocrit <45% to reduce thrombotic risk
   • Initial frequency may be weekly until target achieved
   • Maintenance phlebotomy schedule based on hematocrit levels 4

2. Risk Stratification:

   • High risk: Age >60 years OR history of thrombosis
   • Low risk: Age <60 years AND no history of thrombosis 4

Additional Therapy Based on Risk

• High-risk patients: Add cytoreductive therapy with hydroxyurea (starting dose 15-20 mg/kg/day) 2
• Low-risk patients with significant thrombocytosis, leukocytosis, or symptomatic splenomegaly: Consider hydroxyurea 2, 4

Monitoring

• Complete blood count every 2-4 weeks initially, then every 3-6 months once stable
• Monitor for symptoms of hyperviscosity (headache, dizziness, visual disturbances)
• Assess for splenomegaly at each visit
• Evaluate for thrombotic and hemorrhagic complications 5

Special Considerations

Hydroxyurea Administration

• Starting dose: 15 mg/kg/day (based on actual or ideal weight, whichever is less)
• Reduce dose by 50% if creatinine clearance <60 mL/min
• Monitor for myelosuppression with weekly blood counts initially
• Dose adjustments based on blood counts and clinical response 2

Potential Complications

1. Thrombosis: Most significant cause of morbidity and mortality in PV
2. Bleeding: Can occur despite elevated platelet count due to platelet dysfunction
3. Disease progression: Risk of transformation to myelofibrosis or acute leukemia
4. Hydroxyurea side effects: Myelosuppression, gastrointestinal symptoms, skin ulcers, cutaneous vasculitis 2

Important Pitfalls to Avoid

1. Misdiagnosis as secondary erythrocytosis: Always exclude secondary causes (hypoxia, renal disease, EPO-producing tumors)
2. Overlooking "masked PV": Some patients may not meet strict hemoglobin/hematocrit thresholds but still have PV 6
3. Inadequate hematocrit control: Failure to maintain hematocrit <45% increases thrombotic risk
4. Missing concomitant iron deficiency: Can mask the degree of erythrocytosis 7

Follow-up Recommendations

• JAK2 mutation testing to confirm diagnosis
• Serum erythropoietin level to help exclude secondary causes
• Bone marrow biopsy if diagnosis remains uncertain
• Consider screening for thrombophilia in patients with history of thrombosis
• Evaluate iron stores, especially if frequent phlebotomy is required 5, 3

The management of PV focuses on preventing thrombotic complications through hematocrit control while minimizing treatment-related adverse effects. Regular monitoring and appropriate risk-adapted therapy are essential for optimal outcomes.