What is the initial workup and treatment for a patient presenting with polycythemia?

Initial Workup and Treatment for Polycythemia

The initial workup for polycythemia should begin with determining serum erythropoietin (EPO) level, followed by bone marrow examination with cytogenetic studies to distinguish polycythemia vera (PV) from secondary causes of polycythemia. 1

Diagnostic Approach

Step 1: Suspect Polycythemia

Consider polycythemia when:

• Hemoglobin/hematocrit is higher than the 95th percentile for sex and race
• Documented increase in hemoglobin/hematocrit above patient's baseline
• PV-related features (thrombocytosis, leukocytosis, microcytosis, splenomegaly, aquagenic pruritus, unusual thrombosis, erythromelalgia) with borderline-high hematocrit 1

Step 2: Initial Laboratory Tests

• Complete blood count with differential
• Serum erythropoietin (EPO) level
  • Low EPO: Highly suggestive of PV (specificity >90%)
  • Normal EPO: PV still possible (sensitivity of low EPO for PV <70%)
  • High EPO: PV unlikely, suggests secondary polycythemia 1

Step 3: Additional Testing

• Bone marrow examination with cytogenetic studies
  • PV findings: Hypercellularity, increased megakaryocytes with clustering, giant megakaryocytes, mild reticulin fibrosis (12%), decreased iron stores 1
• JAK2V617F mutation testing (present in >95% of PV cases) 2
• If JAK2V617F negative, test for calreticulin mutation 1
• For suspected secondary polycythemia:
  • Arterial blood gas (oxygen saturation)
  • Carboxyhemoglobin level (especially in smokers)
  • Sleep study (if sleep apnea suspected)
  • P50 test (if congenital cause suspected)
  • Renal/abdominal imaging (if renal disease or tumor suspected) 1

Treatment Approach

For Polycythemia Vera

All Patients:

• Therapeutic phlebotomy to maintain hematocrit <45% 2, 3
• Low-dose aspirin (81mg daily) unless contraindicated 2, 3

Risk Stratification:

• High risk: Age >60 years OR history of thrombosis
• Low risk: Absence of both risk factors 3, 4

Treatment by Risk Category:

• High-risk patients: Add cytoreductive therapy

  • First-line: Hydroxyurea (starting dose 15-20mg/kg/day) 1, 3, 5
  • Second-line options: Interferon-α or busulfan 3
  • Consider ruxolitinib for severe pruritus or splenomegaly not responding to other treatments 3

• Low-risk patients with symptoms: Consider cytoreductive therapy if persistent symptoms or high phlebotomy requirements 4

For Secondary Polycythemia:

• Treat underlying cause (e.g., smoking cessation, CPAP for sleep apnea)
• For hypoxia-driven polycythemia: Avoid aggressive phlebotomy due to risk of stroke 1
• For polycythemia with splanchnic vein thrombosis: Consider long-term anticoagulation 1

Special Considerations

Monitoring:

• Regular CBC to assess disease control
• Monitor for thrombotic and hemorrhagic complications
• Watch for disease progression to myelofibrosis (12.7%) or acute myeloid leukemia (6.8%) 2

Complications to Watch For:

• Thrombosis: Most common in unusual sites (splanchnic veins, cerebral sinuses)
• Bleeding: Especially with extreme thrombocytosis (≥1000 × 10^9/L) due to acquired von Willebrand disease 2
• Pruritus: Consider paroxetine (selective serotonin reuptake inhibitor) for intractable cases 1

Common Pitfalls:

• Relying solely on hematocrit without considering other PV features
• Overlooking secondary causes of polycythemia
• Measuring red cell mass (RCM) is rarely necessary and can be misleading 1
• Failure to test for JAK2 mutation in patients with normal blood counts but suspected PV 1

By following this structured approach to diagnosis and treatment, mortality and morbidity from thrombotic complications can be significantly reduced while maintaining quality of life for patients with polycythemia.