What is the management for a patient with elevated red blood cell count, hemoglobin, and hematocrit levels, indicating polycythemia?

Management of Elevated Red Blood Cell Count, Hemoglobin, and Hematocrit

For a patient with RBC 5.7, hemoglobin 15.9, and hematocrit 50.3, the first step should be to determine whether this represents true polycythemia and if so, whether it is primary (polycythemia vera) or secondary polycythemia, as this will guide appropriate management.

Diagnostic Approach

Step 1: Confirm True Polycythemia

• Determine if these values represent true polycythemia versus relative polycythemia (plasma volume depletion)
• Check for common causes of relative polycythemia:
  • Dehydration
  • Diuretic use
  • Severe burns
  • Diarrhea/vomiting 1

Step 2: Evaluate for Polycythemia Vera (PV)

Apply WHO diagnostic criteria for PV 1:

Major criteria:

1. Hemoglobin >16.5 g/dL in men or >16.5 g/dL in women (or hematocrit >49% in men, >48% in women)
2. Presence of JAK2 V617F or other functionally similar mutation

Minor criteria:

1. Bone marrow biopsy showing hypercellularity with trilineage growth
2. Serum erythropoietin level below reference range
3. Endogenous erythroid colony formation in vitro

Diagnosis requires both major criteria and one minor criterion, or the first major criterion plus two minor criteria 1.

Step 3: Evaluate for Secondary Polycythemia

If JAK2 mutation is absent, investigate secondary causes:

Hypoxia-driven causes:

• Chronic lung disease
• Sleep apnea
• Smoking (carbon monoxide exposure)
• High altitude
• Congenital heart disease with right-to-left shunt 1

Non-hypoxic causes:

• Renal disease (renal cell carcinoma, renal artery stenosis)
• Hepatocellular carcinoma
• Endocrine disorders
• Exogenous erythropoietin or androgen use 1

Management Algorithm

For Polycythemia Vera:

1. All patients should receive:

   • Therapeutic phlebotomy to maintain hematocrit <45% 2
   • Low-dose aspirin (81 mg daily) if no contraindications 2, 3

2. Risk stratification:

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

3. For high-risk patients:

   • Add cytoreductive therapy:
     • First-line: Hydroxyurea
     • Second-line: Interferon-α or busulfan 3
   • Consider ruxolitinib for patients with severe pruritus or splenomegaly not responding to first-line therapy 3

For Secondary Polycythemia:

1. Treat the underlying cause when possible:

   • CPAP for sleep apnea
   • Smoking cessation
   • Treatment of underlying tumor or renal disease 1

2. Phlebotomy considerations:

   • For hypoxic conditions (COPD, cyanotic heart disease): Judicious phlebotomy to hematocrit 55-60% 1
   • For post-renal transplant erythrocytosis: Consider ACE inhibitors or angiotensin II receptor blockers 1

Monitoring and Follow-up

• Regular monitoring of complete blood count
• Assess for symptoms of hyperviscosity (headache, dizziness, visual disturbances)
• Monitor for thrombotic complications
• For PV patients: regular evaluation for disease progression to myelofibrosis or acute leukemia 2

Important Considerations

• Untreated polycythemia vera has poor survival (6-18 months), while proper treatment extends life expectancy to >10 years 4
• Avoid aggressive phlebotomy in patients with cyanotic heart disease due to risk of stroke 1
• Consider twice-daily aspirin dosing in patients with PV who have microvascular symptoms despite once-daily dosing 3
• Be aware that extreme thrombocytosis (platelets ≥1000 × 10^9/L) increases bleeding risk due to acquired von Willebrand disease 2