What is the initial test order for a patient with polycythemia?

Initial Testing for Polycythemia

For a patient with high hemoglobin/polycythemia, the initial diagnostic workup should include complete blood count with peripheral blood smear, JAK2 V617F mutation testing, and serum erythropoietin level. 1

Diagnostic Approach

First-Line Testing

1. Complete Blood Count (CBC) with peripheral blood smear

   • Evaluates hemoglobin, hematocrit, red blood cell count, white blood cell count, and platelet count
   • Peripheral smear helps identify abnormal cell morphology
   • Look for elevated hemoglobin (>18.5 g/dL in men, >16.5 g/dL in women) or hematocrit (>49% in men, >48% in women) 1

2. JAK2 V617F mutation testing

   • Present in >95% of polycythemia vera cases 2
   • Helps distinguish between primary polycythemia (myeloproliferative neoplasm) and secondary causes
   • Essential for diagnosing masked polycythemia vera 1

3. Serum erythropoietin level

   • Low levels suggest primary polycythemia (PV)
   • Normal or elevated levels suggest secondary polycythemia 1

Second-Line Testing (if initial tests are inconclusive)

• JAK2 exon 12 mutation testing (if JAK2 V617F is negative but PV still suspected)
• Bone marrow biopsy and aspiration (to evaluate megakaryocyte morphology and clustering, assess for reticulin fibrosis) 1
• Arterial blood gas analysis (to rule out hypoxic causes)
• Abdominal ultrasound (to evaluate for splenomegaly)

Differential Diagnosis

Primary Polycythemia

• Polycythemia vera (PV) - a myeloproliferative neoplasm characterized by increased red blood cell mass and JAK2 mutation 2

Secondary Polycythemia

1. Hypoxia-driven causes:

   • Chronic pulmonary disease
   • Sleep apnea
   • High altitude
   • Smoking
   • Congenital heart disease

2. Non-hypoxia-driven causes:

   • Renal cell carcinoma
   • Uterine leiomyoma
   • Pheochromocytoma
   • Meningioma 1

3. Relative polycythemia:

   • Dehydration
   • Diuretic use
   • Stress polycythemia (Gaisböck syndrome) 1

Clinical Pearls and Pitfalls

Important Clinical Features to Note

• Pruritus (especially after warm shower)
• Erythromelalgia (burning pain in extremities)
• Transient visual changes
• Splenomegaly with abdominal discomfort
• History of unusual thrombosis (especially splanchnic vein thrombosis) 2

Common Pitfalls

• Overlooking masked PV: Iron deficiency can normalize hemoglobin in PV patients 1
• Missing secondary causes: When JAK2 mutation is absent, secondary causes must be thoroughly investigated 1
• Neglecting relative polycythemia: Dehydration, diuretics, or smoking can cause relative polycythemia 1
• Failing to recognize early PV: Cases with borderline elevated counts but with PV-related features may be missed 1

Management Considerations

If polycythemia vera is diagnosed:

• Therapeutic phlebotomy (goal hematocrit <45%)
• Low-dose aspirin (if no contraindications)
• Risk stratification for consideration of cytoreductive therapy 2, 3

Remember that untreated patients with PV may survive only 6-18 months, whereas adequate treatment can extend life expectancy to more than 10 years 4. Therefore, prompt and accurate diagnosis is essential for improving outcomes.