What laboratory tests should be ordered for a patient presenting with erythrocytosis (excess red blood cells)?

Laboratory Tests for Erythrocytosis Evaluation

The initial laboratory workup for erythrocytosis should include complete blood count (CBC), serum erythropoietin level, JAK2 mutation analysis, iron studies (ferritin and transferrin saturation), and renal function tests to differentiate between primary and secondary causes.

Initial Diagnostic Tests

First-Line Testing

• Complete Blood Count (CBC) with differential

  • Confirms true erythrocytosis (elevated hemoglobin/hematocrit)
  • Evaluates other cell lines for abnormalities (leukocytosis, thrombocytosis)
  • Assesses red cell indices (MCV, MCHC) for microcytosis or other abnormalities

• Serum Erythropoietin (EPO) Level

  • Critical for distinguishing primary from secondary erythrocytosis 1
  • Low EPO (<3.3 IU/L) is highly specific (97%) for polycythemia vera 2
  • Normal or elevated EPO suggests secondary erythrocytosis

• JAK2 Mutation Analysis

  • Test for JAK2V617F or exon 12 mutations
  • Positive result strongly indicates polycythemia vera 1, 3
  • Should be performed early in the diagnostic process

Second-Line Testing

• Iron Studies

  • Serum ferritin and transferrin saturation
  • Important to identify iron deficiency which may mask erythrocytosis 4, 5
  • Iron deficiency may occur in polycythemia vera due to phlebotomy

• Renal Function Tests

  • Creatinine and BUN
  • Evaluates for renal causes of erythrocytosis 4
  • Abnormal urate clearance is common in chronic cyanosis

Additional Testing Based on Initial Results

If Primary Erythrocytosis is Suspected (Low EPO and/or Positive JAK2)

• Bone Marrow Aspiration and Biopsy
  • Evaluates for hypercellularity and trilineage proliferation
  • Rules out other myeloproliferative disorders
  • Flow cytometry and cytogenetic testing to rule out lymphoproliferative disorders 4

If Secondary Erythrocytosis is Suspected (Normal/High EPO)

• Arterial Blood Gas Analysis

  • Evaluates for hypoxemia
  • Essential for identifying respiratory causes

• Pulmonary Function Tests

  • Identifies chronic lung disease as potential cause

• Echocardiogram

  • Evaluates for congenital heart disease with right-to-left shunting 4

• Sleep Study

  • Identifies obstructive sleep apnea as potential cause

• Abdominal Imaging

  • Ultrasound or CT scan to evaluate for renal masses or other tumors that may produce EPO

Special Considerations

For Congenital Erythrocytosis

• Hemoglobin Electrophoresis

  • Identifies high-oxygen-affinity hemoglobinopathies

• Genetic Testing

  • For EPO receptor mutations
  • Von Hippel-Lindau gene mutations
  • Other germline mutations affecting oxygen sensing 1

For Suspected Relative Erythrocytosis

• Plasma Volume Studies
  • Differentiates true erythrocytosis from apparent erythrocytosis due to plasma volume contraction

Interpretation Pitfalls

1. Iron Deficiency Masking

   • Iron deficiency can lower hemoglobin levels in polycythemia vera
   • Always check iron studies even with borderline hemoglobin values 4

2. EPO Level Interpretation

   • EPO levels may be normal in some cases of polycythemia vera (sensitivity ~70%)
   • Very low EPO (<1.4 IU/L) is highly specific for polycythemia vera 2
   • EPO >13.7 IU/L strongly suggests secondary erythrocytosis 2

3. Comorbid Conditions

   • A patient can have both polycythemia vera and an unrelated condition causing hypoxia 4
   • Comprehensive evaluation is necessary to identify all contributing factors

By following this systematic approach to laboratory testing for erythrocytosis, clinicians can efficiently differentiate between primary and secondary causes, leading to appropriate management strategies that will reduce morbidity and mortality associated with this condition.