What is the workup for thrombocytosis (elevated platelet count)?

Workup for Elevated Platelets (Thrombocytosis)

The workup for thrombocytosis should first distinguish between primary (clonal) and secondary (reactive) causes through a structured diagnostic approach including complete blood count with peripheral smear, inflammatory markers, iron studies, JAK2 mutation testing, and bone marrow examination in selected cases. 1

Initial Assessment

Definition and Classification

• Thrombocytosis: platelet count >450 × 10^9/L 2
• Two main categories:
  • Primary (clonal) thrombocytosis (12.5% of cases) 2
    • Myeloproliferative neoplasms (MPNs)
    • Essential thrombocythemia
    • Polycythemia vera
    • Primary myelofibrosis
  • Secondary (reactive) thrombocytosis (83.1% of cases) 2
    • Tissue injury (32.2%)
    • Infection (17.1%)
    • Chronic inflammatory disorders (11.7%)
    • Iron deficiency anemia (11.1%)

Clinical Evaluation

• Assess for symptoms of thrombosis or bleeding
• Evaluate for underlying conditions:
  • Recent surgery or trauma
  • Active infection or inflammation
  • Malignancy
  • Splenectomy history
  • Medication review (corticosteroids, epinephrine)
  • Bleeding or bruising (paradoxically seen with extreme thrombocytosis)

Diagnostic Algorithm

Step 1: Initial Laboratory Tests

• Complete blood count with differential
• Peripheral blood smear examination
• Inflammatory markers (ESR, CRP)
• Iron studies (serum iron, ferritin, TIBC)
• Liver function tests
• Renal function tests

Step 2: Exclude Pseudothrombocytosis

• Collect blood in a tube containing sodium citrate to rule out EDTA-induced platelet clumping 3

Step 3: Evaluate for Secondary Causes

• If inflammatory markers elevated: consider infection, inflammation, malignancy
• If ferritin low/TIBC high: consider iron deficiency
• If abnormal liver function: consider hepatic disease
• Review medication history for drugs that may cause thrombocytosis

Step 4: Molecular and Specialized Testing

If secondary causes excluded or clinical suspicion for MPN:

• JAK2 V617F mutation testing (positive in ~60% of essential thrombocythemia) 4
• If JAK2 negative: test for CALR and MPL mutations
• Consider bone marrow aspiration and biopsy with cytogenetic studies

Risk Assessment

Thrombotic Risk Stratification in Primary Thrombocytosis

• High risk: age >60 years, history of thrombosis, JAK2 mutation positive 1
• Low risk: absence of above risk factors

Bleeding Risk Assessment

• Extreme thrombocytosis (>1,000 × 10^9/L) may paradoxically increase bleeding risk due to acquired von Willebrand syndrome 1, 5

Management Considerations

For primary thrombocytosis:

• High-risk patients: cytoreductive therapy (hydroxyurea) to target platelet count <400 × 10^9/L 1
• Low-dose aspirin (81-100 mg/day) for vascular symptoms 1
• Consider interferons in younger patients or pregnant women 1

For secondary thrombocytosis:

• Treat underlying cause
• Thromboprophylaxis generally not required unless additional risk factors present

Monitoring

• Regular complete blood counts to assess response to therapy
• Evaluate for disease progression or development of complications
• Monitor for symptoms of thrombosis or bleeding

Common Pitfalls to Avoid

• Failing to distinguish between primary and secondary thrombocytosis
• Overlooking extreme thrombocytosis (>1,000 × 10^9/L) as a potential cause of bleeding
• Initiating cytoreductive therapy for secondary thrombocytosis
• Missing underlying malignancy as a cause of thrombocytosis
• Neglecting to test for JAK2 and other driver mutations when primary thrombocytosis is suspected

Remember that while secondary thrombocytosis is more common, primary thrombocytosis carries a higher risk of thrombotic complications and requires specific management strategies 2, 6.