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

Workup and Management of Thrombocytosis

The appropriate workup for thrombocytosis begins with distinguishing between primary (clonal) and secondary (reactive) causes, as this fundamentally determines management approach and prognosis.

Initial Evaluation

• Complete blood count with peripheral blood smear to confirm thrombocytosis and evaluate for other cytopenias or abnormalities
• Evaluate peripheral blood smear to exclude pseudothrombocytosis and assess platelet morphology
• Comprehensive history and review of medications focusing on:
  • Recent infections
  • Iron deficiency
  • Inflammatory conditions
  • Malignancy
  • Recent surgery or trauma
  • Splenectomy
  • Medication use

Classification of Thrombocytosis

Secondary (Reactive) Thrombocytosis

• Most common form (>90% of cases)
• Common causes:
  • Infections (48% of pediatric cases) 1
  • Iron deficiency (24% of pediatric cases) 1
  • Inflammatory conditions
  • Post-surgical or post-traumatic
  • Malignancy
  • Post-splenectomy
  • Medications

Primary (Clonal) Thrombocytosis

• Myeloproliferative neoplasms:
  • Essential thrombocythemia
  • Polycythemia vera
  • Primary myelofibrosis
  • Chronic myeloid leukemia

Diagnostic Testing

First-line Tests

• Serum ferritin, iron studies (to rule out iron deficiency)
• Inflammatory markers (ESR, CRP)
• Liver function tests
• Renal function tests

Second-line Tests (if secondary causes excluded)

• JAK2V617F mutation testing (found in essential thrombocythemia, polycythemia vera) 2
• MPLW515L/K mutation testing 2
• Bone marrow examination with cytogenetic studies (key for diagnosis of myeloproliferative disorders) 2

Management Approach

Secondary Thrombocytosis

• Treatment of underlying cause is the primary approach 3
• Antiplatelet therapy is generally not warranted 3
• Thrombocytosis typically resolves with treatment of the underlying condition

Primary Thrombocytosis (Myeloproliferative Neoplasms)

Risk Stratification

• High risk: Age ≥60 years, history of thrombosis, or platelet count >1,500 × 10^9/L 4
• Low risk: Age <60 years, no history of thrombosis, no cardiovascular risk factors, platelet count <1,500 × 10^9/L 4
• Intermediate risk: Age <60 years, no thrombosis history, but with platelet count >1,500 × 10^9/L or significant cardiovascular risk factors 4

Treatment Options

1. High-risk patients:

   • Cytoreductive therapy with hydroxyurea 4
   • Alternatives: anagrelide or interferon-alpha if hydroxyurea not tolerated
   • Low-dose aspirin if platelet count <1,500 × 10^9/L

2. Low-risk patients:

   • Observation or low-dose aspirin 4

3. Intermediate-risk patients:

   • Treatment of cardiovascular risk factors
   • Consider observation, anagrelide, hydroxyurea, or interferon-alpha 4
   • Low-dose aspirin if platelet count <1,500 × 10^9/L

4. Anagrelide is FDA-approved for treatment of thrombocythemia secondary to myeloproliferative neoplasms:

   • Starting dose: 0.5 mg four times daily or 1 mg twice daily
   • Titrate to maintain target platelet counts
   • Maximum dose: 10 mg/day 5

Special Considerations

Pregnancy

• In pregnant women with myeloproliferative neoplasms:
  • Low-dose aspirin is recommended for ET patients with JAK2 mutation or cardiovascular risk factors 6
  • For high-risk pregnant patients requiring treatment, interferon-alpha is preferred 6
  • Hydroxyurea and warfarin are teratogenic and should be avoided 6

Thrombocytosis with Thrombocytopenia

• For patients with cancer and thrombocytopenia requiring anticoagulation:
  • Full-dose anticoagulation if platelet count >50 × 10^9/L 6
  • Half-dose anticoagulation if platelet count 20-50 × 10^9/L 6
  • Hold anticoagulation if platelet count <20 × 10^9/L 6

Monitoring

• Regular monitoring of platelet counts based on treatment approach
• For patients on cytoreductive therapy, monitor for side effects
• Assess for thrombotic or hemorrhagic complications

Common Pitfalls

• Failure to distinguish between primary and secondary thrombocytosis
• Unnecessary treatment of secondary thrombocytosis with antiplatelet agents
• Overlooking iron deficiency as a common cause of thrombocytosis
• Failure to recognize extreme thrombocytosis (>1,000 × 10^9/L) may be associated with acquired von Willebrand syndrome and bleeding risk

Remember that secondary thrombocytosis in children is benign and antiplatelet therapy is not necessary 6. The focus should be on identifying and treating the underlying cause rather than treating the elevated platelet count itself.