What is the first-line treatment for thrombocytosis (elevated platelet count)?

First-Line Treatment for Thrombocytosis

Hydroxyurea is the first-line cytoreductive therapy for thrombocytosis in high-risk patients and those with platelet counts exceeding 1,500 × 10⁹/L. 1, 2

Risk Stratification

Before initiating treatment, patients with thrombocytosis should be risk-stratified:

• Very low risk: Age ≤60 years, no JAK2 mutation, no prior thrombosis
• Low risk: Age ≤60 years, with JAK2 mutation, no prior thrombosis
• Intermediate risk: Age >60 years, no prior thrombosis
• High risk: Age >60 years and/or history of thrombosis 2, 3

Treatment Algorithm

For High-Risk Patients:

1. First-line therapy: Hydroxyurea (starting dose 500 mg twice daily) 1, 2
   • Target platelet count <400 × 10⁹/L
   • Add low-dose aspirin (81-100 mg daily)

For Low-Risk Patients:

1. Observation with regular monitoring
2. Low-dose aspirin if microvascular symptoms are present or JAK2V617F mutation is positive 1, 2

For All Patients with Platelet Count >1,500 × 10⁹/L:

• Initiate cytoreductive therapy regardless of risk category due to increased bleeding risk from acquired von Willebrand syndrome 1, 2, 4

Special Considerations

Monitoring Response:

• Complete response is defined as:
  • Platelet count <400 × 10⁹/L
  • WBC count <10 × 10⁹/L
  • No disease-related symptoms
  • No splenomegaly 1

Resistance or Intolerance to Hydroxyurea:

If the patient develops resistance or intolerance to hydroxyurea (defined by specific criteria including failure to reduce platelet count <600 × 10⁹/L after 3 months of adequate dosing, or development of leg ulcers/mucocutaneous manifestations), switch to:

1. Anagrelide (starting dose 0.5 mg four times daily or 1 mg twice daily) 1, 5
2. Interferon-α (particularly in younger patients <40 years and women of childbearing age) 1, 2

Important Cautions

• Avoid multiple cytotoxic agents simultaneously as this significantly increases the risk of developing acute myeloid leukemia/myelodysplastic syndromes 1, 6
• Use aspirin with caution in patients with platelet counts >1,500 × 10⁹/L due to increased bleeding risk 2
• Monitor for cardiovascular effects with anagrelide (QT prolongation, tachycardia) 5
• Consider hydroxyurea with caution in young patients (<40 years) due to long-term leukemogenic potential 1, 6

Efficacy and Outcomes

Hydroxyurea effectively reduces platelet counts to <500 × 10⁹/L within 8 weeks in approximately 80% of patients with essential thrombocythemia 7. Control of disease-related symptoms is typically achieved within 1 year in about 78% of patients 7. The goal of therapy is to prevent thrombotic complications, which hydroxyurea has been shown to do effectively compared to no treatment 1.

By following this risk-stratified approach to treatment, the risk of thrombotic and hemorrhagic complications can be significantly reduced while maintaining quality of life for patients with thrombocytosis.