What is the recommended treatment for high-risk primary thrombocytosis?

Treatment of High-Risk Primary Thrombocytosis

Hydroxyurea plus low-dose aspirin is the recommended first-line treatment for high-risk primary thrombocytosis to reduce thrombotic complications and improve survival. 1

Risk Stratification

High-risk primary thrombocytosis patients are defined as:

• Age >60 years and/or
• History of prior thrombosis

First-Line Treatment Algorithm

1. Cytoreductive therapy with hydroxyurea

   • Initial dosage: 500 mg twice daily orally 1
   • Target: Platelet count <400 × 10⁹/L 1
   • Monitor: Complete blood counts every 2-4 weeks initially, then every 3 months once stable

2. Add low-dose aspirin (81-100 mg daily) 1, 2

   • Contraindicated if platelet count >1,500 × 10⁹/L or history of major bleeding
   • Reduces risk of arterial thrombosis and cardiovascular events

3. Treatment response evaluation

   • Complete response: Platelet count <400 × 10⁹/L, WBC <10 × 10⁹/L, no disease-related symptoms 1, 2
   • Partial response: Platelet count reduction but not meeting complete response criteria

Second-Line Options

If hydroxyurea resistance or intolerance develops (defined as platelet count >600 × 10⁹/L despite adequate dosing, or development of unacceptable side effects), consider:

1. Interferon-α 1, 2

   • Preferred in younger patients (<40 years) and women of childbearing age
   • Initial dosage: 3 million units subcutaneously 3 times weekly
   • Advantage: Non-leukemogenic 1
   • Disadvantages: Flu-like symptoms, depression, subcutaneous administration

2. Anagrelide 3, 1

   • FDA-approved for thrombocythemia secondary to myeloproliferative neoplasms
   • Note: Less effective than hydroxyurea for arterial thrombosis prevention 4
   • Higher risk of transformation to myelofibrosis compared to hydroxyurea 4

Clinical Pearls and Pitfalls

• Multiple cytotoxic agents should be avoided as they significantly increase the risk of developing acute myeloid leukemia/myelodysplastic syndromes 1, 2

• Platelet count >1,500 × 10⁹/L is associated with increased bleeding risk and requires cytoreductive therapy even in otherwise low-risk patients 1, 2

• Hydroxyurea significantly reduces thrombotic events (HR 0.51) and improves overall survival (HR 0.52) in older patients with essential thrombocythemia 5

• Treatment efficacy monitoring should include normalization of blood counts and resolution of disease-related symptoms 1

• Leukocytosis is an independent risk factor for thrombosis and should be controlled with cytoreductive therapy 2

• Cardiovascular risk factors should be aggressively managed alongside cytoreductive therapy 1, 2

The evidence strongly supports hydroxyurea plus low-dose aspirin as the most effective regimen for high-risk primary thrombocytosis, with significant reductions in thrombotic complications and improved survival outcomes 6, 5, 4.