What is the treatment for essential thrombocytosis (ET)?

Treatment of Essential Thrombocythemia

The treatment of essential thrombocythemia (ET) should be risk-stratified, with cytoreductive therapy (hydroxyurea or anagrelide) plus low-dose aspirin recommended for high-risk patients, while observation or aspirin alone is appropriate for lower-risk patients. 1

Risk Stratification

Treatment decisions for ET should be based on thrombotic risk assessment using the revised IPSET-Thrombosis classification:

• 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 JAK2 mutation, no prior thrombosis
• High Risk: Prior history of thrombosis at any age OR age >60 years with JAK2 mutation

Treatment Algorithm by Risk Category

Very Low-Risk and Low-Risk ET

• Observation is appropriate for asymptomatic very low-risk patients
• Aspirin (81-100 mg/day) may be considered for low-risk patients, especially those with JAK2 mutations or cardiovascular risk factors 1, 2
• Monitor for: new thrombosis, acquired von Willebrand disease (VWD), and disease-related bleeding
• Caution: Aspirin should be used carefully in patients with platelet counts >1,000×10^9/L or with CALR mutations due to increased bleeding risk 3

Intermediate-Risk ET

• Aspirin (81-100 mg/day) is recommended 1
• Consider twice-daily aspirin in selected patients with inadequate 24-hour platelet inhibition 3
• Monitor for disease progression and indications for cytoreductive therapy

High-Risk ET

• Cytoreductive therapy plus aspirin (81-100 mg/day) is the standard treatment 1
• First-line cytoreductive options:
  • Hydroxyurea: Most established agent with proven efficacy in preventing thrombotic complications 1, 2
  • Anagrelide: Alternative option, particularly effective for platelet reduction 1, 4
• Alternative options for younger patients, pregnant patients, or those who cannot tolerate hydroxyurea:
  • Interferon alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b 1

Special Considerations

Monitoring Response

• Evaluate symptom status using MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
• Assess for signs of disease progression every 3-6 months
• Monitor complete blood counts regularly
• Bone marrow examination as clinically indicated 1

Indications for Changing Therapy

• New thrombosis or major bleeding
• Intolerance or resistance to current therapy
• Symptomatic or progressive splenomegaly
• Symptomatic thrombocytosis
• Progressive leukocytosis
• Worsening disease-related symptoms (pruritus, night sweats, fatigue)
• Vasomotor/microvascular disturbances not responsive to aspirin 1

Hydroxyurea Resistance/Intolerance

Consider alternative therapy if any of the following occur:

• Platelet count >600×10^9/L and WBC <2.5×10^9/L at any dose
• Platelet count >400×10^9/L and hemoglobin <10 g/dL at any dose
• Presence of leg ulcers or other unacceptable mucocutaneous manifestations
• Hydroxyurea-related fever 1

Practical Considerations

• Aspirin formulation: Plain aspirin is preferred over enteric-coated aspirin due to better absorption and efficacy 3
• Aspirin dosing: Twice-daily aspirin (81-100 mg twice daily) may provide better 24-hour platelet inhibition in patients with high platelet counts 3
• Pregnancy: Interferon is the preferred cytoreductive agent for pregnant patients requiring treatment 1
• Referral: Consultation with specialists experienced in managing myeloproliferative neoplasms is strongly recommended for all ET patients 1

Remember that the primary goal of ET treatment is to prevent thrombotic and hemorrhagic complications while minimizing treatment-related toxicity and preserving quality of life.