What is the management of essential thrombocytosis?

Management of Essential Thrombocythemia

The management of essential thrombocythemia (ET) should be risk-stratified, with low-dose aspirin (81-100 mg/day) recommended for most patients and cytoreductive therapy reserved for high-risk patients. 1

Risk Stratification

Essential thrombocythemia risk is categorized into four groups based on the revised International Prognostic Score of Thrombosis for ET (IPSET-Thrombosis):

• Very low risk: Age ≤60 years, no JAK2 mutation, no prior history of thrombosis
• Low risk: Age ≤60 years, with JAK2 mutation, no prior history of thrombosis
• Intermediate risk: Age >60 years, no JAK2 mutation, no prior history of thrombosis
• High risk: History of thrombosis at any age OR age >60 years with JAK2 mutation 1

Management Algorithm

Very Low-Risk and Low-Risk Patients

• Primary management: Observation or low-dose aspirin (81-100 mg/day) for vascular symptoms 1
• Monitoring: Regular assessment for new thrombosis, acquired von Willebrand disease (VWD), and/or disease-related major bleeding
• Cardiovascular risk factor management: Aggressive control of hypertension, diabetes, hyperlipidemia, and smoking cessation
• Indications for cytoreductive therapy:
  • Symptomatic thrombocytosis
  • Progressive leukocytosis
  • Progressive disease-related symptoms (pruritus, night sweats, fatigue)
  • Vasomotor/microvascular disturbances not responsive to aspirin 1

High-Risk Patients

• Primary management: Cytoreductive therapy PLUS low-dose aspirin (81-100 mg/day) 1
• First-line cytoreductive options:
  • Hydroxyurea (most commonly used)
  • Interferons (preferred in younger patients or pregnant women) 1, 2
• Second-line cytoreductive options:
  • Anagrelide (for patients intolerant or resistant to hydroxyurea) 1, 3

Special Considerations

Extreme Thrombocytosis (>1,000 × 10⁹/L)

• Associated with immediate risk of major hemorrhage but paradoxically lower risk of thrombosis 1
• Use aspirin with caution due to risk of acquired von Willebrand disease
• Consider cytoreductive therapy if symptomatic 1

Pregnancy

• Interferons are preferred if cytoreductive therapy is needed 4
• Low-dose aspirin can be continued during pregnancy if platelet count <1,500 × 10⁹/L 4

Perioperative Management

• Consider platelet count thresholds for procedures:
  • Major surgery: >50 × 10⁹/L
  • Neurosurgery: >100 × 10⁹/L 5

Monitoring Recommendations

• Regular assessment of blood counts and symptoms
• Bone marrow aspirate and biopsy should be performed to rule out disease progression to myelofibrosis prior to initiating cytoreductive therapy 1
• Monitor for transformation to myelofibrosis (occurs in approximately 10% of patients at 8.5 years) or acute myeloid leukemia (occurs in approximately 3% of patients) 2

Medication Considerations

Hydroxyurea

• First-line cytoreductive agent for high-risk patients
• In a randomized trial of high-risk patients, hydroxyurea significantly lowered thrombotic events compared to no cytoreductive therapy (3.6% vs 24%) 2

Anagrelide

• Second-line therapy for patients resistant or intolerant to hydroxyurea 1, 6
• Caution: May cause cardiac side effects including tachycardia, palpitations, and QT prolongation
• Avoid in patients taking medications that prolong QT interval 3
• Monitor for adverse effects: headache, palpitations, diarrhea, fluid retention, heart failure, and arrhythmias 3

Aspirin

• Low-dose aspirin (81-100 mg/day) reduces risk of thrombotic complications 1
• Use with caution in patients with extreme thrombocytosis (>1,000 × 10⁹/L) due to risk of acquired von Willebrand disease and bleeding 1
• Higher-dose aspirin may be appropriate in selected patients with vasomotor symptoms 1

Disease Monitoring and Progression

• Regular monitoring for signs of disease progression
• Approximately 10% of patients develop myelofibrosis and about 3% develop acute myeloid leukemia at a median of 8.5 years from diagnosis 2
• Leukemic transformation rate at 10 years is <1% but might be higher in JAK2-mutated patients with extreme thrombocytosis 7

Common Pitfalls to Avoid

• Failure to assess thrombotic risk factors
• Inappropriate use of aspirin in patients with extreme thrombocytosis and acquired VWD
• Inadequate monitoring for disease progression
• Overlooking cardiovascular risk factor management
• Failure to adjust therapy based on changing risk profiles over time

By following this risk-stratified approach to management, the morbidity and mortality associated with thrombotic and hemorrhagic complications of essential thrombocythemia can be significantly reduced.