Treatment of Essential Thrombocythemia
Treatment for essential thrombocythemia is determined by thrombotic risk stratification, with high-risk patients requiring cytoreductive therapy plus aspirin, while low-risk patients may be managed with aspirin alone. 1
Risk Stratification
The revised IPSET-Thrombosis model stratifies patients into four risk categories based on age, thrombosis history, and JAK2 mutation status 1:
- Very low risk: Age ≤60 years, no prior thrombosis, JAK2 wild-type 1
- Low risk: Age ≤60 years, no prior thrombosis, JAK2 mutation present 1
- Intermediate risk: Age >60 years, no prior thrombosis, no JAK2 mutation 1
- High risk: Prior thrombosis at any age OR age >60 years with JAK2 mutation 1
Treatment Algorithm
High-Risk Patients
High-risk patients require cytoreductive therapy combined with antiplatelet therapy. 1
First-line cytoreductive therapy:
- Hydroxyurea is the preferred first-line agent 1, 2, 3
- Starting dose adjusted to blood counts with goal platelet count <400-450 × 10⁹/L 2
- Aspirin 81-100 mg daily for vascular symptom prevention 1, 2
Second-line options when hydroxyurea is not tolerated:
- Interferons (interferon alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b) - particularly preferred for younger patients 1, 2
- Anagrelide as an alternative cytoreductive agent 1, 4
Low-Risk and Intermediate-Risk Patients
Low-dose aspirin (81-100 mg daily) is recommended for all patients without contraindications. 2, 5
- Low-risk patients can be managed with aspirin alone 1, 5
- Intermediate-risk patients may be observed with aspirin or considered for cytoreductive therapy based on additional risk factors 1
Important Caveats and Monitoring
Aspirin Considerations
Aspirin should be used with caution in patients with extreme thrombocytosis (>1,000-1,500 × 10⁹/L) due to acquired von Willebrand disease risk. 1, 2
- Screen for acquired von Willebrand disease before initiating aspirin in patients with extreme thrombocytosis 2
- Higher-dose aspirin may be appropriate in selected patients with vasomotor symptoms, weighing bleeding risk 1
Cardiovascular Risk Factor Management
All modifiable cardiovascular risk factors must be aggressively managed, including blood pressure, glucose control, lipid management, and smoking cessation. 2
Monitoring Schedule
- Complete blood count every 2-4 weeks initially, then every 4-12 weeks once stable 2
- Annual bone marrow evaluation if necessary to rule out disease progression 2
- Monitor for thrombosis, acquired von Willebrand disease, and disease-related bleeding 1
Indications for Changing Cytoreductive Therapy
Consider switching agents if patients develop 1:
- Intolerance or resistance to hydroxyurea or interferon
- New thrombosis despite treatment
- Symptomatic or progressive splenomegaly
- Progressive leukocytosis
- Vasomotor disturbances not responsive to aspirin (headaches, chest pain, erythromelalgia)
Special Populations
For pregnant patients requiring cytoreductive therapy, interferons are preferred over hydroxyurea. 1
- Avoid estrogen-containing contraceptives; prefer non-hormonal or progesterone-based options 2
Disease Progression
Monitor for transformation to myelofibrosis (approximately 10% at 10 years) or acute myeloid leukemia (approximately 3% at 10 years). 5 Perform bone marrow biopsy to rule out progression to myelofibrosis prior to initiating cytoreductive therapy. 1
Common Pitfall
The platelet count itself is not a reliable predictor of thrombotic risk - higher platelet counts correlate more clearly with bleeding risk than thrombosis risk. 6 Treatment decisions should be based on the risk stratification model, not absolute platelet number alone.