Treatment of Essential Thrombocythemia
Treatment of essential thrombocythemia is determined by thrombotic risk stratification, with high-risk patients (age >60 years or prior thrombosis history) requiring cytoreductive therapy with hydroxyurea plus low-dose aspirin, while low-risk patients can be managed with aspirin alone. 1
Risk Stratification
The revised IPSET-Thrombosis model stratifies patients into four risk categories that guide treatment decisions 1:
- Very low risk: Age ≤60 years, no prior thrombosis, JAK2 wild-type
- Low risk: Age ≤60 years, no prior thrombosis, JAK2 mutation present
- Intermediate risk: Age >60 years, no prior thrombosis, no JAK2 mutation
- High risk: Prior thrombosis history at any age OR age >60 years with JAK2 mutation 1
Additional cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, smoking) must be aggressively managed in all patients, as these significantly increase arterial thrombosis risk 2, 3.
Treatment Algorithm by Risk Category
High-Risk Disease
All high-risk patients require cytoreductive therapy combined with antiplatelet therapy 1:
- First-line cytoreductive agent: Hydroxyurea, with goal platelet count <400-450 × 10⁹/L 2, 4
- Aspirin: 81-100 mg daily for vascular symptom prevention 1, 2
- Second-line options if hydroxyurea is not tolerated or patient is resistant:
The NCCN guidelines emphasize that hydroxyurea or interferons should be selected based on patient-specific variables, with interferons particularly preferred for younger patients or those of childbearing potential 1.
Low-Risk Disease
Low-risk patients (age ≤60 years, no thrombosis history, no cardiovascular risk factors, platelet count <1,500 × 10⁹/L) should receive low-dose aspirin 81-100 mg daily 2, 3. Observation alone without aspirin is an option, but aspirin is generally recommended given the demonstrated benefit in preventing thrombotic events 3.
Intermediate-Risk Disease
Intermediate-risk patients warrant consideration of cytoreductive therapy on a case-by-case basis 1. Treatment decisions should account for:
- Presence and severity of cardiovascular risk factors 2
- Degree of thrombocytosis (particularly if >1,500 × 10⁹/L) 6
- Presence of vasomotor symptoms despite aspirin 1
Low-dose aspirin should be initiated in all intermediate-risk patients unless contraindicated 2.
Special Considerations and Caveats
Extreme Thrombocytosis
Screen for acquired von Willebrand disease before initiating aspirin in patients with platelet counts >1,000 × 10⁹/L 2. Aspirin should be used with caution in these patients due to increased bleeding risk 1. However, this is not a concern for patients with platelet counts in the 500-700 × 10⁹/L range 2.
Pregnancy
Pregnant patients requiring cytoreductive therapy should receive interferon-α (interferon alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b), as this is the only safe cytoreductive option during pregnancy 1, 7. Hydroxyurea is contraindicated in pregnancy.
Platelet Count as Treatment Target
The absolute platelet count itself is not a strong predictor of thrombotic risk and should not be the sole driver of treatment decisions 8. The focus should be on risk stratification based on age, thrombosis history, and JAK2 mutation status rather than achieving specific platelet thresholds 8. However, cytoreductive therapy aims for platelet counts <400-450 × 10⁹/L when indicated 2.
Indications for Changing Cytoreductive Therapy
Consider switching cytoreductive agents if patients develop 1:
- Intolerance or resistance to hydroxyurea or interferon
- New thrombosis despite treatment
- Acquired von Willebrand disease or disease-related major bleeding
- Progressive splenomegaly or leukocytosis
- Vasomotor disturbances not responsive to aspirin
Monitoring Strategy
Complete blood counts should be monitored every 2-4 weeks initially, then every 4-12 weeks once stable 2. Annual bone marrow evaluation may be necessary to assess for disease progression to myelofibrosis 2. Patients should be monitored for new thrombosis, acquired von Willebrand disease, and disease-related bleeding 1.