Treatment of Essential Thrombocythemia
Treatment of essential thrombocythemia is risk-stratified, with high-risk patients (age >60 years, prior thrombosis, or JAK2 mutation with age >60) requiring cytoreductive therapy with hydroxyurea plus low-dose aspirin (81-100 mg/day), while low-risk patients are managed with aspirin alone or observation. 1, 2
Risk Stratification Framework
Essential thrombocythemia treatment depends entirely on thrombotic risk assessment, not platelet count alone 1, 2:
Very Low Risk
- Definition: Age ≤60 years, no JAK2 mutation, no prior thrombosis 1
- Management: Observation without cytoreductive therapy 1
Low Risk
- Definition: Age ≤60 years, JAK2 mutation present, no prior thrombosis 1
- Management: Low-dose aspirin 81-100 mg/day for microvascular symptoms (erythromelalgia, transient ischemic attacks) and aggressive cardiovascular risk factor management 1, 2
Intermediate Risk
- Definition: Age >60 years, no prior thrombosis, JAK2 wild-type 1
- Management: Low-dose aspirin plus consideration of cytoreductive therapy based on additional cardiovascular risk factors 1
High Risk
- Definition: Prior thrombosis at any age OR age >60 years with JAK2 mutation 1, 2
- Management: Low-dose aspirin (81-100 mg/day) PLUS cytoreductive therapy 1, 2
Primary Treatment Modalities
Low-Dose Aspirin
- Recommended at 81-100 mg/day for most patients to reduce thrombotic risk, particularly those with microvascular symptoms 2, 3
- In low-risk patients not taking aspirin, arterial thrombosis risk is 9.4/1000 patient-years and venous thrombosis risk is 8.2/1000 patient-years 3
- Critical caveat: Screen for acquired von Willebrand syndrome before initiating aspirin in patients with platelet counts >1,500 × 10⁹/L to avoid bleeding complications 2
Cytoreductive Therapy
- Hydroxyurea is the first-line cytoreductive agent for high-risk patients 1, 2, 4
- In a randomized trial of 114 high-risk patients, hydroxyurea significantly reduced thrombotic events compared to no cytoreduction (3.6% vs 24%; P < .01) 3
- Second-line option: Anagrelide for patients resistant or intolerant to hydroxyurea 4, 5
- Alternative for young patients or pregnancy: Interferon-alpha 4, 5
Special Populations
Pregnancy
- All pregnant women with essential thrombocythemia should receive aspirin therapy 2
- High-risk patients or those with recurrent fetal loss require interferon-alpha added to aspirin 2
- Hydroxyurea and anagrelide are contraindicated in pregnancy 6, 5
Extreme Thrombocytosis (>1,500 × 10⁹/L)
- Paradoxically increases bleeding risk due to acquired von Willebrand syndrome 2, 4
- Mandatory screening for acquired von Willebrand syndrome before aspirin initiation 2
- Consider cytoreductive therapy regardless of age if platelet count exceeds this threshold 5
Critical Treatment Pitfalls to Avoid
- Do not use therapeutic phlebotomy in essential thrombocythemia (unlike polycythemia vera) 1
- Avoid aspirin without von Willebrand screening when platelets >1,500 × 10⁹/L 2
- Do not delay cytoreductive therapy in high-risk patients - this increases thrombotic morbidity 1, 3
- Avoid anagrelide with other PDE3 inhibitors (cilostazol, milrinone) due to additive cardiovascular effects 6
- Monitor for bleeding when combining aspirin with anagrelide - observational data suggests higher major hemorrhagic event rates with this combination 6
Monitoring Requirements
- Regular complete blood counts to assess treatment response 2
- Surveillance for disease progression to myelofibrosis (occurs in
10% at 8.5 years) or acute myeloid leukemia (3% at 8.5 years) 3 - Bone marrow aspirate and biopsy before initiating cytoreductive therapy to rule out disease progression 1
- Cardiovascular risk factor assessment and aggressive management is mandatory for all patients 4, 3