Management of Essential Erythrocytosis (Essential Thrombocythemia)
The management of essential thrombocythemia (ET) should be risk-stratified, with low-dose aspirin and cytoreductive therapy as the cornerstones of treatment for high-risk patients to prevent thrombohemorrhagic complications. 1
Risk Stratification
Risk stratification is crucial for determining appropriate treatment strategies:
Risk Categories for ET:
- Very Low Risk: Age ≤60 years, no JAK2 mutation, no prior thrombosis history 1
- Low Risk: Age ≤60 years, with JAK2 mutation, no prior thrombosis history 1
- Intermediate Risk: Age >60 years, no prior thrombosis history, JAK2 wild-type 1
- High Risk: Prior thrombosis history at any age OR age >60 years with JAK2 mutation 1
Additional risk factors to consider:
- Leukocytosis (>11 × 10^9/L) 1
- Cardiovascular risk factors 1
- Extreme thrombocytosis (>1,000 × 10^9/L) may paradoxically increase bleeding risk due to acquired von Willebrand syndrome 2, 3
Treatment Approach
Very Low-Risk ET:
- Observation without cytoreductive therapy 1
- Monitor for new thrombosis, acquired von Willebrand disease, and/or disease-related major bleeding 1
Low-Risk ET:
- Low-dose aspirin (81-100 mg/day) for vascular symptoms 1
- Manage cardiovascular risk factors 1
- Observation without aspirin may be considered in CALR-mutated cases 1
Intermediate-Risk ET:
High-Risk ET:
- Low-dose aspirin (81-100 mg/day) 1
- Cytoreductive therapy is recommended 1
- First-line: Hydroxyurea 1
- Second-line options (for hydroxyurea intolerance/resistance): Interferon-α or busulfan 2, 4
- Anagrelide is an alternative second-line option 5
Special Considerations
Extreme Thrombocytosis (>1,000 × 10^9/L):
- Screen for acquired von Willebrand syndrome before administering aspirin 3, 5
- Consider cytoreductive therapy to reduce bleeding risk 1, 3
Progressive Disease Symptoms:
Indications for changing cytoreductive therapy include:
- New thrombosis 1
- Symptomatic or progressive splenomegaly 1
- Progressive leukocytosis 1
- Progressive disease-related symptoms (pruritus, night sweats, fatigue) 1
- Vasomotor/microvascular disturbances not responsive to aspirin 1
Thrombocytopenia During Treatment:
If thrombocytopenia develops during treatment:
- For platelet counts ≥50 × 10^9/L: Continue full therapeutic anticoagulation if needed 1
- For platelet counts 25-50 × 10^9/L: Reduce anticoagulant dose to 50% or use prophylactic dose 1
- For platelet counts <25 × 10^9/L: Consider temporarily discontinuing anticoagulation 1
Monitoring Requirements:
- Regular complete blood counts 1
- Monitor for disease progression to myelofibrosis or acute leukemia 1, 2
- Bone marrow aspirate and biopsy should be performed to rule out disease progression before initiating cytoreductive therapy 1
Potential Complications and Management
Thrombotic Complications:
- Most common major complication (risk exceeds 20% over time) 3
- Higher risk in JAK2-mutated cases 1, 4
- Maintain strict control of cardiovascular risk factors 5
Bleeding Complications:
- Associated with extreme thrombocytosis (>1,000 × 10^9/L) due to acquired von Willebrand syndrome 3
- Use aspirin with caution in patients with acquired von Willebrand disease 1
Disease Progression:
- 10-year risk of leukemic transformation: <1% 2, 4
- 10-year risk of progression to myelofibrosis: approximately 1% 2, 4
Treatment Pitfalls to Avoid
- Do not use therapeutic phlebotomy in ET (unlike in polycythemia vera) 1
- Avoid inappropriate aspirin use in patients with extreme thrombocytosis without screening for acquired von Willebrand syndrome 1, 3
- Do not delay cytoreductive therapy in high-risk patients 1
- Avoid using ruxolutinib as first-line therapy 2, 4
- Do not perform routine, inappropriate phlebotomies that could lead to iron deficiency 1