Management of Very Low Risk Essential Thrombocythemia
Primary Recommendation
For very low-risk ET patients (age ≤60 years, no JAK2 mutation, no prior thrombosis), observation without any treatment is the recommended approach—no aspirin and no cytoreductive therapy are indicated. 1
Risk Stratification Framework
The revised IPSET-Thrombosis score defines very low-risk ET by three specific criteria that must all be present: 1, 2
- Age ≤60 years
- Absence of JAK2 V617F mutation (JAK2 wild-type)
- No prior history of thrombosis
This risk category was specifically delineated to identify patients whose thrombotic risk approximates that of the general population, with an incidence of 1.91 thrombotic events per 100 patient-years compared to 1.50 in age-matched controls. 3
Treatment Strategy
Observation Without Intervention
Very low-risk patients should be monitored without initiating any pharmacologic therapy. 1 This conservative approach is supported by prospective data demonstrating no increased thrombotic risk compared to healthy controls when platelet counts remain below 1,500 × 10⁹/L. 3
When NOT to Use Aspirin
Aspirin is not recommended for asymptomatic very low-risk ET patients. 1, 4 The absence of JAK2 mutation in this population means lower thrombotic risk, and retrospective analyses suggest aspirin may increase bleeding risk without reducing thrombosis in CALR-mutated patients. 1
Monitoring Requirements
Regular surveillance should focus on: 1, 4
- Complete blood counts to track platelet trends and detect progression
- New thrombotic events (arterial or venous)
- Acquired von Willebrand disease (particularly if platelets exceed 1,000 × 10⁹/L)
- Disease-related major bleeding
- Cardiovascular risk factors that may shift risk category
Indications to Escalate Therapy
Treatment should be initiated if any of the following develop: 1
- New thrombotic event (arterial or venous)—immediately start aspirin and cytoreductive therapy
- Microvascular symptoms (erythromelalgia, transient neurologic symptoms, headaches)—start aspirin 81-100 mg daily 1
- Symptomatic or progressive splenomegaly—consider cytoreductive therapy
- Platelet count exceeding 1,500 × 10⁹/L—initiate cytoreductive therapy due to hemorrhagic risk 1
- Progressive leukocytosis or disease-related symptoms (pruritus, night sweats, fatigue)—consider cytoreductive therapy 1
- Reaching age 60 years—automatically shifts to intermediate-risk category requiring aspirin 1, 2
Critical Distinctions from Low-Risk ET
The presence of JAK2 mutation fundamentally changes management. Low-risk ET patients (age ≤60, JAK2-mutated, no prior thrombosis) should receive aspirin 81-100 mg daily, whereas very low-risk patients (JAK2 wild-type) should not. 1, 4 This distinction reflects the higher thrombotic risk conferred by JAK2 mutation even in younger patients without prior events. 1, 2
Common Pitfalls to Avoid
Do not reflexively prescribe aspirin based solely on elevated platelet count. 1, 4 The platelet count itself (even 600-800 × 10⁹/L) does not mandate treatment in very low-risk patients without symptoms or JAK2 mutation. 3, 5
Do not initiate cytoreductive therapy for asymptomatic very low-risk disease. 1 Hydroxyurea and other cytoreductive agents carry leukemogenic risk and should be reserved for patients who develop high-risk features or symptomatic disease. 1
Ensure bone marrow biopsy has excluded prefibrotic myelofibrosis. 1, 6 This diagnosis masquerading as ET would require different management and has worse prognosis.
Pregnancy and Surgery Considerations
Pregnancy and surgery are not associated with increased thrombotic risk in very low-risk ET patients. 3 Prophylactic measures beyond standard obstetric or surgical protocols are not required, though close monitoring remains prudent.