What is the treatment for essential thrombocytosis?

Treatment of Essential Thrombocytosis

Treatment of essential thrombocythemia (ET) is risk-stratified, with high-risk patients (age >60 years, prior thrombosis, or JAK2 mutation) requiring cytoreductive therapy with hydroxyurea plus low-dose aspirin (81-100 mg/day), while low-risk patients may be managed with aspirin alone or observation. 1, 2

Risk Stratification Framework

The cornerstone of ET management is accurate risk stratification to determine appropriate therapy intensity:

Very Low Risk:

• Age ≤60 years, no JAK2 mutation, no prior thrombosis
• Management: Observation without cytoreductive therapy 2

Low Risk:

• Age ≤60 years, JAK2 mutation present, no prior thrombosis
• Management: Low-dose aspirin (81-100 mg/day) for vascular symptoms and cardiovascular risk factor management 2

Intermediate Risk:

• Age >60 years, no prior thrombosis, JAK2 wild-type
• Management: Low-dose aspirin plus consideration of cytoreductive therapy based on additional risk factors 2

High Risk:

• Prior thrombosis at any age OR age >60 years with JAK2 mutation
• Management: Low-dose aspirin (81-100 mg/day) PLUS cytoreductive therapy 1, 2

Primary Treatment Modalities

Low-Dose Aspirin

Aspirin (81-100 mg/day) is recommended for most ET patients to reduce thrombotic risk, particularly those with microvascular symptoms like erythromelalgia or transient ischemic attacks. 1, 3

• In a retrospective study of 300 low-risk patients not taking aspirin, arterial thrombosis occurred at 9.4/1000 patient-years and venous thrombosis at 8.2/1000 patient-years 3
• Aspirin is especially effective in ET patients with myeloproliferative disease, with dramatic improvement reported within days 1
• The combination of aspirin with anagrelide increases bleeding risk, particularly in patients with platelet counts >1,000 × 10⁹/L 4, 5

Cytoreductive Therapy

Hydroxyurea is the first-line cytoreductive agent for high-risk ET patients. 1, 2

• 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
• Cytoreductive therapy is indicated for: age >60 years, prior thrombosis history, platelet count >1,500 × 10⁹/L, or presence of vascular disease 6, 7
• Bone marrow aspirate and biopsy should be performed before initiating cytoreductive therapy to rule out disease progression 2

Alternative Cytoreductive Agents

Anagrelide and interferon-alpha are alternatives when hydroxyurea cannot be tolerated. 4, 6, 7

• Anagrelide starting dose: 0.5 mg to 2.0 mg every 6 hours, with maximum daily dose of 12 mg 4
• Anagrelide is effective in reducing platelet counts but has increased bleeding risk when combined with aspirin 4
• Interferon-alpha is the preferred cytoreductive agent during pregnancy for high-risk patients 1, 7

Critical Treatment Considerations

Extreme Thrombocytosis Management

For platelet counts >1,500 × 10⁹/L, screen for acquired von Willebrand syndrome before initiating aspirin to avoid bleeding complications. 2

• Treatment options for symptomatic thrombocytosis include hydroxyurea, anagrelide, or apheresis 1
• Bleeding risk increases significantly at platelet counts exceeding 1,000 × 10⁹/L, particularly with aspirin therapy 5

Pregnancy Management

All pregnant women with ET should receive aspirin therapy, with interferon-alpha added for high-risk patients or those with recurrent fetal loss. 1

• Live birth rate in ET is approximately 70%, with first trimester fetal loss (~30%) as the major complication 1
• Low molecular weight heparin is indicated for patients with prior venous thrombosis 1
• Hydroxyurea and anagrelide are contraindicated during pregnancy 1

Monitoring and Long-Term Considerations

Regular complete blood counts are essential, with surveillance for disease progression to myelofibrosis (10% at 8.5 years) or acute myeloid leukemia (3% at 8.5 years). 2, 3

• Median overall survival exceeds 35 years in patients diagnosed at age ≤40 years 3
• The 5-year and 10-year survival probabilities are 93% and 84%, respectively, indicating near-normal life expectancy 5

Common Pitfalls to Avoid

Do not use therapeutic phlebotomy in ET (unlike polycythemia vera), as this is not indicated. 2

Avoid delaying cytoreductive therapy in high-risk patients, as this significantly increases thrombotic complications. 2, 3

Do not combine aspirin with anagrelide without careful bleeding risk assessment, particularly in patients with platelet counts >1,000 × 10⁹/L or bleeding history. 4, 5

Monitor for drug interactions when using anagrelide, particularly with CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) which increase anagrelide exposure and cardiovascular risk. 4