What is the treatment for a patient with essential thrombocytosis?

Treatment of Essential Thrombocythemia

Treatment for essential thrombocythemia is determined by thrombotic risk stratification, with high-risk patients requiring cytoreductive therapy plus 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, no JAK2 mutation
• 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 history of thrombosis at any age OR age >60 years with JAK2 mutation 1

Treatment Algorithm by Risk Category

High-Risk Patients

High-risk patients require cytoreductive therapy combined with aspirin. 1

First-line cytoreductive therapy:

• Hydroxyurea is the preferred first-line agent, with dosing adjusted to maintain platelet count <400-450 × 10⁹/L 1, 2, 3
• Pegylated interferon-α is the preferred alternative, particularly for younger patients or those of childbearing age 1, 2, 3

Second-line options:

• Anagrelide can be used if hydroxyurea or interferon are not tolerated 1, 4
• Busulfan represents a third-line option 3

Aspirin therapy:

• Low-dose aspirin (81-100 mg daily) should be added for vascular symptom prevention 1, 2
• Caution: Aspirin should be used carefully in patients with acquired von Willebrand disease, particularly with extreme thrombocytosis (>1,000 × 10⁹/L) 1, 2

Low-Risk Patients

Low-risk patients can be managed with low-dose aspirin alone (81-100 mg daily). 2, 5

• Observation without aspirin is an alternative for very low-risk patients without cardiovascular risk factors 6
• In a retrospective study of 300 low-risk patients not taking aspirin, arterial thrombosis risk was 9.4/1000 patient-years and venous thrombosis risk was 8.2/1000 patient-years 5

Intermediate-Risk Patients

Intermediate-risk patients should receive aspirin, with cytoreductive therapy optional based on additional risk factors. 1

• Cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, smoking) should be aggressively managed 2, 5
• Consider cytoreductive therapy if cardiovascular risk factors are present or platelet count exceeds 1,500 × 10⁹/L 6

Special Clinical Situations

Extreme Thrombocytosis (>1,500 × 10⁹/L)

• Screen for acquired von Willebrand disease before initiating aspirin 2
• Consider cytoreductive therapy due to increased bleeding risk 7, 6
• Platelet apheresis may be used for acute symptomatic management 1, 7

Pregnancy

• Interferon-α (alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b) is the only cytoreductive agent safe for use during pregnancy 1, 7
• Low-dose aspirin can be continued if platelet count <1,500 × 10⁹/L 6
• Avoid estrogen-containing contraceptives; prefer non-hormonal or progesterone-based alternatives 2

Symptomatic Thrombocytosis

For patients with vasomotor symptoms (headaches, erythromelalgia, chest pain) not responsive to aspirin 1:

• Initiate or escalate cytoreductive therapy
• Hydroxyurea remains first-line 1, 7
• Anagrelide or apheresis are alternatives for acute management 1, 7

Monitoring Strategy

Complete blood count monitoring:

• Every 2-4 weeks initially until stable 2, 8
• Every 4-12 weeks once stable 1, 2

Annual bone marrow evaluation should be performed if disease progression is suspected (symptomatic splenomegaly, progressive leukocytosis, new cytopenias) 1, 2

Indications for Changing Cytoreductive Therapy

Consider switching agents if any of the following occur 1:

• Intolerance or resistance to current therapy
• New thrombotic event despite treatment
• Acquired von Willebrand disease with major bleeding
• Symptomatic or progressive splenomegaly
• Progressive leukocytosis
• Vasomotor symptoms not responsive to aspirin

Evidence Supporting Treatment Efficacy

A randomized trial of 114 high-risk patients demonstrated that hydroxyurea significantly reduced thrombotic events compared to no cytoreductive therapy (3.6% vs 24%; P <.01). 5

The ECLAP study in polycythemia vera established that low-dose aspirin resulted in a 60% reduction in combined cardiovascular events (P=.03) without significantly increasing major bleeding risk 1. While this study was in PV, the principles are extrapolated to ET management.

Common Pitfalls

• Do not use platelet count alone as a treatment trigger or goal - thrombotic risk does not correlate with platelet elevation, and extreme thrombocytosis (>1,500 × 10⁹/L) actually increases bleeding risk more than thrombotic risk 9
• Avoid aspirin in patients with extreme thrombocytosis without first screening for acquired von Willebrand disease 1, 2
• Do not use hydroxyurea in pregnant patients - interferon-α is the only safe cytoreductive option 1, 7