What is the treatment for thrombocytosis?

Treatment of Thrombocytosis

The treatment of thrombocytosis should be risk-stratified, with cytoreductive therapy indicated for high-risk patients (age >60 years and/or history of thrombosis) and those with platelet counts >1,500 × 10⁹/L, while low-risk patients may be managed with observation or low-dose aspirin. 1

Risk Stratification for Essential Thrombocythemia (ET)

Risk stratification is crucial for determining appropriate treatment:

• Very low-risk: Age ≤60 years, no JAK2 mutation, no prior history of thrombosis
• Low-risk: Age ≤60 years, with JAK2 mutation, no prior history of thrombosis
• High-risk: Age >60 years and/or prior history of thrombosis 1

Treatment Approach Based on Risk Category

Very Low-Risk Patients

• Observation without cytoreductive therapy
• Monitor for new thrombosis, acquired von Willebrand disease (VWD), and/or disease-related major bleeding 1

Low-Risk Patients

• Manage cardiovascular risk factors
• Low-dose aspirin (81-100 mg/day) for vascular symptoms
• Consider observation without aspirin for CALR-mutated ET patients 1
• Initiate cytoreductive therapy if:
  • Symptomatic thrombocytosis develops
  • Progressive leukocytosis occurs
  • Disease-related symptoms progress
  • Vasomotor/microvascular disturbances not responsive to aspirin develop 1

High-Risk Patients

• Cytoreductive therapy is indicated
• Hydroxyurea is the first-line cytoreductive agent at any age (though use should be carefully considered in patients <40 years) 1
• Low-dose aspirin in addition to cytoreductive therapy 1

Specific Indications for Cytoreductive Therapy

Cytoreductive therapy should be initiated in the following scenarios:

1. High-risk patients (age >60 years and/or history of thrombosis)
2. Platelet count >1,500 × 10⁹/L (associated with risk of bleeding due to acquired VWD)
3. Progressive increasing leukocyte and/or platelet count
4. Enlarging spleen
5. Uncontrolled disease-related symptoms
6. Development of thrombotic or hemorrhagic complications 1

Cytoreductive Treatment Options

First-Line Options

• Hydroxyurea: Initial dosage 500 mg twice daily; most commonly used first-line agent 1
• Interferon-α: Preferred in younger patients (<40 years) and women of childbearing age; initial dosage 3 million U subcutaneously 3 times a week 1
• Anagrelide: FDA-approved for treatment of thrombocythemia secondary to myeloproliferative neoplasms 2

Second-Line Options

• For patients resistant or intolerant to first-line therapy with hydroxyurea, consider anagrelide or interferon-α 1
• For elderly patients with treatment compliance issues and life expectancy <10 years, consider 32P 1

Aspirin Therapy Considerations

• Standard low-dose aspirin (81-100 mg/day) is recommended for high-risk patients and those with microvascular symptoms 1, 3
• Twice-daily low-dose aspirin (37.5 mg twice daily) may provide more consistent platelet inhibition than once-daily dosing 4, 3
• Plain aspirin should be preferred over enteric-coated formulations due to potential resistance issues in ET patients 3
• Aspirin should be used with caution in patients with acquired VWD or platelet counts >1,500 × 10⁹/L 1

Special Considerations

• In patients with platelet counts <50 × 10⁹/L who require anticoagulation, consider withholding anticoagulants or using reduced doses with close monitoring 5
• For patients with symptomatic thrombocytosis, treatment options include hydroxyurea, antiaggregants, anagrelide, or apheresis 1
• Patients with ET who develop thrombocytopenia (<50 × 10⁹/L) during treatment should have their cytoreductive therapy dose reduced or temporarily discontinued 5

Monitoring Response

• Evaluate response by normalization of blood counts and resolution of signs/symptoms of disease
• Complete hematologic response includes:
  • Leukocyte count <10 × 10⁹/L
  • Platelet count <450 × 10⁹/L
  • No immature cells in peripheral blood
  • No signs/symptoms of disease with disappearance of palpable splenomegaly 1

Pitfalls and Caveats

• Thrombocytosis (platelet count >1,000 × 10⁹/L) has been associated with an immediate risk of major hemorrhage but paradoxically with a lower risk of thrombosis in ET patients 1
• Leukocytosis at diagnosis is associated with higher risk of thrombosis and major hemorrhage in patients with ET 1
• Multiple cytotoxic agents should be avoided as they significantly increase the risk of developing acute myeloid leukemia/myelodysplastic syndromes 1
• Reactive thrombocytosis should be ruled out before initiating treatment for suspected ET 6