What is the treatment for thrombocytosis?

Treatment for Thrombocytosis

The treatment for thrombocytosis depends on the underlying cause, risk stratification, and whether it is reactive or essential thrombocythemia (ET), with low-dose aspirin plus risk-adapted cytoreductive therapy being the cornerstone of management for ET. 1

Risk Stratification for Essential Thrombocythemia

Risk stratification is critical for determining appropriate treatment:

Risk Categories:

• Very Low Risk: Age ≤60 years, no JAK2 mutation, no prior thrombosis
• Low Risk: Age ≤60 years, JAK2 mutation present, no prior thrombosis
• Intermediate Risk: Age >60 years, JAK2 mutation present, no prior thrombosis
• High Risk: Any age with prior thrombosis OR age >60 years with JAK2 mutation 1, 2

Treatment Algorithm

1. For Very Low-Risk ET:

• Observation alone is appropriate
• Aspirin (81-100 mg/day) only if microvascular symptoms are present 1

2. For Low-Risk ET:

• Aspirin (81-100 mg/day) for vascular symptoms
• Consider twice-daily aspirin regimen (37.5-50 mg twice daily) for better platelet inhibition 3, 4
• Monitor for: thrombosis, bleeding, disease progression 1

3. For Intermediate-Risk ET:

• Aspirin (81-100 mg/day)
• Consider cytoreductive therapy (optional) 1, 2

4. For High-Risk ET:

• Cytoreductive therapy + aspirin (81-100 mg/day) 1
• First-line cytoreductive options:
  • Hydroxyurea (most commonly used)
  • Interferon alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b (preferred for younger patients and pregnant patients) 1
• Second-line options:
  • Anagrelide (FDA approved specifically for thrombocythemia secondary to myeloproliferative disorders) 5
  • Switch to interferon if intolerant to hydroxyurea 1

5. Special Considerations:

For Extreme Thrombocytosis (>1,500 × 10^9/L):

• Higher bleeding risk due to acquired von Willebrand disease
• Initiate cytoreductive therapy regardless of risk category
• Use aspirin with caution or withhold until platelet count is reduced 1, 6

For Reactive Thrombocytosis:

• Treat the underlying cause (infection, inflammation, iron deficiency, etc.)
• Aspirin is generally not indicated as thrombotic risk is not increased 7

Monitoring Response

• Evaluate response by normalization of blood counts and resolution of symptoms
• Monitor for:
  • New thrombosis
  • Acquired von Willebrand disease
  • Disease-related major bleeding
  • Progressive splenomegaly
  • Disease transformation to myelofibrosis or acute leukemia 1

Treatment Modifications

• Change therapy if intolerance develops (see below)
• Withdraw aspirin in case of major bleeding or intolerance 1

Criteria for Hydroxyurea Intolerance/Resistance:

• Failure to reduce platelet count below 600 × 10^9/L after 3 months at maximum tolerated dose
• Development of cytopenia at lowest effective dose
• Failure to reduce splenomegaly by 50%
• Persistent disease-related symptoms 1

Important Caveats

• The evidence supporting aspirin in ET is extrapolated from studies in polycythemia vera, and its benefit in all ET patients remains uncertain 7, 3
• Twice-daily aspirin dosing may provide more consistent platelet inhibition than once-daily dosing in ET patients 4
• Patients with CALR mutations may have less benefit from aspirin prophylaxis 1, 3
• Cytoreductive therapy should be used cautiously in younger patients due to potential leukemogenic effects with long-term use 1
• Multiple cytotoxic agents should be avoided due to increased risk of leukemic transformation 1

By following this risk-adapted approach, thrombotic and hemorrhagic complications can be minimized while reducing the risk of disease progression and treatment-related adverse events.