What is the treatment for thrombocytosis?

Treatment of Thrombocytosis

The treatment of thrombocytosis should be based on whether it is primary (essential thrombocythemia) or secondary (reactive), with risk stratification guiding therapeutic decisions in primary cases.

Differentiating Primary vs Secondary Thrombocytosis

• Secondary (reactive) thrombocytosis is much more common, especially in children, and is caused by various conditions including infections, iron deficiency, bleeding, hemolytic anemias, collagen vascular diseases, malignancies, drugs, and splenectomy 1
• Primary thrombocytosis (essential thrombocythemia) is a clonal myeloproliferative neoplasm characterized by sustained thrombocytosis and is relatively rare, especially in childhood 2, 1
• Diagnosis of primary thrombocytosis requires exclusion of other myeloid neoplasms including prefibrotic myelofibrosis, polycythemia vera, chronic myeloid leukemia, and myelodysplastic syndromes 3

Treatment of Secondary Thrombocytosis

• Secondary thrombocytosis should be managed by treating the underlying cause alone 1
• Administration of platelet aggregation inhibitors such as aspirin is generally not warranted in reactive thrombocytosis 1
• Even with platelet counts >1000 × 10^9/L, thrombosis prophylaxis is typically not required in secondary thrombocytosis unless additional prothrombotic risk factors are present 4

Treatment of Primary Thrombocytosis (Essential Thrombocythemia)

Risk Stratification

Essential thrombocythemia patients should be stratified into risk categories to guide treatment 5, 3:

• Very low risk: Age ≤60 years, no thrombosis history, JAK2 wild-type 3
• Low risk: Age <60 years, no thrombosis history, JAK2 mutation present 3
• Intermediate risk: Age >60 years, no thrombosis history, JAK2 mutation present 3
• High risk: Any age with prior thrombosis or age >60 years with JAK2 mutation 5, 3

Treatment Recommendations

1. Very low and low-risk patients:

   • Once-daily low-dose aspirin (40-325 mg) for all patients; twice daily for low-risk disease 5, 3
   • Observation without cytoreductive therapy if platelet count <1,500 × 10^9/L 5

2. Intermediate-risk patients:

   • Low-dose aspirin if platelet count <1,500 × 10^9/L 5
   • Cytoreductive therapy is optional 3
   • Treatment of cardiovascular risk factors 5

3. High-risk patients:

   • Cytoreductive therapy is recommended 5, 3
   • First-line cytoreductive drugs: hydroxyurea or pegylated interferon-α 3
   • Second-line: busulfan 3
   • Low-dose aspirin if platelet count <1,500 × 10^9/L 5

4. Extreme thrombocytosis (>1,500 × 10^9/L):

   • Cytoreductive therapy should be considered regardless of other risk factors 5
   • Avoid aspirin until platelet count is reduced to <1,500 × 10^9/L due to increased bleeding risk 5

Special Populations

Pregnant Women

• Low-risk pregnant women can be managed with low-dose aspirin if platelet count <1,500 × 10^9/L 5
• High-risk pregnant women who need cytoreductive therapy should receive interferon-α, as it is considered safer during pregnancy 5

Polycythemia Vera with Thrombocytosis

• For patients with polycythemia vera and thrombocytosis, treatment includes:
  • Phlebotomy to maintain hematocrit <42% for women and <45% for men 5
  • High-risk patients should receive hydroxyurea or interferon-α in addition to phlebotomy 5
  • Low-dose aspirin if platelet count <1,500 × 10^9/L 5

Monitoring and Complications

• The main goal of therapy in essential thrombocythemia is to prevent thrombosis 3
• Patients should be monitored for potential complications including thrombosis, hemorrhage, and disease transformation into myelofibrosis or acute myeloid leukemia 3
• Leukemic transformation rate at 10 years is <1% but might be higher in JAK2-mutated patients with extreme thrombocytosis 3

Common Pitfalls and Caveats

• Avoid unnecessary treatment of reactive thrombocytosis with antiplatelet agents 1
• Do not overlook the possibility of primary thrombocytosis in patients with persistent elevated platelet counts without an obvious cause 2
• Remember that secondary thrombocytosis in children is common and benign, while primary thrombocytosis is extremely rare 1, 4
• In polycythemia vera patients, platelet counts have not been definitively linked to increased thrombosis risk, but age and history of thrombosis are important risk factors 5