What is the management of thrombocytosis?

Management of Thrombocytosis

The management of thrombocytosis should first distinguish between reactive thrombocytosis and essential thrombocythemia (ET), with treatment focused on underlying causes for reactive cases and risk-stratified therapy for ET patients to prevent thrombotic complications. 1

Diagnostic Approach

1. Determine if thrombocytosis is reactive or primary:

   • Reactive thrombocytosis: Secondary to inflammation, iron deficiency, recent surgery, or underlying neoplasm
   • Primary thrombocytosis: Essential thrombocythemia (ET) or other myeloproliferative neoplasms

2. Key diagnostic tests:

   • Complete blood count with peripheral smear
   • Iron studies
   • Inflammatory markers (CRP, ESR)
   • JAK2, CALR, and MPL mutation testing
   • Bone marrow examination if primary thrombocytosis suspected

Management of Reactive Thrombocytosis

• Identify and treat the underlying cause (infection, inflammation, iron deficiency, etc.)
• No specific treatment for the elevated platelet count is typically needed
• Even with very high platelet counts (>1000 × 10⁹/L), reactive thrombocytosis rarely causes thrombosis 2
• Antiplatelet therapy is generally not indicated in reactive thrombocytosis

Management of Essential Thrombocythemia

Risk Stratification

ET patients should be stratified into risk categories to guide treatment 1:

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

Treatment Recommendations

1. Antiplatelet Therapy:

   • Low-dose aspirin (40-325 mg) once daily for all patients with platelet counts <1,500 × 10⁹/L 1, 3
   • Twice daily low-dose aspirin for low-risk disease 1
   • Avoid aspirin if platelet count >1,500 × 10⁹/L due to acquired von Willebrand factor defects

2. Cytoreductive Therapy:

   • High-risk patients: Cytoreductive therapy is indicated 1, 3
   • Intermediate-risk patients: Cytoreductive therapy is optional 1
   • Low/very low-risk patients: Observation or antiplatelet therapy alone

3. First-line cytoreductive options:

   • Hydroxyurea
   • Pegylated interferon-α

4. Second-line options:

   • Anagrelide (effective for long-term control of thrombocytosis) 4
   • Busulfan 1

Special Considerations

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

• Increased risk of bleeding due to acquired von Willebrand syndrome
• Avoid aspirin until platelet count is reduced 3
• Initiate cytoreductive therapy

Pregnancy

• Low-risk pregnant women: Observation with or without low-dose aspirin
• High-risk pregnant women: Interferon-α is the preferred cytoreductive agent 3
• Regular platelet count monitoring throughout pregnancy 5

Perioperative Management

For invasive procedures, consider the following platelet thresholds 5:

• Central venous catheter insertion: >20 × 10⁹/L
• Lumbar puncture: >40-50 × 10⁹/L
• Epidural anesthesia: >80 × 10⁹/L
• Major surgery: >50 × 10⁹/L
• Neurosurgery: >100 × 10⁹/L

Monitoring and Follow-up

• Regular monitoring of platelet counts
• Assess for thrombotic or hemorrhagic complications
• Monitor for disease transformation (myelofibrosis, acute leukemia)
• Cardiac monitoring for patients on anagrelide 4

Pitfalls and Caveats

• Do not assume all thrombocytosis requires treatment. Reactive thrombocytosis rarely causes complications.
• Avoid aspirin in patients with very high platelet counts (>1,500 × 10⁹/L) due to risk of bleeding from acquired von Willebrand syndrome.
• Consider cardiac function before initiating anagrelide, as it may cause cardiac disorders in approximately 8% of patients 4.
• Recognize that cytoreductive therapy carries a small risk of leukemic transformation. The leukemic transformation rate at 10 years is <1% but might be higher in JAK2-mutated patients 1.