What is the initial approach to treating thrombocytosis?

Initial Approach to Treating Thrombocytosis

The initial approach to thrombocytosis requires first distinguishing between primary (essential thrombocythemia) and secondary causes through clinical assessment and targeted testing, as treatment differs fundamentally between these two categories. 1, 2

Step 1: Determine if Thrombocytosis is Primary or Secondary

Clinical Features Suggesting Secondary Thrombocytosis

• Active malignancy (solid tumors or hematological conditions) 2, 3
• Chronic inflammatory disease (rheumatoid arthritis, inflammatory bowel disease) 2
• Recent tissue injury or surgery (accounts for 32.2% of secondary cases) 1
• Active infection (17.1% of secondary cases) 1
• Iron deficiency anemia (11.1% of secondary cases) 1, 2
• Prior splenectomy 2

Laboratory Features Distinguishing Primary from Secondary

Essential thrombocythemia is associated with:

• Higher hemoglobin levels 2
• Higher mean corpuscular volume (MCV) 2
• Higher red cell distribution width (RDW) 2
• Higher mean platelet volume (MPV) 2
• Platelet counts typically >600 × 10⁹/L (median significantly higher than secondary) 1

Secondary thrombocytosis is associated with:

• Higher white blood cell and neutrophil counts 2
• Evidence of underlying inflammatory or infectious process 3

Step 2: Molecular Testing Strategy

When to Order Molecular Testing

Order JAK2, CALR, and MPL mutation testing when:

• No clear secondary cause is identified after clinical assessment 4, 2
• Platelet count persistently >450 × 10⁹/L without obvious reactive etiology 4
• History of arterial thrombosis (predictive of essential thrombocythemia) 2

Avoid molecular testing when:

• Clear secondary causes are present (active malignancy, chronic inflammation, iron deficiency, recent surgery) 2
• This approach reduces unnecessary costly testing, as 92.1% of positive molecular results are JAK2, CALR, or MPL mutations 2

Bone Marrow Examination

• Required for formal diagnosis of essential thrombocythemia to exclude prefibrotic myelofibrosis, polycythemia vera, and myelodysplastic syndromes 4
• Shows increased mature-appearing megakaryocytes in loose clusters 4

Step 3: Treatment Based on Diagnosis

For Secondary Thrombocytosis

Treat the underlying cause:

• Address active infection 1
• Manage chronic inflammatory disease 1
• Correct iron deficiency 1
• No cytoreductive therapy needed unless platelet count >1,500 × 10⁹/L with bleeding symptoms 5

For Essential Thrombocythemia: Risk Stratification

Very Low Risk (age ≤60 years, no thrombosis history, JAK2 wild-type):

• Once-daily low-dose aspirin (40-325 mg) 5, 4
• Observation without cytoreductive therapy 5

Low Risk (age ≤60 years, no thrombosis history, JAK2 mutation present):

• Once-daily low-dose aspirin 4
• Consider twice-daily aspirin for microcirculatory symptoms 4

Intermediate Risk (age >60 years, no thrombosis history, JAK2 mutation present):

• Low-dose aspirin 4
• Optional cytoreductive therapy with hydroxyurea or pegylated interferon-α 4

High Risk (age >60 years with JAK2 mutation OR any age with thrombosis history):

• Low-dose aspirin 4
• Mandatory cytoreductive therapy with first-line hydroxyurea or pegylated interferon-α 5, 4
• Second-line options include busulfan or anagrelide 5, 4

Step 4: Special Considerations

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

• Avoid aspirin due to acquired von Willebrand syndrome and major hemorrhage risk 5
• Initiate cytoreductive therapy regardless of risk category 5
• Consider hydroxyurea, anagrelide, or interferon-α 5

Pregnancy

• Interferon-α is the only cytoreductive agent safe in pregnancy for high-risk patients 5, 4
• Low-dose aspirin can be used if platelet count <1,500 × 10⁹/L 5

Thrombosis Risk

• Thrombosis incidence is significantly higher in primary versus secondary thrombocytosis 1
• JAK2V617F mutation specifically increases thrombotic risk 4
• History of arterial thrombosis strongly predicts essential thrombocythemia 2