Should a patient with thrombocytosis be on Aspirin (Acetylsalicylic Acid)?

Should a Patient with Thrombocytosis Be on Aspirin?

The answer depends critically on whether the thrombocytosis is reactive or due to essential thrombocythemia (ET), and if ET, on the patient's risk stratification and JAK2 mutation status. For reactive thrombocytosis, aspirin is not indicated regardless of platelet count, while for ET, aspirin (81-100 mg daily) is recommended for low-risk patients with JAK2 mutation or cardiovascular risk factors, and for all patients with microvascular symptoms 1, 2.

Distinguish Reactive Thrombocytosis from Essential Thrombocythemia

First, determine if the thrombocytosis is reactive or clonal:

• Reactive thrombocytosis (RT) has never been shown to cause thrombosis or bleeding, even at platelet counts >1,000 × 10⁹/L 3
• RT requires identification and treatment of the underlying condition (infection, inflammation, iron deficiency, malignancy, post-splenectomy) rather than aspirin 3
• ET requires formal diagnostic workup including JAK2/CALR/MPL mutation testing and bone marrow biopsy 2
• The presence of JAK2 V617F mutation increases thrombotic risk and influences treatment decisions 2

Risk Stratification for Essential Thrombocythemia

If ET is confirmed, use the revised IPSET-Thrombosis score to stratify risk:

Very Low-Risk ET (Age ≤60 years, no JAK2 mutation, no prior thrombosis)

• Observation without aspirin is appropriate 1
• Monitor for new thrombosis, acquired von Willebrand disease, or disease-related bleeding 1
• Manage cardiovascular risk factors 1

Low-Risk ET (Age ≤60 years, with JAK2 mutation, no prior thrombosis)

• Aspirin 81-100 mg daily is recommended 1, 2
• JAK2 mutation increases thrombotic risk even in younger patients without prior events 1
• Recent retrospective data suggest low-dose aspirin may not benefit CALR-mutated ET patients, but current evidence is insufficient to withhold aspirin from this group 1

High-Risk ET (Age >60 years and/or prior thrombosis)

• Aspirin 81-100 mg daily PLUS cytoreductive therapy (hydroxyurea as first-line) 1, 2
• Target platelet count <400 × 10⁹/L 2
• Advanced age and prior thrombosis are the most consistent risk factors for future thrombotic events 1

Special Considerations for Aspirin Use in ET

Microvascular Symptoms

• Aspirin is the treatment of choice for microvascular occlusive symptoms (erythromelalgia, transient neurologic symptoms, headaches, chest pain) regardless of platelet count in the typical ET range 1, 2, 4
• These symptoms are highly sensitive to aspirin therapy 4

Extreme Thrombocytosis (Platelets >1,000 × 10⁹/L)

• Rule out acquired von Willebrand syndrome (AvWS) with ristocetin cofactor and multimer analysis before starting aspirin 1
• Extreme thrombocytosis is associated with bleeding risk, not thrombosis 1
• Aspirin should be used with extreme caution or avoided if AvWS is present 1
• Bleeding risk with aspirin increases significantly at platelet counts >1,000 × 10⁹/L 5

Dosing Considerations

• Use plain aspirin 81-100 mg daily, not enteric-coated formulations 6
• ET patients may be poor responders to enteric-coated aspirin due to variable absorption and high platelet turnover 6
• Plain aspirin provides more reliable platelet inhibition in all ET patients 6
• Consider twice-daily dosing in patients with persistently elevated platelet counts due to increased platelet turnover producing non-inhibited reticulated platelets 6, 4
• Higher doses (500 mg/day) increase bleeding risk without additional benefit 5

Monitoring and Safety

Bleeding Risk Assessment

• Obtain careful bleeding history before starting aspirin 1, 5
• Aspirin is contraindicated in patients with active bleeding or bleeding history 4
• Monitor for petechiae, ecchymosis, epistaxis, or gastrointestinal bleeding 7
• The absolute bleeding risk with aspirin ranges from 1-2 major events per 1,000 patient-years 7

Platelet Count Monitoring

• Regular complete blood count monitoring is essential to track platelet trends and assess for progression 2
• Serum thromboxane B2 levels correlate with reticulated platelet count and total platelet count at 24 hours after aspirin 6
• ET patients with normalized platelet counts on cytoreductive therapy may not require twice-daily aspirin 6

Common Pitfalls to Avoid

• Do not prescribe aspirin for reactive thrombocytosis - it provides no benefit and adds bleeding risk 3
• Do not use enteric-coated aspirin in ET patients - plain aspirin provides superior and more consistent platelet inhibition 6
• Do not use aspirin doses >100 mg daily - higher doses increase bleeding without additional antithrombotic benefit 7, 5
• Do not start aspirin in extreme thrombocytosis without first excluding AvWS - this combination dramatically increases bleeding risk 1
• Do not withhold aspirin from low-risk JAK2-mutated ET patients - they benefit from thromboprophylaxis despite younger age 1

Evidence Quality Note

The recommendation for aspirin in ET is based primarily on observational data and expert consensus (evidence level IIb, grade B) 3. The widely cited ECLAP study demonstrating aspirin benefit was conducted in polycythemia vera, not ET, and extrapolation between these conditions may be problematic 3. However, aspirin effectively reduces platelet-leukocyte conjugates and platelet activation in ET patients 8, and retrospective data show reduced thrombotic incidence with aspirin therapy 5.