Can a patient with thrombocytosis be prescribed aspirin?

Aspirin in Thrombocytosis: Risk-Stratified Approach

Yes, aspirin can be prescribed for patients with thrombocytosis, but the decision depends critically on whether the thrombocytosis is reactive or due to a myeloproliferative neoplasm (MPN), the platelet count level, bleeding risk, and presence of JAK2/CALR mutations. 1, 2

Distinguish the Underlying Cause First

Reactive thrombocytosis (RT) has never been shown to cause thrombosis even at platelet counts >1,000×10⁹/L, and aspirin is not indicated—instead, identify and treat the underlying inflammatory, infectious, or malignant condition causing the elevated platelets. 3

Essential thrombocythemia (ET) and polycythemia vera (PV) are MPNs where aspirin plays a defined role based on risk stratification. 1

Risk-Stratified Aspirin Recommendations for Essential Thrombocythemia

Very Low-Risk and Low-Risk ET

• Observation alone is appropriate for very low-risk patients (age <60 years, no thrombosis history, platelet count <1,000×10⁹/L). 1
• Withhold aspirin in low-risk patients with platelet counts >1,000×10⁹/L due to acquired von Willebrand disease risk causing paradoxical bleeding. 1, 4
• Withhold aspirin in patients with CALR mutations, as retrospective data show no thrombosis benefit but increased bleeding risk. 1
• Consider aspirin 81-100 mg daily for low-risk patients with JAK2 mutations or cardiovascular risk factors, as retrospective analysis suggests benefit in this subgroup. 1

Intermediate-Risk and High-Risk ET

• Aspirin 81-100 mg daily is recommended for intermediate-risk patients (age 40-60 years with JAK2 mutation, or cardiovascular risk factors). 1
• Cytoreductive therapy (hydroxyurea or anagrelide) plus aspirin 81-100 mg daily is the standard for high-risk patients (age ≥60 years or prior thrombosis). 1

Symptomatic ET (Vasomotor Disturbances)

• Aspirin 81-100 mg daily is indicated for erythromelalgia, transient ischemic attacks, visual disturbances, or acrocyanosis regardless of risk category, as these symptoms are cyclooxygenase-mediated and aspirin-responsive. 4, 5

Polycythemia Vera Recommendations

All PV patients require aspirin 81-100 mg daily plus phlebotomy to maintain hematocrit <45%, regardless of risk category, based on the ECLAP study showing thrombosis prevention benefit. 1, 2

Critical Platelet Count Thresholds

• Platelet counts <1,000×10⁹/L: Aspirin is safe when indicated. 4, 5
• Platelet counts 1,000-1,500×10⁹/L: Use aspirin with extreme caution; acquired von Willebrand syndrome may be present, creating paradoxical bleeding risk. 1, 4
• Platelet counts >1,500×10⁹/L: Aspirin is contraindicated due to high bleeding risk from acquired von Willebrand factor deficiency; cytoreductive therapy to lower platelet count is mandatory before considering aspirin. 4, 6, 5

Optimal Aspirin Dosing and Formulation

Use plain (non-enteric-coated) aspirin 81-100 mg daily, as enteric-coated formulations show poor responsiveness in some ET patients due to inadequate bioavailability. 7, 8

Consider twice-daily aspirin (100 mg every 12 hours) in carefully selected ET patients with persistent vasomotor symptoms, as once-daily dosing fails to maintain 24-hour platelet inhibition due to high platelet turnover in ET. 1, 8 This regimen has proven safe in small studies and addresses the unique pathophysiology of ET where immature platelets with non-acetylated cyclooxygenase-1 continuously enter circulation. 8

Higher doses (>100 mg daily) provide no additional antithrombotic benefit but significantly increase gastrointestinal bleeding risk. 1, 7

Monitoring and Safety

• Screen for acquired von Willebrand disease before initiating aspirin in patients with platelet counts >1,000×10⁹/L by measuring von Willebrand factor antigen and ristocetin cofactor activity. 1, 4
• Monitor for bleeding symptoms including petechiae, epistaxis, gastrointestinal bleeding, or easy bruising, particularly in the first 3 months of therapy. 9
• Assess platelet count every 3-6 months and adjust cytoreductive therapy to maintain platelets <1,000×10⁹/L in high-risk patients. 1

Common Pitfalls to Avoid

Do not prescribe aspirin for reactive thrombocytosis—this exposes patients to bleeding risk without benefit, as RT does not cause thrombosis. 3

Do not use aspirin in ET patients with prior major bleeding or those with platelet counts >1,500×10⁹/L without first reducing platelet count with cytoreductive therapy. 4, 6

Do not assume all thrombocytosis patients need aspirin—CALR-mutated ET patients may experience harm rather than benefit. 1

Do not use enteric-coated aspirin as the primary formulation in ET, as pharmacological resistance is more common with this preparation. 8