Aspirin in Polycythemia Vera: Indications and Dosing
Low-dose aspirin (100 mg daily) is indicated for all patients with polycythemia vera who have no contraindications, as it significantly reduces the risk of both arterial and venous thrombotic complications without substantially increasing bleeding risk. 1
Evidence Base for Aspirin in Polycythemia Vera
The recommendation for aspirin in PV is supported by the landmark ECLAP (European Collaboration on Low-dose Aspirin in Polycythemia Vera) trial, a large double-blind, placebo-controlled randomized study that demonstrated:
- Significant reduction in the combined endpoint of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (RR 0.40; 95% CI 0.18-0.91; P=0.03) 1
- Trend toward reduction in cardiovascular death, nonfatal MI, and nonfatal stroke (RR 0.41; 95% CI 0.15-1.15; P=0.09) 1
- No significant increase in major bleeding compared to placebo 1
This represents Level I, Grade A evidence specifically for polycythemia vera. 1
Recommended Dosing Regimen
The standard dose is 100 mg once daily, which is the lowest effective dose demonstrated in the ECLAP trial for PV. 1
Dosing Considerations:
- Standard formulation preferred: Regular (non-enteric-coated) aspirin provides more reliable platelet inhibition, with peak plasma levels at 30-40 minutes and platelet inhibition evident within 1 hour 1
- Enteric-coated formulations: Have lower bioavailability (may be inadequate at low doses, particularly in heavier patients) and take 3-4 hours to reach peak levels 1
- If rapid effect needed with enteric-coated tablets: Chew rather than swallow intact 1
Emerging Evidence on Dosing Frequency:
Recent pharmacodynamic studies reveal that one-third of PV patients on once-daily aspirin display less-than-maximal platelet thromboxane inhibition, particularly those with higher platelet counts. 2 This reflects accelerated platelet turnover in myeloproliferative neoplasms. 2, 3
- Twice-daily dosing (100 mg BID) may be considered for patients at particularly high thrombotic risk or those with inadequate platelet inhibition on once-daily dosing 2, 3
- Serum thromboxane B2 measurement can guide precision dosing in selected cases 2
Clinical Integration with Other Therapies
Aspirin is a cornerstone of PV therapy alongside phlebotomy to maintain hematocrit <45%. 1
Risk-Stratified Approach:
- All PV patients (low and high risk): Phlebotomy to maintain hematocrit <45% + low-dose aspirin 100 mg daily 1
- High-risk patients (age >60 years or prior thrombosis): Add cytoreductive therapy (hydroxyurea or interferon-alpha) 1
Contraindications and Precautions
Aspirin should be withheld in patients with:
- History of aspirin allergy or hypersensitivity 1
- Active bleeding or high bleeding risk 1
- Acquired von Willebrand syndrome (particularly with extreme thrombocytosis >1,500 × 10⁹/L) 1
Common Pitfall to Avoid:
Do not use higher doses (>100 mg) for chronic prevention in PV, as this increases gastrointestinal bleeding risk without providing additional antithrombotic benefit. 1 The PVSG trial using high-dose aspirin (900 mg/d) plus dipyridamole showed increased gastrointestinal bleeding without thrombotic benefit. 1
Comparison with Other Myeloproliferative Neoplasms
The evidence for aspirin is strongest in polycythemia vera (Level I evidence from ECLAP). 1
- Essential thrombocythemia: Aspirin use is common but lacks randomized trial evidence; benefits may be limited to specific subgroups (older patients, those with microcirculatory symptoms) 4, 5
- Primary myelofibrosis: Lower thrombotic risk (9.5% prevalence); aspirin use not clearly established 1
Monitoring and Long-Term Management
- Cardiovascular risk factor modification is essential: aggressive management of hypertension, diabetes, hyperlipidemia, and smoking cessation 1
- Continue aspirin indefinitely unless contraindications develop 1
- Consider serum thromboxane B2 testing in patients with recurrent thrombosis despite aspirin therapy to assess adequacy of platelet inhibition 2