What is the role of aspirin (acetylsalicylic acid) in patients with polycythemia vera, particularly those at high risk of thrombotic events?

Aspirin Therapy in Polycythemia Vera

Low-dose aspirin (100 mg daily) should be given to all patients with polycythemia vera who have no contraindications, as it significantly reduces thrombotic complications without substantially increasing bleeding risk. 1

Evidence Base and Efficacy

The landmark ECLAP (European Collaboration on Low-dose Aspirin in Polycythemia Vera) trial definitively established aspirin's role in PV by demonstrating a 60% 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). 2, 1 Critically, this benefit was achieved without a significant increase in major bleeding compared to placebo. 2, 1

This contrasts sharply with earlier failed attempts using high-dose aspirin (900 mg/d) combined with dipyridamole, which showed no thrombosis benefit but increased gastrointestinal bleeding. 2 The dose matters enormously—low-dose aspirin (40-100 mg/d) provides effective platelet inhibition without the bleeding complications seen with higher doses. 2

Recommended Dosing and Administration

The standard dose is 100 mg once daily, which represents the lowest effective dose demonstrated in the ECLAP trial specifically for PV. 2, 1 This dose is listed in the American College of Chest Physicians guidelines as the minimum effective dose for polycythemia vera. 2

• Regular (non-enteric-coated) aspirin is preferred as it provides more reliable platelet inhibition, with peak plasma levels at 30-40 minutes and platelet inhibition evident within 1 hour. 1
• The 100 mg daily dose effectively suppresses enhanced thromboxane A2 biosynthesis characteristic of PV. 3, 4

Integration with Comprehensive PV Management

Aspirin is a cornerstone therapy but must be combined with other interventions:

For ALL PV Patients (Low and High Risk):

• Phlebotomy to maintain hematocrit <45% is mandatory, as the CYTO-PV study demonstrated that this target resulted in significantly lower cardiovascular death and major thrombotic events (2.7% vs 9.8%; P=0.007) compared to hematocrit 45-50%. 2, 1
• Low-dose aspirin 100 mg daily unless contraindicated. 1
• Aggressive cardiovascular risk factor management including hypertension, diabetes, hyperlipidemia control, and smoking cessation. 1, 5

For High-Risk Patients (Age >60 years OR prior thrombosis):

• Add cytoreductive therapy (hydroxyurea as first-line or interferon-alpha for younger/pregnant patients) in addition to aspirin and phlebotomy. 2, 1

Absolute Contraindications to Aspirin

Aspirin must be withheld in the following situations:

• 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, as aspirin significantly increases bleeding risk in this subset. 2, 1, 3

Critical Pitfall to Avoid:

Patients with platelet counts >1,000 × 10⁹/L have increased hemorrhagic events that are enhanced by aspirin therapy. 3 In these patients, cytoreduction to lower platelet counts should precede or accompany aspirin initiation, and aspirin should be used with extreme caution if acquired von Willebrand disease is present. 2, 3

Duration and Monitoring

• Continue aspirin indefinitely unless contraindications develop. 1
• Monitor for new thrombosis, acquired von Willebrand disease, and disease-related major bleeding every 3-6 months. 2
• Assess symptom burden using validated tools (MPN-SAF TSS) to evaluate treatment response. 2

Special Considerations

While the ECLAP trial established aspirin's efficacy in PV, no randomized trials have been conducted in essential thrombocythemia (ET). 6, 7 The use of aspirin in ET is extrapolated from PV data, and recent retrospective analyses suggest variable benefit depending on mutation status (JAK2 vs CALR). 2 However, for PV specifically, the evidence is robust and unequivocal.

The earlier concern about leukemogenic risk from cytoreductive agents does not apply to aspirin monotherapy, which has no association with leukemic transformation. 2