Is aspirin indicated in polycythemia vera?

Aspirin in Polycythemia Vera: Evidence-Based Recommendations

Low-dose aspirin (81-100 mg daily) is strongly indicated for all patients with polycythemia vera to reduce the risk of thrombotic complications, regardless of risk stratification. 1, 2

Rationale for Aspirin Use in Polycythemia Vera

Polycythemia vera (PV) is characterized by a high risk of thrombotic complications, with a pooled prevalence of overall thrombosis of 28.6% in newly diagnosed patients 2. This high thrombotic risk significantly impacts morbidity and mortality.

The evidence supporting aspirin use in PV comes primarily from:

• The ECLAP trial (European Collaboration on Low-dose Aspirin in Polycythemia Vera), which demonstrated that aspirin safely reduced the risk of 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, 3

• The benefit was observed without a significant increase in major bleeding episodes (RR, 1.62; 95% CI, 0.27 to 9.71) 3

Risk Stratification and Treatment Algorithm

Risk Categories:

1. Low-risk PV: Age <60 years and no history of thrombosis
2. High-risk PV: Age ≥60 years or history of thrombosis

Treatment Approach:

For Low-risk Patients:

• Phlebotomy to maintain hematocrit <45%
• Low-dose aspirin (81-100 mg daily) 1, 2

For High-risk Patients:

• Phlebotomy to maintain hematocrit <45%
• Low-dose aspirin (81-100 mg daily)
• Cytoreductive therapy (typically hydroxyurea) 1, 2

Special Considerations

Dosing Frequency

• One-third of aspirin-treated PV patients display less-than-maximal platelet thromboxane inhibition, particularly those with higher platelet counts 4
• Twice-daily aspirin (81-100 mg twice daily) may be considered for patients with inadequate response to once-daily dosing or those at particularly high thrombotic risk 4

Bleeding Risk

• Aspirin should be used with caution in patients with acquired von Willebrand disease or platelet count >1,500 × 10^9/L due to increased bleeding risk 1, 2
• Monitor for bleeding complications, especially with concomitant use of other antithrombotic agents

Hematocrit Target

• Maintain hematocrit <45% in all patients regardless of gender
• The CYTO-PV trial demonstrated that targeting hematocrit <45% significantly reduced the composite primary endpoint of cardiovascular death or major thrombotic events compared to less intensive treatment (HR 3.91; 95% CI, 1.45–10.53; P=0.007) 2

Monitoring Recommendations

1. Regular assessment of complete blood counts
2. Monitoring of serum thromboxane B2 levels may help identify patients with inadequate platelet inhibition who might benefit from twice-daily aspirin dosing 4
3. Evaluation for signs of disease progression
4. Assessment for thrombotic or bleeding complications

Potential Pitfalls

1. Inadequate antiplatelet effect: Higher platelet counts may reduce aspirin efficacy, requiring consideration of twice-daily dosing
2. Enteric-coated preparations: May have lower bioavailability and inadequate platelet inhibition, particularly in heavier patients 2
3. Missing doses: Can significantly reduce protection, especially with once-daily regimens 4
4. Failure to address other cardiovascular risk factors: Aggressive management of hypertension, hyperlipidemia, diabetes, and smoking cessation remains crucial 1

In conclusion, low-dose aspirin is a cornerstone therapy in PV management, with strong evidence supporting its use for thrombosis prevention with an acceptable safety profile. The combination of aspirin with appropriate phlebotomy and risk-adapted cytoreductive therapy provides optimal protection against the thrombotic complications that characterize this disease.