Is there a role for aspirin (acetylsalicylic acid) in preventing thrombotic events in patients with hemoconcentration and elevated hemoglobin levels due to testosterone use?

Aspirin for Hemoconcentration with Elevated Hemoglobin on Testosterone Use

Low-dose aspirin (81-100 mg daily) may be beneficial for patients with hemoconcentration and elevated hemoglobin due to testosterone use who have additional cardiovascular risk factors or evidence of myeloproliferative disorders, but is not routinely recommended for all patients with testosterone-induced erythrocytosis. 1

Pathophysiology and Risk Assessment

• Testosterone therapy can lead to hemoconcentration with elevated hemoglobin levels, increasing blood viscosity and potentially raising thrombotic risk 1
• The primary management of testosterone-induced erythrocytosis should focus on maintaining hematocrit below 45% through phlebotomy rather than relying solely on antiplatelet therapy 1
• High platelet reactivity in patients with elevated hematocrit can increase thrombotic risk 2-4 fold, which may be partially mitigated by aspirin therapy 1

Evidence-Based Recommendations for Specific Scenarios

For Patients with Myeloproliferative Features:

• If testosterone-induced erythrocytosis resembles polycythemia vera (PV) features, low-dose aspirin (81-100 mg daily) plus phlebotomy to maintain hematocrit <45% is recommended 1
• For patients with both elevated hemoglobin and thrombocytosis (resembling essential thrombocythemia), aspirin may reduce thrombotic risk, particularly in those with JAK2 mutations 1

For Patients with Cardiovascular Risk Factors:

• In patients with testosterone-induced erythrocytosis AND established cardiovascular disease or multiple risk factors, low-dose aspirin may provide modest benefit in reducing stroke risk 1
• The ASCEND trial showed a 12% reduction in vascular events with aspirin in high-risk patients, though with increased bleeding risk 1

For Patients Without Additional Risk Factors:

• For patients with isolated testosterone-induced erythrocytosis without additional cardiovascular risk factors, aspirin is not clearly indicated 1
• Recent trials (ARRIVE, ASPREE) found no benefit of aspirin for primary prevention in low-risk individuals 1

Dosing Considerations

• If aspirin is indicated, the lowest effective dose (81-100 mg daily) should be used to minimize bleeding risk 1
• In patients with very high platelet counts or evidence of inadequate 24-hour platelet inhibition, twice-daily low-dose aspirin (81-100 mg BID) may provide better thromboxane suppression 2
• Higher doses of aspirin (>100 mg) have not demonstrated improved efficacy but do increase bleeding risk 1

Monitoring and Safety Considerations

• Monitor for signs of bleeding, particularly gastrointestinal bleeding, which occurs at higher rates with aspirin use 1
• Regularly assess hematocrit levels and consider phlebotomy as the primary intervention when hematocrit exceeds 45% 1
• In patients with platelet counts >1,000×10^9/L, aspirin should be used with caution due to potential acquired von Willebrand syndrome and increased bleeding risk 1

Clinical Algorithm for Decision Making

1. First, ensure hematocrit is maintained <45% through appropriate testosterone dosing and/or phlebotomy 1
2. Assess cardiovascular risk profile:
   • For patients with established cardiovascular disease: Consider low-dose aspirin (81-100 mg daily) 1
   • For patients with multiple cardiovascular risk factors: Consider low-dose aspirin 1
   • For patients with no additional risk factors: Aspirin generally not indicated 1
3. Evaluate for myeloproliferative features:
   • If features of PV or ET are present: Consider low-dose aspirin plus appropriate cytoreductive therapy if indicated 1
4. Monitor response:
   • If aspirin is initiated, assess for bleeding complications and continued need based on hematocrit control 1
   • Consider twice-daily dosing if evidence suggests inadequate 24-hour platelet inhibition 2