Should I start cytoreductive treatment in a patient with probable essential thrombocythemia (ET), thrombocytosis, and a history of peripheral vascular disease (PVD) with ongoing antiplatelet therapy with Aspirin (Acetylsalicylic acid) and Plavix (Clopidogrel)?

Cytoreductive Treatment for Essential Thrombocythemia with PVD

Cytoreductive therapy should be initiated for this patient with JAK2-positive essential thrombocythemia (ET) who has peripheral vascular disease and is on dual antiplatelet therapy, as this represents a high-risk scenario with increased thrombotic risk.

Risk Assessment and Classification

• This patient has high-risk ET based on:

  • History of peripheral vascular disease (PVD) with stent placement (prior thrombotic event) 1
  • JAK2 V617F mutation (increases thrombotic risk) 1
  • Ongoing tobacco use (additional vascular risk factor) 1
  • Persistent thrombocytosis (platelets 622,000) 1

• The revised International Prognostic Score of Thrombosis for ET (IPSET-Thrombosis) classifies patients with prior thrombosis as high-risk, requiring cytoreductive therapy 1

Rationale for Cytoreductive Therapy

• Cytoreductive therapy is recommended for high-risk ET patients to reduce thrombotic complications 1
• The combination of ET with PVD and dual antiplatelet therapy (ASA and Plavix) creates a complex situation with both increased thrombotic and bleeding risks 1
• Cytoreductive therapy helps normalize platelet counts, which can:
  • Reduce thrombotic risk 1, 2
  • Potentially decrease bleeding risk associated with dual antiplatelet therapy 1

Treatment Recommendations

First-line Therapy:

• Hydroxyurea is the recommended first-line cytoreductive agent for this patient 1, 2
• Target platelet count should be <400 × 10^9/L to reduce thrombotic risk while monitoring for cytopenias 1
• Continue aspirin and clopidogrel for secondary prevention of vascular events given the history of PVD with stent placement 1

Alternative Options (if hydroxyurea intolerance/resistance develops):

• Pegylated interferon alfa could be considered, especially for younger patients 1, 3
• Anagrelide is another alternative for ET patients with hydroxyurea intolerance 1, 4

Monitoring Recommendations

• Regular monitoring of complete blood counts to assess response to therapy 1
• Monitor for signs of hydroxyurea intolerance or resistance 1
• Assess for bleeding complications, especially given dual antiplatelet therapy 1
• Continue to address modifiable risk factors, particularly smoking cessation 1

Special Considerations

• Bleeding risk is increased with the combination of thrombocytosis and dual antiplatelet therapy 1
• Normalization of platelet counts may help mitigate this bleeding risk 1
• The patient's ongoing tobacco use significantly increases thrombotic risk and should be addressed 1
• Multidisciplinary management with the vascular team is recommended to optimize antiplatelet/anticoagulant strategy 1

Common Pitfalls to Avoid

• Delaying cytoreductive therapy in high-risk ET patients increases thrombotic risk 1, 2
• Excessive cytoreduction can lead to cytopenias; monitor blood counts regularly 1
• Failure to address modifiable risk factors like smoking 1
• Not considering the increased bleeding risk with dual antiplatelet therapy in the setting of thrombocytosis 1

By initiating cytoreductive therapy with hydroxyurea while continuing dual antiplatelet therapy, you can help reduce both the thrombotic risk from ET and PVD while potentially decreasing the bleeding risk associated with the combination of thrombocytosis and dual antiplatelet therapy.