Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm associated with increased platelet production and activation, leading to a high risk of thrombotic complications. Low-dose aspirin is the standard antiplatelet therapy for thrombosis prevention; however, the accelerated platelet turnover characteristic of ET results in rapid recovery of platelet function, making once-daily aspirin insufficient in many patients. Consequently, twice-daily low-dose aspirin is currently recommended to achieve adequate and sustained platelet inhibition.

For patients intolerant to aspirin, clopidogrel 75 mg/day is the approved alternative. Clopidogrel irreversibly inhibits the platelet P2Y12 receptor, but its pharmacodynamic effect is highly variable because it is a prodrug requiring metabolic activation. Studies in non-ET populations have shown that higher clopidogrel doses (150 mg/day) provide stronger and more consistent platelet inhibition without significantly increasing bleeding risk.

Evidence on clopidogrel use in ET is limited, but available data suggest that standard-dose therapy may result in inadequate platelet inhibition, potentially reducing antithrombotic efficacy. Platelet function testing can identify patients with high residual platelet reactivity ("poor responders"), who may benefit from dose escalation. Therefore, in ET patients requiring clopidogrel therapy, assessment of platelet responsiveness may help optimize treatment, ensuring adequate platelet inhibition and potentially improving protection against thrombotic events.

Inclusion Criteria:

1. Male or female subjects age ≥ 18 years;
2. Confirmed diagnosis of ET according to the 2022 WHO classification criteria30;
3. Patients treated with clopidogrel 75 mg od as antithrombotic prophylaxis since at least 3 weeks, as per the indication of the referring hematologist;
4. Ability to understand the nature of the study and voluntarily provide written informed consent patients whose responsiveness to the standard clopidogrel regimen was determined, based on clinical practice, using the VN-P2Y12 method.

Exclusion Criteria:

1. Platelet count >1,000,000/μL on three separate determinations within the 2 months prior to enrollment;
2. Need for anticoagulant therapy;
3. Concomitant use of other antiplatelet agents;
4. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) (i.e > 3 days per week);
5. Chronic corticosteroid therapy exceeding a daily dose equivalent to prednisone 5 mg

Consecutive Patients with ET, with an approved indication for clopidogrel therapy (i.e., aspirin intolerance) and a documented good or poor response to the standard 75 mg od dose of clopidogrel at maintenance, as assessed by the standard VN-P2Y12 poinr of care, platelet function test.

At least 50 patients will be enrolled, based on the current records of the participating Centers.