Essential Thrombocythemia
Conditions
Brief summary
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.
Interventions
DIAGNOSTIC_TESTVerifyNow P2Y12 assay
The VerifyNow® system is a commercially available, CE-certified point-of-care device developed to measure P2Y12 receptor-mediated platelet aggregation in whole blood by turbidimetric-based optical detection in patients treated with clopidogrel or other P2Y12 inhibitors.
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pharmacodynamic effectiveness of different clopidogrel dosing | 15 days | To assess the pharmacodynamic effectiveness of an optimised clopidogrel dosing (75 mg bid) in ET patients with documented poor responsiveness to 75 mg od. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| proportion of patients ET treated with standard-dose clopidogrel | 15 days | To estimate the proportion of patients ET treated with standard-dose clopidogrel (75 mg once daily) who exhibit poor pharmacodynamic response to clopidogrel across |
| consistency over time of pharmacodynamic response | 15 days | To assess the consistency over time of pharmacodynamic response in patients who are documented as good responders to clopidogrel 75 mg once daily with validated platelet function assays. |
Countries
Italy
Contacts
CONTACTElena Rossi
PRINCIPAL_INVESTIGATORElena Rossi
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Outcome results
None listed