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Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate
Laurent Bonello1, Udaya S Tantry, Rossella Marcucci
1Department of Cardiology, Institut National de la Santè et de la Recherche Médicale Unité Mixte de Recherche 608, Hôpital Universitaire Nord, Faculté de Médecine, Marseille, France.
Insights
Dual antiplatelet therapy with aspirin and clopidogrel reduces ischemic events but high on-treatment platelet reactivity remains a concern. This review defines high platelet reactivity and discusses its future clinical use.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Medicine
Background:
- Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is standard for cardiovascular disease, reducing ischemic events.
- Despite DAPT, recurrent ischemic events, including stent thrombosis, persist as significant clinical challenges.
- Platelet function assays reveal variable P2Y12 inhibition and identify high on-treatment platelet reactivity (HPR) in some patients.
Framework:
- High on-treatment platelet reactivity to adenosine diphosphate (ADP) is consistently linked to adverse clinical outcomes.
- Current guidelines do not routinely recommend platelet function monitoring due to lack of consensus on optimal assays and outcome-proven therapeutic adjustments.
- This review establishes a consensus definition for HPR to ADP across various measurement methodologies.
Implementation:
- Standardizing HPR assessment requires agreement on validated assays and risk-associated cutoff values.
- Further research is needed to demonstrate improved patient outcomes through guided antiplatelet therapy adjustments.
- This consensus aims to facilitate the integration of HPR measurement into clinical decision-making.
Implications:
- Defining HPR provides a standardized metric for risk stratification in patients on clopidogrel therapy.
- Future implementation of HPR testing could personalize antiplatelet treatment strategies.
- Optimizing antiplatelet therapy based on platelet reactivity may reduce recurrent ischemic events and improve cardiovascular patient care.
Abstract:
The addition of clopidogrel to aspirin treatment reduces ischemic events in a wide range of patients with cardiovascular disease. However, recurrent ischemic event occurrence during dual antiplatelet therapy, including stent thrombosis, remains a major concern. Platelet function measurements during clopidogrel treatment demonstrated a variable and overall modest level of P2Y(12) inhibition. High on-treatment platelet reactivity to adenosine diphosphate (ADP) was observed in selected patients. Multiple studies have now demonstrated a clear association between high on-treatment platelet reactivity to ADP measured by multiple methods and adverse clinical event occurrence. However, the routine measurement of platelet reactivity has not been widely implemented and recommended in the guidelines. Reasons for the latter include: 1) a lack of consensus on the optimal method to quantify high on-treatment platelet reactivity and the cutoff value associated with clinical risk; and 2) limited data to support that alteration of therapy based on platelet function measurements actually improves outcomes. This review provides a consensus opinion on the definition of high on-treatment platelet reactivity to ADP based on various methods reported in the literature and proposes how this measurement may be used in the future care of patients.
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