What question did this study set out to answer?

This research aims to determine the necessary level of P2Y12 receptor blockade to effectively inhibit platelet function.

January 1, 2010Thrombosis and Haemostasis

Relationship between degree of P2Y12 receptor blockade and inhibition of P2Y12-mediated platelet function

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Why the study?

Does the active metabolite of prasugrel (R-138727) inhibit platelet function in blood from healthy volunteers?

Population

Blood from healthy volunteers

Comparison

Active metabolite of prasugrel in vitro vs Different concentrations of R-138727 (0-10 microM)

Design

Preclinical

Authors

RBRobert BucklandUmeå University ASAtsuhiro SugidachiDaiichi Sankyo (United Kingdom)JJJoseph A. JakubowskiGeneral / Preventive / Lipids

Discussion

Member takes

Implication

In vitro data indicate ≥80% P2Y12 blockade for consistent platelet inhibition; leaves open clinical assay thresholds and in vivo validation.

Key Points

This research aims to determine the necessary level of P2Y12 receptor blockade to effectively inhibit platelet function.
In vitro studies using the active metabolite of prasugrel (R-138727) with blood from healthy volunteers.
Assessment of P2Y12 receptor number with a 33P-2MeSADP binding assay and platelet aggregation via optical aggregometry.
Flow cytometry was used to measure VASP phosphorylation, annexin V binding, microparticle formation, and P-selectin expression.
A blockade of 60-80% resulted in strong inhibition of platelet aggregation, P-selectin expression, microparticle formation, and VASP.
Higher receptor blockade (>80%) consistently ensured strong inhibition of multiple aspects of platelet function.
Low levels of receptor blockade selectively affected P-selectin expression and aggregation responses to ADP, while VASP phosphorylation required higher blockade (>60%) for significant inhibition.

Structured PICO

Does the active metabolite of prasugrel (R-138727) inhibit platelet function in blood from healthy volunteers?

Population

Blood from healthy volunteers

Intervention

Active metabolite of prasugrel (R-138727) (0-10 microM) in vitro

Comparator

Different concentrations of R-138727 (0-10 microM)

Outcome

Platelet function (assessed by platelet aggregation, VASP phosphorylation, annexin V binding, microparticle formation, and P-selectin expression)surrogate

An 80% or greater P2Y12 receptor blockade is required for consistently strong inhibition of platelet function, which guides the interpretation of assays monitoring P2Y12 antagonists.

Cite This Study

Buckland et al. (2010) studied this question.

synapsesocial.com/papers/6a73854d61762fa209a72d0d https://doi.org/10.1160/th09-11-0770

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Implication

In vitro data indicate ≥80% P2Y12 blockade for consistent platelet inhibition; leaves open clinical assay thresholds and in vivo validation.

Relationship between degree of P2Y12 receptor blockade and inhibition of P2Y12-mediated platelet function

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Relationship between degree of P2Y12 receptor blockade and inhibition of P2Y12-mediated platelet function

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider