PB0755 - GPVI and CD36 expression predict a prothrombotic platelet phenotype

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

AB

Alexander P. Bye

Lecturer in Pharmacology
University of Reading
Reading, England, United Kingdom

Co-Author(s)

nk

neline kriek

Research Associate
University of Reading
Reading, England, United Kingdom
CK

Carly Kempster

Research Associate
University Of Reading
Reading, England, United Kingdom
Joanne L. Dunster, PhD

Research Fellow
Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University Of Reading
Reading, England, United Kingdom
JM

Joanne Mitchell

Research Fellow
University Of Birmingham
Birmingham, England, United Kingdom
TS

Tanya Sage

Research Technician
University Of Reading
Reading, England, United Kingdom
sR

suzannah Rawlings

Research Associate
University Of Reading
Reading, England, United Kingdom
aW

abigail Whyte

Research Nurse
Royal Berkshire Hospital
Reading, England, United Kingdom
LD

Leanne Dymott

Research Nurse
Royal Berkshire Hospital
Reading, England, United Kingdom
sM

sharon Mark

Research Nurse
Royal Berkshire Hospital
Reading, England, United Kingdom
MB

Mark Brunton

Charge Nurse Cardiology Research
Royal Berkshire Hospital
Reading, England, United Kingdom
JB

Joana Batista

Research Associate
University of Cambridge
Cambridge, England, United Kingdom
HM

Harriet McKinney

Research Associate
University of Cambridge
Cambridge, England, United Kingdom
PT

Patrick Thomas

Research Associate
University of Cambridge
Cambridge, England, United Kingdom
KD

Kate Downes

Lead Scientist for Rare and Inherited Disease
NHS East Genomic Laboratory Hub
Cambridge, England, United Kingdom
NR

Neil Ruperelia

Consultant Interventional Cardiologist
Imperial College Healthcare NHS Trust
London, England, United Kingdom
CM

Charlie McKenna

Consultant Cardiologist
Royal Berkshire Hospital
Reading, England, United Kingdom
CJ

Chris Jones

Associate Professor
University Of Reading
Reading, England, United Kingdom
Amanda J. Unsworth, DPhil

Reader
Manchester Metropolitan University
Manchester, England, United Kingdom

Presenting Author(s)

Jonathan M. Gibbins, PhD

Professor
Institute for Cardiovascular and Metabolic Research, School of Biological sciences, University of Reading, Reading, UK
Reading, England, United Kingdom

Background: Platelet reactivity is a risk factor for cardiovascular events, but the mechanisms of platelet function variance are incompletely understood. This study investigated platelet biomarkers that determine platelet reactivity and thrombus growth that can guide use and development of antiplatelet agents.

Aims: To develop a patient stratification algorithm based on biomarkers that predicts a prothrombotic platelet phenotype.

Methods: Flow cytometric analysis of platelet function variables associated with in vitro thrombus formation were investigated in healthy subjects using linear regression and stepwise linear regression. Biomarkers associated with increased platelet function and thrombus development were validated in a cohort of cardiology patients.

Results: Sensitivity to CRP-XL correlated with in vitro thrombus development (r=0.622, p< 0.01) among healthy subjects (n=23). In a larger second cohort of healthy subjects (n=456), stepwise linear regression identified a three-parameter model based on platelet surface expression of CD36 and GPVI and subject age able to predict sensitivity to CRP-XL (r=0.24, MAE=0.27). Stratification of cardiology patients (n=34) using an algorithm based on these three parameters identified a subgroup of patients with high sensitivity to CRP-XL (p < 0.031) and predicted for increased in vitro thrombus formation (p < 0.037).

Conclusion(s): Sensitivity of the GPVI response is a key determinant of thrombus formation which is in turn dependent on expression of platelet surface GPVI and CD36, as well as the age of the subject. Stratification of patients using these three parameters identifies a subgroup of patients with highly sensitivity GPVI responses and a prothrombotic platelet phenotype. Targeting GPVI and CD36 receptors may provide a more effective antiplatelet strategy for this subset of patients.