Platelet hyperreactivity generalizes to multiple forms of stimulation.

Area of Science:

• Cardiovascular Research
• Hematology
• Platelet Biology

Background:

• Platelet hyperreactivity is a significant cardiovascular risk factor.
• Standardized methods for measuring platelet hyperreactivity are lacking.
• Epinephrine aggregometry at submaximal concentrations identifies reproducible in vitro platelet hyperreactivity.

Purpose of the Study:

• To investigate the relationship between epinephrine-induced platelet reactivity and other platelet functional assays in healthy individuals.
• To characterize the platelet phenotype associated with epinephrine hyperreactivity.

Main Methods:

• Studied 386 healthy individuals.
• Assessed platelet adhesion, activation, aggregation to various agonists, and response to shear stress.
• Analyzed candidate genes, including GNB3, for associations with epinephrine hyperreactivity.

Main Results:

• Individuals with epinephrine hyperreactivity showed hyperfunction in adhesion, activation, and aggregation to multiple agonists.
• This global hyperfunction extended to responses to shear stress.
• A polymorphism in the GNB3 gene was associated with epinephrine hyperreactivity (P = 0.03).

Conclusions:

• Robust epinephrine aggregation defines a global platelet hyperreactive phenotype, useful for identifying individuals at risk for arterial thrombosis.
• Common signaling pathways, potentially involving G protein subunits, may underlie various forms of platelet hyperreactivity.