Platelet hyperreactivity generalizes to multiple forms of stimulation.
BACKGROUND
Although platelet hyperreactivity constitutes an important cardiovascular risk factor, standardized methods for its measurement are lacking. We recently reported that aggregometry using a submaximal concentration of epinephrine identifies individuals with in vitro platelet hyperreactivity; this hyperreactivity was reproducible on multiple occasions over long periods of time.


OBJECTIVE
To better understand this aberrant reactivity, we studied in a large group of subjects (n = 386) the relationship between healthy individuals' platelet reactivity to epinephrine and their platelet phenotype as measured by other functional assays.


RESULTS
Subjects with hyperreactivity to epinephrine were more likely to exhibit hyperfunction in each major aspect of platelet activity, including adhesion (response to low-dose ristocetin; P < 0.001), activation (surface P-selectin expression and PAC-1 binding after stimulation; P <or= 0.003) and aggregation to other agonists [no agonist, adenosine diphosphate (ADP), arachidonic acid, collagen, collagen-related peptide and ristocetin; P <or= 0.025] and to applied shear stress (PFA-100 and cone-and-plate viscometer; P < 0.05). These differences persisted after adjusting for demographic and hematologic differences between groups. We studied candidate genes relevant to epinephrine-mediated platelet activation and found that hyperreactivity to epinephrine was associated with a polymorphism on the gene (GNB3) encoding the beta-3 subunit of G proteins (P = 0.03).


CONCLUSIONS
Robust aggregation to a submaximal concentration of epinephrine establishes a true hyperreactive platelet phenotype that is 'global' as opposed to agonist specific; detection of this phenotype could be useful for studying patients at risk for arterial thrombosis. The mechanisms underlying hyperreactivity to different types of platelet stimulation may share common signaling pathways, some of which may involve specific G protein subunits.
Yee
D L
DL
Department of Pediatrics, Hematology-Oncology Section, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Bergeron
A L
AL
Sun
C W
CW
Dong
J-F
JF
Bray
P F
PF
D000328:Adult; D001791:Blood Platelet Disorders / Q000235:genetics*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000235:genetics* / Q000502:physiology*; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000235:genetics; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D011110:Polymorphism, Genetic
D044387:GTP-Binding Protein beta Subunits; D004837:Epinephrine