ALTERED PLATELET-FUNCTION DETECTED BY FLOW-CYTOMETRY - EFFECTS OF CORONARY-ARTERY DISEASE AND AGE

Platelet activation state and responsiveness to physiological agonists were measured in 65 patients with documented coronary artery disease (54 male and 11 female; mean age, 58 years). Twelve patients (mean age , 52 years), selected at random from the male cohort, were compared wi th 12 age-matched male control subjects (mean age, 52 years) and with 10 normal, young male subjects (mean age, 25 years). Whole-blood flow cytometry was used to measure platelet activation status exvivo and pl atelet responsiveness to physiological agonists in vitro. Peripheral b lood samples were analyzed for bound fibrinogen and expression of P-se lectin, GPIb, and GPIIb-IIIa at rest and in response to ADP (0.1 to 10 mu mol/L) and thrombin (0.02 to 0.32 mu/mL). No significant differenc es were seen in the basal levels of fibrinogen binding between any of the groups, but P-selectin expression was significantly lower in patie nts compared with age-matched control subjects (P=.0005). When stimula ted with agonists, patients' platelets had significantly decreased fib rinogen binding (P<.03) but no difference in P-selectin expression com pared with the age-matched group. Both agonist-induced fibrinogen bind ing and P-selectin expression were, however, higher in the young subje cts compared with either the older control group or the patients (P<.0 5). GPIb and GPIIb-IIIa expression were lowest in the patients with an gina and highest in the young control subjects, with levels in the age -matched control subjects falling between these values. Data from the total patient cohort (n=65) were identical to those in the smaller coh ort (n=12). In conclusion, atherosclerosis impairs platelet aggregatel y responses (fibrinogen binding) over and above the decreased response seen with age. Platelet degranulation (P-selectin expression) is also impaired in patients with coronary artery disease, but only in compar ison with younger subjects, not age-matched controls.