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Altered platelet function detected by flow cytometry. Effects of coronary artery disease and age
C J Knight1, M Panesar, C Wright
1Department of Cardiology, Royal Brompton Hospital, London, UK.
Insights
Coronary artery disease impairs platelet aggregation and degranulation, with atherosclerosis worsening these responses beyond normal aging effects. This study highlights altered platelet function in patients with cardiovascular disease.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Platelet Physiology
Background:
- Platelet activation and responsiveness are crucial in cardiovascular health.
- Aging and coronary artery disease (CAD) may independently affect platelet function.
- Understanding these changes is vital for managing cardiovascular risk.
Purpose of the Study:
- To investigate platelet activation state and responsiveness to agonists in patients with CAD.
- To compare platelet function in CAD patients with age-matched controls and young healthy subjects.
- To determine if atherosclerosis exacerbates age-related changes in platelet function.
Main Methods:
- Whole-blood flow cytometry was employed to assess platelet markers.
- Measurements included fibrinogen binding, P-selectin, GPIb, and GPIIb-IIIa expression.
- Platelets were analyzed at rest and upon stimulation with ADP and thrombin.
Main Results:
- CAD patients showed lower basal P-selectin expression compared to age-matched controls.
- Stimulated platelets from CAD patients exhibited reduced fibrinogen binding.
- Younger subjects had higher agonist-induced fibrinogen binding and P-selectin expression than both older groups.
Conclusions:
- Atherosclerosis significantly impairs platelet aggregatory responses (fibrinogen binding) beyond age-related decline.
- Platelet degranulation (P-selectin expression) is impaired in CAD patients, particularly compared to younger individuals.
- These findings suggest a distinct impact of CAD on platelet function independent of age.
Abstract:
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 with 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 ex vivo and platelet responsiveness to physiological agonists in vitro. Peripheral blood samples were analyzed for bound fibrinogen and expression of P-selectin, GPIb, and GPIIb-IIIa at rest and in response to ADP (0.1 to 10 mumol/L) and thrombin (0.02 to 0.32 mu/mL). No significant differences were seen in the basal levels of fibrinogen binding between any of the groups, but P-selectin expression was significantly lower in patients compared with age-matched control subjects (P = .0005). When stimulated with agonists, patients' platelets had significantly decreased fibrinogen binding (P < .03) but no difference in P-selectin expression compared with the age-matched group. Both agonist-induced fibrinogen binding and P-selectin expression were, however, higher in the young subjects compared with either the older control group or the patients (P < .05). GPIb and GPIIb-IIIa expression were lowest in the patients with angina 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 cohort (n = 12). In conclusion, atherosclerosis impairs platelet aggregatory 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 comparison with younger subjects, not age-matched controls.