Epinephrine sensitizes human platelets in vivo and in vitro as studied by fibrinogen binding and P-selectin expression.

Abstract

Epinephrine (Epi) infusion influences platelet activation markers in vivo, but in vitro studies have mainly examined supraphysiologica] Epi concentrations and have yielded conflicting results. In this study whole-blood flowcytometric measurements of platelet fibrinogen binding and P-selectin expression were used to compare enhancement of ADP (0.1 to 10 /irnol/L)-induced platelet activation by Epi infusion in vivo (0.1 and 0.4 nmol • kg" 1 • min" 1 ) and by Epi in vitro (10 and 50 nmol/L) in nine healthy volunteers. ADP caused concentration-dependent increases in the percentage of platelets that bound fibrinogen (from 4.4 ±0.9% to 69.9±4.2%) and that expressed P-selectin (from 4.5±0.5% to 44.2±3.8%). Fibrinogen and P-selectin binding indices (FgBI and PSBI; calculated from mean fluorescence intensity and percentage of positive cells) also increased from 0.18 ±0.03 to 11.70±1.99 for FgBI and from 0.22±0.03 to 2.34±0.29 for PSBI. Epi concentration-dependently enhanced fibrinogen binding and P-selectin expression in vitro (by »»30% at the midportion of the ADP curve at 10 nmol/L Epi; P<.001 for both by ANOVAs). High-dose Epi infusion enhanced FgBI similarly and increased maximal P-selectin expression by 38%. Epi (50 nmol/L in vitro) enhanced platelet activation further, whether samples were taken with or without prior Epi infusion. Total expression of gfycoprotein Ilb/IIIa was unaffected by Epi infusion, but glycoprotein Ib expression per platelet was reduced (/*<.05). These in vivo and in vitro effects of Epi on platelet responses to agonist stimulation indicate a prothrombotic potential for sympathoadrenal activation in humans.

Strenuous but not moderate exercise increases the thrombotic tendency in healthy sedentary male volunteers

“…Exercise induces the release of cathecholamines (12,14,23,28). At high concentrations, epinephrine promotes platelet aggregation, and at low concentrations, it potentiates platelet aggregation induced by other platelet agonists such as ADP or collagen (11). Thus, in flow conditions typical of atherosclerotic arteries, epinephrine has been found to enhance platelet deposition on severely damaged vessel wall and on collagen fibrils (2,18).…”

Increased platelet responsiveness following coronary stenting Heparin as a possible aetiological factor in stent thrombosis

“…Whole blood flow cytometry has been shown previously to be able to detect changes in platelet behaviour in a variety of clinical settings [20] and in response to physiological stress [21] and pharmacological treatment [22] . Despite the sensitivity of the technique, the lack of a measurable rise in platelet activation in peripheral blood samples following PTCA is perhaps not surprising, given the small size of the plaque event and the rapid clearance of activated platelets from the Platelet responsiveness following stenting 1243…”

Platelet Activity, Coagulation, and Fibrinolysis During Exercise in Healthy Males

“…Noradrenaline and adrenaline are likely mediators in exercise-induced platelet activation, because the plasma levels of both catecholamines are elevated Ϸ10-fold in the present stress model 3 and they are known to enhance platelet activity in vivo and in vitro at these levels. 22,23 However, the hypothesis of catecholamine-induced platelet activation has not been tested in experiments involving ␣-adrenoceptor blockade during exercise. Exercise also causes thrombocytosis, and another possible explanation is that platelets that are newly released into the circulation are more responsive to various stimuli.…”