High-Dose Epinephrine Enhances Platelet Aggregation at the Expense of Procoagulant Activity

Abstract

Platelet activation is characterized by shape change, granule secretion, activation of fibrinogen receptor (glycoprotein [GP] IIb/IIIa) sustaining platelet aggregation, and externalization of negatively charged aminophospholipids contributing to platelet procoagulant activity. Epinephrine alone is a weak platelet activator. However, it is able to potentiate platelet activation initiated by other agonists. In this work, we investigated the role of epinephrine in the generation of procoagulant platelets. Human platelets were activated with convulxin (CVX), thrombin (THR) or protease-activated receptor (PARs) agonists, epinephrine (EPI), and combination thereof. Platelet aggregation was assessed by light transmission aggregometry or with PAC-1 binding by flow cytometry. Procoagulant collagen-and-thrombin (COAT) platelets, induced by combined activation with CVX-and-THR, were visualized by flow cytometry as Annexin-V-positive and PAC-1-negative platelets. Cytosolic calcium fluxes were monitored by flow cytometry using Fluo-3 indicator. EPI increased platelet aggregation induced by all agonist combinations tested. On the other hand, EPI dose-dependently reduced the formation of procoagulant COAT platelets generated by combined CVX-and-THR activation. We observed a decreased Annexin-V positivity and increased binding of PAC-1 with the triple activation (CVX+THR+EPI) com-pared with CVX+THR. Calcium mobilization with triple activation was decreased with the higher EPI dose (1000 µM) compared with CVX+THR calcium kinetics. In conclusion, when platelets are activated with CVX-and-THR, the addition of increasing concentrations of EPI (triple stimulation) modulates platelet response reducing cytosolic calcium mobilization, decreasing procoagulant activity and en-hancing platelet aggregation.

Biomedical application of TiO2NPs can cause arterial thrombotic risks through triggering procoagulant activity, activation and aggregation of platelets

“…3d). Glycoprotein IIb/IIIa (GPIIb/IIIa) plays a key role in the maintenance of PLT aggregation (Aliotta et al 2021). In addition, P-selectin is an adhesion molecule belonging to the selectin family expressed on PLTs, and activated PLTs express high levels of P-selectin(Yeini and Satchi-Fainaro 2022).…”

Light transmission aggregometry in the diagnosis of thrombocytopathy

“…In vitro however, a number of compounds collectively referred to as platelet aggregation agonists can be used for the same purpose. The panel of platelet aggregation agonists typically used in the diagnosis of PFD includes five compounds: ADP (adenosine diphosphate), arachidonic acid (AA), collagen, ristocetin, and epinephrine [9]. For each agonist the process of aggregation is different; the so-called aggregation profile differs as demonstrated on the time-aggregation curve.…”

“…For each agonist the process of aggregation is different; the so-called aggregation profile differs as demonstrated on the time-aggregation curve. Apart from the basic panel of agonists, sometimes alternative activators from the extended panel of agonists are used and these include, among others: thrombin receptor activating peptide (TRAP) and thrombin, thromboxane A2 (TXA2), as well as its equivalent U46619 and collagen-related peptide (CRP) [9]. The choice of an agonist requires the determination of its optimal concentration (Table 1) to eliminate the influence of individual variability on the test result.…”

Mechanisms Underlying Dichotomous Procoagulant COAT Platelet Generation—A Conceptual Review Summarizing Current Knowledge

“…Common model such as procoagulant COAT platelets are required in order to compare observations between research groups [ 51 ]. However, other agonists (e.g., adenosine diphosphate (ADP) [ 52 ], arachidonic acid [ 52 ], ionophore A23187 [ 36 ], or thrombin receptor activating peptide 6 (TRAP6) [ 52 ]) or inhibitors (e.g., epinephrine [ 53 ] or antibodies [ 36 ]) are also used to assess platelet procoagulant response through different pathways.…”