# Study on the Mechanism of the Adrenaline-Evoked Procoagulant Response in Human Platelets

## TL;DR

This study explores how adrenaline causes platelets to become more procoagulant by exposing phosphatidylserine, identifying key mechanisms and potential control strategies.

## Contribution

The study identifies ion exchangers, ADP, GPIIb/IIIa signaling, and PI3-K as key mechanisms in adrenaline-induced platelet procoagulant activity.

## Key findings

- Blocking sodium and calcium influx via NHE and NCX significantly reduces PS exposure.
- PI3-K inhibition and cAMP elevation effectively limit adrenaline-evoked PS exposure.
- GPIIb/IIIa antagonists and ADP receptor blockers moderately inhibit PS exposure.

## Abstract

Adrenaline has recently been found to trigger phosphatidylserine (PS) exposure on blood platelets, resulting in amplification of the coagulation process, but the mechanism is only fragmentarily established. Using a panel of platelet receptors’ antagonists and modulators of signaling pathways, we evaluated the importance of these in adrenaline-evoked PS exposure by flow cytometry. Calcium and sodium ion influx into platelet cytosol, after adrenaline treatment, was examined by fluorimetric measurements. We found a strong reduction in PS exposure after blocking of sodium and calcium ion influx via Na+/H+ exchanger (NHE) and Na+/Ca2+ exchanger (NCX), respectively. ADP receptor antagonists produced a moderate inhibitory effect. Substantial limitation of PS exposure was observed in the presence of GPIIb/IIIa antagonist, phosphoinositide-3 kinase (PI3-K) inhibitors, or prostaglandin E1, a cyclic adenosine monophosphate (cAMP)-elevating agent. We demonstrated that adrenaline may develop a procoagulant response in human platelets with the substantial role of ion exchangers (NHE and NCX), secreted ADP, GPIIb/IIIa-dependent outside-in signaling, and PI3-K. Inhibition of the above mechanisms and increasing cytosolic cAMP seem to be the most efficient procedures to control adrenaline-evoked PS exposure in human platelets.