More, More, More: Reducing Thrombosis in Acute Coronary Syndromes Beyond Dual Antiplatelet Therapy—Current Data and Future Directions

To Have and Have Not: Intrinsic Platelet Hyperreactivity?

“…This ADP receptor is, therefore, considered the gatekeeper of platelet activation state. It is, therefore, to date the main therapeutic target during ACSs to prevent thrombus growth and improve the clinical outcome for patients . One originality of the present results is to suggest that the activity of the ADP pathway predicts adverse cardiovascular events in healthy volunteers.…”

“…The key role of thrombus formation was identified several years ago and is considered not only critical for plaque growth but also as a cause of acute coronary syndrome (ACS). Platelets are key drivers of these events . They have several activation pathways, and some of them have emerged as therapeutic targets during ACS.…”

“…Another critical pathway for platelets is the ADP receptors and, in particular, the P2Y 12 receptor. This receptor is of crucial importance in the second phase of platelet activation and aggregation and is considered the main therapeutic target to prevent thrombus formation during ACS and percutaneous coronary interventions . During the past decade, several investigators have demonstrated that, in patients experiencing an ACS, the outcome of percutaneous coronary interventions was dependent on the level of P2Y 12 activity undertreatment, as measured by various platelet assays.…”

“…On the other hand, the P2Y 12 ‐ADP receptor is critical for the generation of platelet‐mediated thrombus. It triggers platelet adhesion/activation, thrombus growth, and stabilization but also modulates the inflammatory response . It also triggers a positive feedback loop in which nearby platelets are recruited in the thrombus.…”

TxA 2 Receptor‐Based Vaccination: A Novel Potential Therapeutic Approach to Limit Thrombosis

“…Apart from thrombin, activated platelets also release ADP and arachidonic acid as secondary mediators that potentiate platelet activation and aggregation. The platelet activation and aggregation cascade is initiated by a variety of platelet receptors including G protein–coupled and other transmembrane receptors, such as protease‐activated receptors (PAR1/4), P 2 Y 12 , glycoprotein (GP) VI and Ib/IX/V, integrin αIIbβ3, and thromboxane A 2 (TxA 2 ) receptor (TPR) 2. These receptors and other platelet‐signaling molecules have been extensively targeted to identify the novel antithrombotic targets, and these efforts, in fact, led to the development of several small molecule inhibitors 3.…”