The P2Y12 receptor is a protein receptor found on the surface of platelets, which are small blood cells involved in blood clotting. It belongs to the family of P2Y receptors that are activated by nucleotides, particularly adenosine diphosphate (ADP). The P2Y12 receptor plays a crucial role in platelet activation and aggregation, which are essential processes in the formation of blood clots.
P2Y12 belongs to the Gi class of a group of G protein-coupled (GPCR) purinergic receptors and is a chemoreceptor for adenosine diphosphate (ADP).
The P2Y family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders. Two transcript variants encoding the same isoform have been identified for this gene.
Clinical significance
The drugs, clopidogrel (Plavix), prasugrel (Efient, Effient), ticagrelor (Brilinta), and cangrelor (Kengreal) bind to this receptor and are marketed as antiplatelet agents.
P2Y12 inhibitors do not change the risk of death when given as a pretreatment prior to routine percutaneous coronary intervention (PCI) in people who have had a non-ST-elevation myocardial infarction (NSTEMI). They do however increase the risk of bleeding and decrease the risk of further cardiovascular problems. Thus their routine use in this context is of questionable value.
In patients undergoing primary PCI for an ST-segment elevation myocardial infarction (STEMI), a P2Y12 inhibitor should be administered as soon as possible. The use of clopidogrel in particular has been shown to improve morbidity and mortality endpoints including cardiovascular death, recurrent MI, and stroke at 30 days after PCI.
There is wide variability in the reported incidence of perioperative thromboembolic (0-14%) and hemorrhagic (0-11%) complications after Pipeline Embolization Device (PED) procedures for cerebral aneurysm treatment, which could be partly due to differences in patient response to the P2Y12 receptor antagonist administered while the PED endothelializes.
Two hundred thirty-one patients with 248 cerebral aneurysms treated with the Pipeline embolization device (PED) were retrospectively identified. Patients were started on dual-antiplatelet treatment at least 10 days before the intervention. P2Y12 Reaction Units (PRU) values were checked. Univariate and multivariate logistic regression were performed. Youden Indices were calculated to determine cutoffs for optimal PRU values.
Mean patient age was 57 years. Mean last preprocedural PRU was 132 (range: 1-382). The combined rate of major hemorrhagic complications (4%) and major thromboembolic complications (5.6%) was 9.6%. Analysis using Youden indices suggested an optimal PRU range of 70 to 150 with higher odds of complications outside this range (P = .01, odds ratio [OR] = 3 [1.2-7.5]). PRU <60 was a significant predictor of hemorrhagic complications (P = .04, OR = 2.45 [1.01-5.9]) and PRU >240 was a significant predictor of any thromboembolic complication (P = .04, OR = 3.6 [1.04-12]) and cerebral thromboembolic complications (P = .02, OR = 4 [1.2-14]).
Target preoperative PRU values should be between 60 and 240 and ideally between 70 and 150. Values below this range and above it carry higher odds of hemorrhagic and thromboembolic complications, respectively 1).
When platelets are exposed to tissue injury or damaged blood vessels, they become activated and release ADP. ADP binds to the P2Y12 receptors on neighboring platelets, leading to a series of intracellular signaling events. This activation results in increased platelet aggregation, where platelets clump together to form a plug at the site of injury, preventing excessive bleeding.
However, excessive platelet activation and aggregation can also lead to the formation of unwanted blood clots, which can block blood flow in blood vessels and cause serious conditions like heart attacks and strokes. To prevent these events, medications that inhibit the P2Y12 receptor have been developed to reduce platelet activity and decrease the risk of harmful blood clot formation.
Antiplatelet drugs that target the P2Y12 receptor, such as prasugrel and clopidogrel, work by blocking the receptor's action. These drugs are commonly prescribed to patients with acute coronary syndrome (ACS) or those who have undergone percutaneous coronary intervention (PCI) with stent placement to reduce the risk of blood clot formation and subsequent cardiovascular events.
The P2Y12 receptor is an important therapeutic target in the management of cardiovascular diseases, and its inhibition has proven to be effective in reducing the risk of clot-related complications in high-risk patients. However, the use of P2Y12 receptor inhibitors requires careful monitoring, as excessive platelet inhibition can increase the risk of bleeding. Patients prescribed these medications should follow their healthcare provider's instructions closely and promptly report any signs of bleeding or unusual bruising.