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In the setting of patients with indication to receive dual antiplatelet therapy undergoing surgery or invasive procedures, the risk of perioperative cardiac ischemic events, particularly stent thrombosis, is high, because surgery has a prothrombotic effect and antiplatelet therapy is withdrawn in order to avoid bleeding complications. Cangrelor, an intravenous P2Y12 receptor antagonist, has been tested in a randomized trial as a "bridge" to cardiac surgery from discontinuation of oral P2Y12 receptor antagonists. Thus, a consensus document extended its off-label use in this setting and before non-cardiac surgery. Currently, despite the implementation of a standardized bridging protocol with cangrelor, a residual risk of adverse outcome mainly due to bleeding events, still persist during the perioperative phase. Accordingly, a personalized management driven by platelet reactivity serial measurements and careful assessment of ischemic and bleeding risks has potential to optimize outcomes and costs as compared to a standardized bridging protocol, based on average pharmacodynamic data of oral P2Y12 inhibitors. While specific indications for bridging have been extensively addressed in the aforementioned consensus statement, the aim of the present document is the proposal of a "tailored" clinical decision-making algorithm inspired to the principle of personalized medicine dealing with complex clinical scenarios. [ABSTRACT FROM AUTHOR]

Nitric Oxide (NO) plays a relevant role in regulating platelet recruitment and eNOS is the major isoform known to be expressed in platelets. Polymorphisms in the eNOS gene with a reduced NO availability might affect platelet phenotype. The aim of our study was to evaluate the role of eNOS–786T > C, 894G > T and 4a/4b polymorphisms in modulating platelet phenotype in 1442 acute coronary syndrome (ACS) patients on dual antiplatelet therapy, previously investigated in relation to platelet function. Platelet aggregation on platelet-rich plasma after collagen (2 µg/mL), ADP (10 µM) and arachidonic acid (AA) (1 mM) stimuli and the genetic analysis of eNOS polymorphisms were assessed. In subjects carrying the eNOS 4a and -786C alleles a significantly higher maximal platelet aggregation value after AA was found ( p = 0.02 and p = 0.047, respectively). eNOS 4a but not -786C allele weakly influenced platelet aggregation after collagen stimulus ( p = 0.05). eNOS 4a allele significantly and independently influenced AA-induced platelet aggregation ( p = 0.01). A significantly higher percentage of patients with AA-induced high residual platelet reactivity (RPR) was found in subjects carrying both eNOS 4a and -786C allele ( p = 0.03 and p = 0.04, respectively). At logistic multivariate analysis, the eNOS 4a allele significantly influenced the AA-induced high residual platelet reactivity ( p = 0.02). This study evidences a role for eNOS gene in moderately, but significantly, modulating platelet phenotype in a high-risk population on dual antiplatelet treatment. [ABSTRACT FROM AUTHOR]