Hemostasis is a physiological process critical for survival. Meanwhile, thrombosis is amongst the leading causes of death worldwide, making antithrombotic therapy one of the most crucial aspects of modern medicine. Although antithrombotic therapy has progressed tremendously over the years, it remains far from ideal, and this is mainly due to the incomplete understanding of the exceptionally complex structural and functional properties of platelets. However, advances in biochemistry, molecular biology, and the advent of ‘omics’ continue to provide crucial information for our understanding of the complex structure and function of platelets, their interactions with the coagulation system, and their role in hemostasis and thrombosis. In this review, we provide a comprehensive view of the complex role that platelets play in hemostasis and thrombosis, and we discuss the major clinical implications of these fundamental blood components, with a focus on hemostatic platelet-related disorders and existing and emerging antithrombotic therapies. We also emphasize a number of questions that remain to be answered, and we identify hotspots for future research.

The adipose tissue has long been thought to represent a passive source of triglycerides and fatty acids. However, extensive data have demonstrated that the adipose tissue is also a major endocrine organ that directly or indirectly affects the physiological functions of almost all cell types. Obesity is recognized as a risk factor for multiple systemic conditions, including metabolic syndrome, type 2 diabetes mellitus, sleep apnea, cardiovascular disorders, and many others. Obesity-related changes in the adipose tissue induce functional and structural changes in cardiac myocytes, promoting a wide range of cardiovascular disorders, including atrial fibrillation (AF). Due to the wealth of epidemiologic data linking AF to obesity, the mechanisms underlying AF occurrence in obese patients are an area of rich ongoing investigation. However, progress has been somewhat slowed by the complex phenotypes of both obesity and AF. The triad inflammation, oxidative stress, and mitochondrial dysfunction are critical for AF pathogenesis in the setting of obesity via multiple structural and functional proarrhythmic changes at the level of the atria. The aim of this paper is to provide a comprehensive view of the close relationship between obesity-induced oxidative stress, inflammation, and mitochondrial dysfunction and the pathogenesis of AF. The clinical implications of these mechanistic insights are also discussed.

Experimental models of unprovoked atrial tachyarrhythmias (AT) in conscious, ambulatory animals are lacking. We hypothesized that the aging, spontaneously hypertensive rat (SHR) may provide such a model. Baseline ECG recordings were acquired with radiotelemetry in eight young (14-wk-old) and eight aging (55-wk-old) SHRs and in two groups of four age-matched Wistar-Kyoto (WKY) rats. Quantification of AT and heart rate variability (HRV) analysis were performed based on 24-h ECG recordings in unrestrained rats. All animals were submitted to an emotional stress protocol (air-jet). In SHRs, carbamylcholine injections were also performed. Spontaneous AT episodes were observed in all eight aging SHRs (median, 91.5; range, 4–444 episodes/24 h), but not in young SHRs or WKY rats. HRV analysis demonstrated significantly decreased low frequency components in aging SHRs compared with age-matched WKY rats ( P < 0.01) and decreased low/high frequency ratios in both young ( P < 0.01) and aging ( P = 0.01) SHRs compared with normotensive controls. In aging SHRs, emotional stress significantly reduced the number of arrhythmic events, whereas carbamylcholine triggered AT and significantly increased atrial electrical instability. This study reports the occurrence of unprovoked episodes of atrial arrhythmia in hypertensive rats, and their increased incidence with aging. Our results suggest that autonomic imbalance with relative vagal hyperactivity may be responsible for the increased atrial arrhythmogenicity observed in this model. We also provide evidence that, in this model, the sympatho-vagal imbalance preceded the occurrence of arrhythmia. These results indicate that aging SHRs may provide valuable insight into the understanding of atrial arrhythmias.

Abnormal plasma concentrations of von Willebrand factor (vWF), a marker of prothrombotic risk, have been found in atrial fibrillation (AF) patients, but the extent of this variation is not clear. This study aimed to investigate the effect of different clinical forms of AF on plasma concentrations of vWF at different levels of the circulatory tree, both intracardiac and extracardiac. Peripheral (Pf), left atrial (LA), and coronary sinus (CS) blood samples were obtained during cardiac catheterization from 52 patients with paroxysmal AF (PAF), 36 with persistent AF (PsAF), and 17 control subjects (Ct) with left-sided accessory pathway Wolff–Parkinson–White syndrome. Plasma concentrations of vWF were determined by immunoturbidimetry. Compared with Ct, patients with PAF had higher LA plasma levels of vWF (P = 0.004), but similar Pf and CS levels (both P > 0.30). In contrast, patients with PsAF had higher plasma concentrations of vWF in Pf (P = 0.04), LA (P < 0.001), and CS (P = 0.04) samples compared with Ct. Left atrial plasma concentrations of vWF in patients with PsAF were also higher than in the PAF group (P = 0.04). Regardless of the clinical form of the arrhythmia, AF patients presented significantly higher plasma concentrations of vWF compared with sinus rhythm controls. Multilevel vWF plasma concentration assessment suggests an association between the clinical evolution of AF and the progression of endothelial dysfunction. Further studies will have to establish the exact mechanisms that link endothelial dysfunction and stroke in the context of AF.