Aortic stenosis and the haemostatic system

• Published in: Cardiovascular research 2023-06, Vol.119 (6), p.1310-1323
• Main Authors: Trimaille, Antonin, Hmadeh, Sandy, Matsushita, Kensuke, Marchandot, Benjamin, Kauffenstein, Gilles, Morel, Olivier
• Format: Article
• Language: English
• Subjects: Aged, 80 and over; Aortic Valve - pathology; Aortic Valve Stenosis; Hemostatics; Humans; Risk Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; von Willebrand Factor
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvac192

Abstract Aortic stenosis (AS) affects more than 10% of the population over 80 years of age and constitutes a major risk factor for heart failure, thromboembolic stroke, and death. A better understanding of the disease, including its interaction with the haemostatic system, is a prerequisite to develop prophylactic treatments. AS pathogenesis is a dynamic process involving endothelial dysfunction, inflammation, fibrosis, and calcification. Several studies support the interplay between the components of the haemostatic system such as platelets, the coagulation system, von Willebrand factor, and extracellular micro-particles at each pathophysiological stage of AS. Previous reports have evidenced persistent biological activity of the native valve after transcatheter aortic valve replacement and the subsequent development of microthrombosis that may impact the function of the newly implanted valve. Here, we review the current evidence on the interplay between AS and prothrombotic activity, and we emphasize the clinical consequences of these interactions after aortic valve replacement. Graphical Abstract Graphical Abstract Subendothelial thickening represents the early stage of aortic stenosis. Endothelial dysfunction is secondary to biomechanical factors leading to the infiltration of lipids, inflammatory cells, and platelets within the valve, responsible for a subsequent inflammatory reaction. Simultaneously, endothelial dysfunction and inflammation lead to MPs release from endothelium, platelets, and macrophages, vWF infiltration, and TF expression in endothelial cells and macrophages. Overall, these reactions trigger myofibroblastic differentiation of qVIC to aVIC, which promotes ECM remodelling and fibrosis. Platelets also secrete VEGF which stimulates neoangiogenesis within the valvular tissue. ECM remodelling together with MPs, phosphocalcic metabolism disturbance, and osteoblastic differentiation of aVIC to obVIC leads to dystrophic calcification and heterotopic mineralization. In addition to their role in AS progression, different components of the haemostatic system including platelets, TF, vWF, thrombin, fibrin, and MPs exert strong pro-thrombotic actions leading to thrombosis development on the valve surface. ADP, adenosine diphosphate; AS, aortic stenosis; aVIC, activated valvular interstitial cell; Ca, calcium; ECM, extracellular matrix; ICAM-1, intercellular adhesion molecule-1; IL, interleukin; qVIC, quiescent valvular interstitial cell; MPs, mic