Cardiac failure is becoming increasingly common with improvements in therapeutic targets in an aging population
[1]. Cardiac failure represents a clinical syndrome with significant morbidity and mortality. The pathophysiology of cardiac failure is a complex mix of structural and functional alterations. However, the exact mechanisms underlying the disease remain poorly defined
[2]. Endothelial dysfunction has been identified as one of the components of cardiac failure pathophysiology, whereby disturbances in coronary microcirculation are thought to contribute to cardiac failure and its progression
[3,4][3][4]. Inflammatory or ischemic endothelial activation results in the release of von Willebrand factor (VWF) from Weibel–Palade bodies held in endothelial cells
[5]. VWF is a large, complex protein that has a crucial role in platelet adhesion and aggregation and is involved in both primary and secondary haemostasis
[6]. VWF exists in plasma as multimers of increasing size, with the largest (high molecular weight; HMW) expressing the greatest functional activity. A deficiency of VWF is associated with a congenital bleeding disorder called von Willebrand disease (VWD). In addition, the loss of VWF can occur in a variety of acquired conditions
[6,7][6][7]. Of note, certain cardiac lesions, particularly aortic stenosis, can elongate VWF multimers in the shear field, resulting in proteolytic loss of the highest molecular weight forms, leading to subsequent loss of VWF activity and resultant bleeding
[8,9][8][9]. VWF activity is controlled through cleavage by a disintegrin and metalloproteinase with thrombospondin type 1 motif-13 (ADAMTS13), also known as VWF-cleavage protease. Elevation of VWF and potential reduction in ADAMTS13 essentially represent biomarkers of endothelial dysfunction, as most recently typified in COVID-19 (Coronavirus Disease 2019)
[10].
Plasma VWF levels can be assessed by means of VWF antigen (VWF:Ag)
[11,12][11][12] and/or a variety of activity assays
[6,11,12][6][11][12]. The most common VWF:Ag assays comprise latex-enhanced immunoassays and enzyme-linked immunosorbent assays
[11,12][11][12]. Activity assays for VWF include measurements of binding to platelet glycoprotein Ib (GPIb), collagen and factor VIII
[11]. However, in the main, studies reporting a single VWF parameter report VWF:Ag levels. VWF:Ag levels reflect both active and inactive VWF. There are over 20 different commercial options for the measurement of VWF:Ag, and publications do not always report the method used
[10]. ADAMTS13 can also be measured as an antigen assay using enzyme-linked immunosorbent assays
[13], or as an activity assay, with FRETS-based assays being common
[13], or by using chemiluminescence
[14] among other procedures
[13]. However, in the main, studies reporting a single ADAMTS13 parameter report activity levels. In total, there are over 20 different commercial options for measurement of ADAMTS13, and publications do not always report the method used
[10].