Interaction of von Willebrand factor with blood cells in flow models: a systematic review

Abstract

The presence of blood flow influences the interaction between von Willebrand factor (VWF) and blood cells, affecting characteristics of forming blood clots. The interactions between coagulation and inflammation have mainly been studied in thrombosis models, but it remains unclear whether these interactions might also play a role in reduced bleeding in patients with bleeding disorders. In this systematic review, we provide an overview of the literature investigating the interactions between VWF and blood cells in flow models. For article selection, a systematic search was performed in Embase, Medline-Ovid, Cochrane Library, Web of Science databases, and Google Scholar. After selection, 24 articles were included. These articles describe direct or platelet-dependent interactions between VWF and neutrophils, monocytes, erythrocytes, or lymphocytes under different flow conditions. Almost all the described interactions required the presence of activated platelets. Only erythrocytes, monocytes, and natural killer cells were capable of directly binding the VWF multimers. Overall, interactions between VWF and blood cells mainly occurred in the presence of platelets. Because of the large variation in study design and used flow rates, further research is necessary to compare the results between studies and draw firm conclusions on when and under what conditions these interactions can occur. After our findings, many questions remained unanswered. This review might provide a starting point for future research. Extended knowledge on the influence of blood flow on VWF and blood cell interactions can contribute to improved understanding of the variation in bleeding in patients with bleeding disorders.

Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications

“…In this condition, endothelial-derived ADP may trigger platelet activation, following which receptors such as αIIbβ3 integrins [120], CD40L (CD154) and P-selectin become highly expressed on the surface of ECs [121]. These are important mediators in interactions with fibrinogen and other circulating cells in the blood [122]. As previously mentioned, vWf is released from the endothelial Weibel-Palade bodies into the bloodstream.…”

“…As previously mentioned, vWf is released from the endothelial Weibel-Palade bodies into the bloodstream. In vessels with lower shear stress and the presence of vWf, erythrocytes tend to aggregate, rolling on and adhering to ultralarge vWf multimer strands released from activated ECs [122]. Subsequently, platelets interact with the A1 domain of vWf, resulting in additional platelet binding and platelet activation [123].…”

To Gain Insights into the Pathophysiological Mechanisms of the Thrombo-Inflammatory Process in the Atherosclerotic Plaque

“…In a crucial study [ 103 ] predating the discovery of NETs [ 57 ], a distinct binding between the A1 domain of VWF and histones had been identified, elucidating the purpose of this interaction site on VWF. It has been observed that recombinant ADAMTS13 therapy not only clears VWF from endothelial surfaces, but also removes NETs [ 83 , 84 , 104 , 105 , 106 , 107 ] ( Figure 4 ).…”

“…Figure 4 demonstrates a clear interaction between VWF and and histones both bind to VWF, effectively anchoring NETs in place [100-10 study [103] predating the discovery of NETs [57], a distinct binding betwe main of VWF and histones had been identified, elucidating the purpose of th site on VWF. It has been observed that recombinant ADAMTS13 therapy n VWF from endothelial surfaces, but also removes NETs [83,84,[104][105][106][107] (Fig Histological examination of both animal and human thrombi reveals interwoven fibrin, NETs, and VWF localized in the solid matrix of thrombi. VWF stabilises the thrombus by acting as a bridge between the vessel wall and the NETs.…”