Von Willebrand factor as a thrombotic and inflammatory mediator in critical illness

Abstract

The endothelial exocytosis of high‐molecular‐weight multimeric von Willebrand factor (vWF) may occur in critical illness states, including trauma and sepsis, leading to the sustained elevation and altered composition of plasma vWF. These critical illnesses involve the common process of sympathoadrenal activation and loss of the endothelial glycocalyx. As a prothrombotic and proinflammatory molecule that interacts with the endothelium, the alterations exhibited by vWF in critical illness have been implicated in the development and damaging effects of downstream pathologies, such as disseminated intravascular coagulation and systemic inflammatory response syndrome. Given the role of vWF in these pathologies, there has been a recent push to further understand how the molecule may be involved in the pathophysiology of related diseases, such as trauma‐induced coagulopathy and acute renal injury, which are also known to develop secondarily to critical illness states. Elucidation of the role of vWF across the broader spectrum of generalized pathologies may provide a basis for the development of novel preventative and restorative measures, while also bolstering the scaffold of more widely used treatments, such as the administration of plasma‐containing blood products.

Trauma-induced coagulopathy

“…However, most patients with TIC have preserved platelet counts and evidence of circulating populations of activated platelets, yet paradoxically impaired ex vivo aggregation responses 117,118 . This phenomenon is described as 'platelet exhaustion' , due to injury and shock 119 and is driven by endothelial release of TF, platelet activating factor and vWF 99,120 that activates platelets beyond what is needed for primary haemostasis at the local sites of injury, thereby creating a pool of activated circulating platelets that are 'spent' or exhausted following the release of their procoagulant and anticoagulant factors. These circulating exhausted platelets cannot contribute to primary haemostasis or ex vivo aggregation assays that require platelets to respond to stimulation 112,119 .…”

Ischemic Stroke, Inflammation, and Endotheliopathy in COVID-19 Patients

“… 9 , 10 A recent study analyzed markers of endothelial cell activation or damage in patients with COVID-19, including soluble P-selectin, soluble thrombomodulin, and VWF, and identified endotheliopathy as a common pathophysiology of COVID-19 disease, particularly as patients become critically ill. 6 Endothelial dysfunction and VWF release can occur in critically ill patients with acute respiratory distress syndrome in the absence of COVID-19. 11 However, our subset of stroke patients with elevated VWF and factor VIII did not suffer a critical illness resulting in intubation, acute respiratory distress syndrome, or sepsis. The majority of our patients had preexisting vascular risk factors, suggesting prior endothelial dysfunction, perhaps rendering them more susceptible to developing an endotheliopathy and thrombosis in the setting of COVID-19.…”

Hypoxia alters the expression of ACE2 and TMPRSS2 SARS-CoV-2 cell entry mediators in hCMEC/D3 brain endothelial cells

“…vWF is produced and secreted by endothelial cells following disturbance or damage ( Lip and Blann, 1997 ). It has been implicated in the development of coagulopathies and systemic inflammatory response ( Plautz et al, 2020 ), and was found increased in severe Covid-19 patients ( Escher et al, 2020 ). IL-6, a pro-inflammatory cytokine, was found to contribute to Covid-19-related hyperinflammatory syndrome ( Hlh Across Speciality Collaboration UK et al, 2020 ) and to correlate with Covid-19 severity ( Han et al, 2020 ; Herold et al, 2020 ).…”