Von Willebrand Factor, Factor VIII, and Other Acute Phase Reactants as Biomarkers of Inflammation and Endothelial Dysfunction in Chronic Graft-Versus-Host Disease

Abstract

Chronic graft-versus-host disease (cGvHD) is an immune mediated late complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Discovery of adequate biomarkers could identify high-risk patients and provide an effective pre-emptive intervention or early modification of therapeutic strategy, thus reducing prevalence and severity of the disease among long-term survivors of alloHSCT. Inflammation, endothelial injury, and endothelial dysfunction are involved in cGvHD development. Altered levels of acute phase reactants have shown a strong correlation with the activity of several immune mediated disorders and are routinely used in clinical practice. Since elevated von Willebrand factor (VWF) and factor VIII (FVIII) levels have been described as acute phase reactants that may indicate endothelial dysfunction and inflammation in different settings, including chronic autoimmune diseases, they could serve as potential candidate biomarkers of cGvHD. In this review we focused on reported data regarding VWF and FVIII as well as other markers of inflammation and endothelial dysfunction, evaluating their potential role in cGvHD.

Intracardiac thrombosis in the three-year-old boy with normal left ventricle systolic function in MIS-C associated with COVID-19

“…[1][2][3][4] On the other hand, increased IL-6 and other cytokines establish a prothrombotic state by disabling the natural anticoagulants. 8 Consequently, our patient had a transient hypercoagulable state, likely secondary to the recent SARS-CoV-2 infection. To the best of our knowledge, that is the first case of a three-year-old boy with intracardiac thrombosis in LV with normal systolic function during MIS-C associated with COVID-19.…”

“…Factor VIII and von Willebrand (VWF) have previously been described as acute phase reactants. 8 , 9 Strong independent associations have been proved between elevated FVIII and an increased risk of arterial thrombosis. 8 , 9 Although endothelial cells produce FVIII and VWF, SARS-CoV-2 might induce their accelerated synthesis acting on endothelial ACE-2 receptors.…”

“… 8 , 9 Strong independent associations have been proved between elevated FVIII and an increased risk of arterial thrombosis. 8 , 9 Although endothelial cells produce FVIII and VWF, SARS-CoV-2 might induce their accelerated synthesis acting on endothelial ACE-2 receptors. Coagulation factor XII (FXII, Hageman factor) is a plasma protease that initiates the procoagulant and proinflammatory contact system.…”

Human Periodontal Ligament Stem Cell and Umbilical Vein Endothelial Cell Co-Culture to Prevascularize Scaffolds for Angiogenic and Osteogenic Tissue Engineering

“…vWF is a multimeric adhesive glycoprotein which synthesized and secreted by endothelial cells [28]. It is a marker of endothelial injury and dysfunction [29]. In vitro and in vivo studies have proved that lack of vWF led to enhanced vascularization [30].…”

Perioperative Coagulation Profile in Major Liver Resection for Cancer: A Prospective Observational Study

“…36 After all, hypercoagulability in HCC has been associated with increased risk of portal vein thrombosis even in early stages of liver disease. 37 The vWF and FVIII are acute phase reactants and elevated levels could be attributed to endothelial cell activation 38,39 , which promotes procoagulant activity and prothrombotic…”