Targeting Raised von Willebrand Factor Levels in Liver Diseases: Opening Up Newer Therapeutic Avenues

Abstract

<jats:p>Raised levels of the blood coagulation protein von Willebrand factor (VWF) are now recognised to be important in patients with liver disease. The markedly raised plasma VWF levels in patients with acute liver failure and acute-on-chronic liver failure may contribute to the pathogenesis of liver failure, and of multi-organ failure, by impeding microcirculatory perfusion in the liver and the other affected vital organs. In this review, the authors present a brief introduction to VWF biology, discuss the ability of raised plasma VWF levels to accurately predict survival in different syndromes of liver diseases, speculate why plasma VWF levels are raised in liver failure syndromes, and examine the therapeutic potential of VWF-lowering therapies in these scenarios.</jats:p>

Targeting raised von Willebrand factor levels and macrophage activation in severe COVID-19: Consider low volume plasma exchange and low dose steroid

“…Baseline VWF antigen levels were raised 3.2-4.7 fold above ULN and predicted poor outcome over the next 7-8 days in patients with acute liver injury/ failure [3] and acute on chronic liver failure [4]. The large sized high molecular weight VWF multimers (5000-10,000 kDa in size), the main circulating form in health, cannot be removed on hemodialysis, which removes molecules < 60 kDa in size [5]. Plasma exchange removes molecules regardless of size.…”

Reticuloendothelial activation correlates with disease severity and predicts mortality in severe alcoholic hepatitis

“…The impaired perfusion in hepatic microcirculation as the reticuloendothelial cells enlarge and compromise the sinusoidal lumen may result in liver failure. Treatment to ameliorate reticuloendothelial system activation may improve the microcirculatory impedance in these situations, may reverse organ failure and improve survival [15]. Dynamic changes in reticulo-endothelial activation, with specific treatment strategies, such as plasma exchange, need to be further explored.…”

“…How to explain this? The raised plasma VWF levels may be due to increased VWF release (from endothelial cells or platelets) or due to reduced VWF clearance or both [15]. VWF is cleared by macrophages [16].…”

Recognizing Dysfunctional Innate and Adaptive Immune Responses Contributing to Liver Damage in Patients With Cirrhosis

“…The exact mechanism is not well understood at present. Overwhelmed scavenging capacity of reticulo - endothelial cells may lead to inflammatory debris clogging the liver sinusoids, reduce perfusion in liver microcirculation and aggravate liver failure in these patients 43 .…”

“…Plasma exchange improves transplant free survival in patients with acute liver failure 64 , 65 , 66 and ACLF 66 , 67 , 68 , 69 , 70 , 71 . The beneficial effect of plasma exchange in these liver disorders with predominant innate immune response may be by attenuating innate immune activation and removing inflammatory debris including macromolecules like VWF 43 .…”