Pathogenesis Of Portal Vein Thrombosis In Liver Cirrhosis: The Role of the ADAMTS13/VWF Unbalance

Increasing evidence shows a potential role of ADAMTS13 deficiency as a risk factor for the high prevalence of portal vein thrombosis (PVT) in cirrhotic patients. This deficiency, due to myofibroblastic transformation of hepatic stellate cells (HSCs), the source of ADAMTS13, is responsible for the prevalence of ultra large molecular weight multimers of von Willebrand factor (UL-VWF) in the hepatic microcirculation. This phenomenon would favor the prohaemostatic function of VWF, which, together with an elevation of coagulation FVIII, which is associated to VWF, could sustain microcirculatory thrombosis in the liver. These phenomena, triggering an increase of the intra-hepatic pressure, would cause a slowdown of the portal flow, favoring the occurrence of PVT. Although this scenario is justified by retrospective observational clinical studies, it will be mandatory to clarify the ADAMTS13 expression in HSCs associated with the activity of plasma ADAMTS13 in different stage of liver diseases. Hence, a prospective clinical trial (ClinicalTrials.gov Identifier: NCT03322696) is ongoing to unravel the linkage between all the actors involved in the complex phenomenon of PVT occurring in cirrhosis.