Gut dysbiosis, endotoxemia and clotting activation: A dangerous trio for portal vein thrombosis in cirrhosis.

Liver cirrhosis (LC) is associated with portal venous thrombosis (PVT) in roughly 20% of cirrhotic patients but the underlying mechanism is still unclear. Low-grade endotoxemia by lipopolysaccharides (LPS), a component of outer gut microbiota membrane, is detectable in the portal circulation of LC and could predispose to PVT. LPS may translocate into systemic circulation upon microbiota dysbiosis-induced gut barrier dysfunction, that is a prerequisite for enhanced gut permeability and ensuing endotoxemia. Experimental and clinical studies provided evidence that LPS behaves a pro-thrombotic molecule so promoting clotting and platelet activation. Experiments conducted in the portal circulation of cirrhotic patients showed the existence of LPS-related enhanced thrombin generation as well as endothelial dysfunction, venous stasis, and platelet activation. The review will analyze 1) the pro-thrombotic role of endotoxemia in the context of LC 2) the biological plausibility linking endotoxemia with PVT and 3) the potentially interventional tools to lower endotoxemia and eventually hypercoagulation.