Figure 4. Mechanism for the progression from sepsis to liver dysfunction, characterized by neutrophil extracellular traps (NETs) and platelet aggregation. Extravasated platelet aggregation in the space of Disse, initiated by damage to the endothelium, is induced by the formation of NETs or intravasated platelet aggregation in sepsis. Various growth factors released by extravasated platelet aggregation, including TXA2, 5-HT, PAI-1, and TGF-β, induce portal hypertension and promote the progression of liver fibrosis. Furthermore, EPA-derived VEGF-A, TSP-1, s-CD40L, and TGF-β may also contribute to immunoparalysis.