Fitusiran mechanism of action. Fitusiran is an siRNA therapeutic conjugated to N-acetylgalactosamine administered via subcutaneous injection. The conjugation to N-acetylgalactosamine enables binding to the asialoglycoprotein receptor, which is expressed exclusively on hepatocytes. Following entry into hepatocytes, fitusiran enters the RISC where it binds the complementary mRNA sequence of AT. This binding results in cleavage of AT mRNA resulting in potent and durable gene silencing. In coagulation, antithrombin serves as a natural brake to activated factor X (Xa) and thrombin (IIa), among other procoagulant factors. The decrease in antithrombin by fitusiran enables continued production of thrombin, resulting in increased fibrin and clot formation. AT, antithrombin; PL, phospholipid; RISC, RNA-induced silencing complex; TF, tissue factor.