Effect of FXI-ASO on the Coagulation System. FXI-ASO (ISIS 416858) Is a Factor XI (FXI)–targeted Second-generation Antisense Oligonucleotide. Tissue damage after surgery exposes tissue factor and results in the release of DNA, RNA, and inorganic polyphosphate from damaged cells and from activated platelets and neutrophils. Tissue factor binds factor VIIa and initiates the extrinsic pathway of coagulation, whereas DNA, RNA, and polyphosphate activate factor XII and initiate the intrinsic pathway of coagulation. FXI–targeted antisense oligonucleotide attenuates the intrinsic pathway by binding to factor XI messenger RNA (mRNA) in the liver, which results in ribonuclease H1 (RNase H1) –mediated degradation of FXI messenger RNA, thereby preventing protein synthesis and reducing circulating FXI levels.From The New England Journal of Medicine, Harry R. Büller, Claudette Bethune, Sanjay Bhanot, et al, Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis, Volume 372, Page 233 Copyright © 2015 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.