title: Factor XI: hemostasis, thrombosis, and antithrombosis.
abstract: Coagulation factor FXI (FXI), a plasma serine protease zymogen, has important roles in both intrinsic and extrinsic coagulation pathways and bridges the initiation and amplification phases of plasmatic hemostasis. Recent studies have provided new insight into the molecular structure and functional features of FXI and have demonstrated distinct structural and biological differences between activated factor XII (FXIIa)-mediated FXI activation and tissue factor/thrombin-mediated FXI activation. The former is important in thrombosis; the latter is more essential in hemostasis. Activated partial thromboplastin tine (aPTT) artificially reflects FXIIa-initiated intrinsic coagulation pathway in vitro. Conversely, FXIIa-inhibited diluted thromboplastin time assay may reflect tissue factor/thrombin-mediated FXI activation in vivo. Further explication of the genetic mutations of FXI deficiency has improved the understanding of the structure-function relationship of FXI. Besides its procoagulant activity, the antifibrinolytic activity of FXI was well documented in a wealth of literature. Finally, the new emerging concept of inhibiting FXI as a novel antithrombotic approach with an improved benefit-risk ratio has been supported through observations from human FXI deficiency and various animal models. Large- and small-molecule FXI inhibitors have shown promising antithrombotic effects. The present review summarizes the recent advancements in the molecular physiology of FXI and the molecular pathogenesis of FXI deficiency and discusses the evidence and progress of FXI-targeting antithrombotics development.
authors.affiliation: Division of Hematopathology, Mayo Clinic, Rochester, Minnesota 55905, USA. he.rong@mayo.edu
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Shilin
authors.initials: S
authors.lastname: He
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D005172:Factor XI / Q000235:genetics / Q000378:metabolism*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D013927:Thrombosis / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000925:Anticoagulants; D005172:Factor XI