Contact system revisited: an interface between inflammation, coagulation, and innate immunity

J Thromb Haemost. 2016 Mar;14(3):427-37. doi: 10.1111/jth.13235. Epub 2016 Feb 9.


The contact system is a plasma protease cascade initiated by factor XII (FXII) that activates the proinflammatory kallikrein-kinin system and the procoagulant intrinsic coagulation pathway. Anionic surfaces induce FXII zymogen activation to form proteolytically active FXIIa. Bacterial surfaces also have the ability to activate contact system proteins, indicating an important role for host defense using the cooperation of the inflammatory and coagulation pathways. Recent research has shown that inorganic polyphosphate found in platelets activates FXII in vivo and can induce coagulation in pathological thrombus formation. Experimental studies have shown that interference with FXII provides thromboprotection without a therapy-associated increase in bleeding, renewing interest in the FXIIa-driven intrinsic pathway of coagulation as a therapeutic target. This review summarizes how the contact system acts as the cross-road of inflammation, coagulation, and innate immunity.

Keywords: angioedema; anticoagulation; factor XII; inflammation; polyphosphates; thrombosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angioedemas, Hereditary / blood
  • Angioedemas, Hereditary / immunology
  • Animals
  • Blood Coagulation*
  • Factor XII / metabolism*
  • Hepatocytes / immunology
  • Hepatocytes / metabolism
  • Humans
  • Hypersensitivity / blood
  • Hypersensitivity / immunology
  • Immunity, Innate*
  • Inflammation / blood*
  • Inflammation / immunology*
  • Inflammation Mediators / blood*
  • Inflammation Mediators / immunology*
  • Polyphosphates / blood
  • Signal Transduction
  • Thrombosis / blood
  • Thrombosis / immunology


  • Inflammation Mediators
  • Polyphosphates
  • Factor XII