Defective thrombus formation in mice lacking coagulation factor XII

J Exp Med. 2005 Jul 18;202(2):271-81. doi: 10.1084/jem.20050664. Epub 2005 Jul 11.


Blood coagulation is thought to be initiated by plasma protease factor VIIa in complex with the membrane protein tissue factor. In contrast, coagulation factor XII (FXII)-mediated fibrin formation is not believed to play an important role for coagulation in vivo. We used FXII-deficient mice to study the contributions of FXII to thrombus formation in vivo. Intravital fluorescence microscopy and blood flow measurements in three distinct arterial beds revealed a severe defect in the formation and stabilization of platelet-rich occlusive thrombi. Although FXII-deficient mice do not experience spontaneous or excessive injury-related bleeding, they are protected against collagen- and epinephrine-induced thromboembolism. Infusion of human FXII into FXII-null mice restored injury-induced thrombus formation. These unexpected findings change the long-standing concept that the FXII-induced intrinsic coagulation pathway is not important for clotting in vivo. The results establish FXII as essential for thrombus formation, and identify FXII as a novel target for antithrombotic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Coagulation* / drug effects
  • Blood Coagulation* / genetics
  • Collagen / administration & dosage
  • Epinephrine / administration & dosage
  • Factor VIIa / metabolism
  • Factor XII Deficiency / genetics
  • Factor XII Deficiency / metabolism*
  • Factor XIIa / genetics
  • Factor XIIa / metabolism*
  • Hemorrhage / genetics
  • Hemorrhage / metabolism
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Mutant Strains
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / genetics
  • Thromboembolism / chemically induced
  • Thromboembolism / drug therapy
  • Thromboembolism / metabolism*
  • Thromboembolism / pathology
  • Vasoconstrictor Agents / administration & dosage


  • Vasoconstrictor Agents
  • Collagen
  • Factor VIIa
  • Factor XIIa
  • Epinephrine