title: Defective thrombus formation in mice lacking coagulation factor XII.
abstract: 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.
authors: Institute of Clinical Biochemistry and Pathobiochemistry, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Würzburg, 97078 Würzburg, Germany. thomas@renne.net
authors: Thomas
authors: T
authors: Renné
authors: Miroslava
authors: M
authors: Pozgajová
authors: Sabine
authors: S
authors: Grüner
authors: Kai
authors: K
authors: Schuh
authors: Hans-Ulrich
authors: HU
authors: Pauer
authors: Peter
authors: P
authors: Burfeind
authors: David
authors: D
authors: Gailani
authors: Bernhard
authors: B
authors: Nieswandt
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D003094:Collagen / Q000008:administration & dosage; D004837:Epinephrine / Q000008:administration & dosage; D015942:Factor VIIa / Q000378:metabolism; D005175:Factor XII Deficiency / Q000235:genetics / Q000378:metabolism*; D015956:Factor XIIa / Q000235:genetics / Q000378:metabolism*; D006470:Hemorrhage / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D013923:Thromboembolism / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage
chemical_list: D014662:Vasoconstrictor Agents; D003094:Collagen; D015942:Factor VIIa; D015956:Factor XIIa; D004837:Epinephrine