title: The intrinsic pathway of coagulation is essential for thrombus stability in mice.
abstract: Blood coagulation is a highly regulated process involving interactions between platelets, plasma coagulation factors, and the vessel wall. During coagulation in vivo, fibrin formation is thought to be initiated when plasma factor VIIa forms a complex with the membrane protein tissue factor. Coagulation factor XII (FXII, Hageman factor) is required for some in vitro coagulation systems; however, FXII deficiency is not associated with hemorrhage, leading to the conclusion that it is not necessary for hemostasis. We generated FXII-deficient mice to study the contributions of FXII to thrombosis and hemostasis in arterial injury models and in models of acute arterial occlusion. FXII-deficient mice do not experience excessive injury-related bleeding; however, intravital fluorescence microscopy and blood flow measurements in three separate arterial beds revealed a severe defect in formation and stabilization of platelet-rich occlusive thrombi induced by different methods of injuries. Similar findings were observed for mice deficient in factor XI, a substrate of activated FXII. Infusion of human FXII into FXII null mice restored thrombus formation. These findings demonstrate that FXII-mediated fibrin formation is crucial for pathological arterial thrombosis but not for hemostasis and suggest that FXII could be an ideal target for safe anticoagulation.
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry, Julius-Maximilians-University Würzburg, Josef-Schneider Strasse 2, D-97080 Würzburg, Germany. thomas@renne.net
authors.forename: Thomas
authors.initials: T
authors.lastname: Renné
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.forename: David
authors.initials: D
authors.lastname: Gailani
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001779:Blood Coagulation Factors; D005174:Factor XII / Q000502:physiology*; D005175:Factor XII Deficiency; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D013927:Thrombosis / Q000209:etiology*
chemical_list: D001779:Blood Coagulation Factors; D005174:Factor XII