A new animal model of thrombophilia confirms that high plasma factor VIII levels are thrombogenic.
The thrombotic risk associated with elevated plasma levels of clotting factor VIII (FVIII) was investigated in a mouse model of thrombophilia.
After the intravenous injection of recombinant human FVIII and/or of purified FVIII-free human von Willebrand factor (vWF), a controlled mild injury was inflicted on the carotid artery of FVB mice by irradiation with filtered green light in combination with intravenous injection of the dye rose bengal.
Formation of a platelet-rich thrombus was continuously monitored for 40 min via transillumination and the thrombus size was measured via image analysis.
Administration of recombinant human FVIII at 40 mug/kg led to initial FVIII plasma activities equivalent to 250% of normal human plasma FVIII activity and significantly enhanced thrombus size.
Immunohistochemical staining illustrated the accumulation of FVIII within the thrombi.
Human vWF. even at 10 mg/kg, had no effect on thrombus formation.
The thrombotic tendency induced by FVIII was significantly inhibited by the administration of human vWF in a dose-dependent manner.
Separate plasma measurements revealed that human FVIII has comparable affinities for human and murine vWF but that human vWF does not effectively bind murine platelets. (...)
Mots-clés Pascal : Thrombose, Facteur risque, Facteur antihémophilique A, Facteur coagulation, Epidémiologie, Hypercoagulabilité, Modèle animal, Souris, Rodentia, Mammalia, Vertebrata, Animal, Appareil circulatoire pathologie, Vaisseau sanguin pathologie, Hémopathie, Coagulopathie
Mots-clés Pascal anglais : Thrombosis, Risk factor, Factor VIII, Coagulation factor, Epidemiology, Hypercoagulability, Animal model, Mouse, Rodentia, Mammalia, Vertebrata, Animal, Cardiovascular disease, Vascular disease, Hemopathy, Coagulopathy
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 99-0113896
Code Inist : 002B13B03. Création : 16/11/1999.