title: Recombinant human activated factor VII is thrombogenic in a rabbit model of cyclic flow reduction and does not reduce intra-abdominal bleeding.
abstract: Recombinant human activated factor VII (rHuFVIIa) can reduce bleeding but may be associated with arterial thrombosis. We hypothesized that rHuFVIIa would increase the occurrence of cyclic flow reductions (CFR) and reduce intra-abdominal bleeding in an experimental model. An adapted Folts' model of carotid artery lesion and stenosis was used. Twenty four rabbits were randomized to receive rHuFVIIa (group F) or placebo (group P) in a double-blind fashion. A standardized injury to the common carotid artery resulted in CFR and/or thrombosis. Hematological values, coagulation and thromboelastographic (TEG) variables were compared. Intra-abdominal bleeding was evaluated by measuring blood loss from standardized hepatosplenic lesions. The median number (range) of spontaneous CFR [group P: 6 (0-15); group F: 8 (0-16)] was comparable between groups. The number of induced CFR (by "shaking" of the artery) needed to avert thrombosis (group F: 2; group P: 0; p < 0.05) and the incidence of complete carotid artery thrombosis (group F: 3; group P: 0; p < 0.05) were higher in group F. Intra-abdominal bleeding was similar in both groups. TEG analysis demonstrated a hypercoagulable state in both groups but the magnitude of the change was statistically more important in group F. rHuFVIIa increases thrombosis in a rabbit model of carotid artery injury. The bleeding from hepatic and splenic lesions is not reduced by administration of rHuFVIIa despite a hypercoagulable state confirmed by standard TEG analysis.
authors.affiliation: Department of Anesthesiology, CHUM, Hôpital Notre-Dame, Montreal, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Charbonneau
authors.forename: François
authors.initials: F
authors.lastname: Girard
authors.forename: Daniel
authors.initials: D
authors.lastname: Boudreault
authors.forename: Monique
authors.initials: M
authors.lastname: Ruel
authors.forename: Normand
authors.initials: N
authors.lastname: Blais
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Hardy
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001783:Blood Flow Velocity / Q000187:drug effects*; D002341:Carotid Artery Thrombosis / Q000097:blood / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology; D016893:Carotid Stenosis / Q000150:complications; D003029:Coagulants / Q000009:adverse effects*; D004195:Disease Models, Animal; D015942:Factor VIIa / Q000009:adverse effects*; D006400:Hematocrit; D006470:Hemorrhage / Q000097:blood* / Q000517:prevention & control; D006801:Humans; D008099:Liver / Q000601:surgery; D008297:Male; D010976:Platelet Count; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000009:adverse effects; D013154:Spleen / Q000601:surgery; D013916:Thrombelastography; D013997:Time Factors
chemical_list: D003029:Coagulants; D011994:Recombinant Proteins; D015942:Factor VIIa