Recombinant activated factor VII efficacy and safety in a model of bleeding and thrombosis in hypothermic rabbits: a blind study

Abstract

To cite this article: Godier A, Mazoyer E, Cymbalista F, Cupa M, Samama C-M. Recombinant activated factor VII efficacy and safety in a model of bleeding and thrombosis in hypothermic rabbits: a blind study. J Thromb Haemost 2007; 5: 244-9.See also Levi M. Recombinant factor VIIa and trauma: treatment that does not leave you in the cold. This issue, pp 242-3.Summary. Background: Recombinant activated factor VII (rFVIIa) is increasingly used to secure hemostasis in hemorrhagic situations in trauma and surgical patients. Hypothermia is often observed in these clinical settings. Objective: To study the efficacy and safety of rFVIIa in hypothermia in a rabbit model of bleeding and thrombosis. Methods: Sixty-nine rabbits were anesthetized, ventilated and monitored for blood pressure, temperature and carotid flow. The Folts model was used: a stenosis (75%) and an injury were carried out on the carotid artery, inducing thrombosis. Blood flow decreased as thrombus size increased until the pressure gradient was such that the thrombus was released and local arterial blood flow was suddenly restored. This is known as a cyclic flow reduction (CFR). After counting baseline CFRs during a 20-min period (P1), rabbits were randomized blindly to one of four groups: normothermic (NT) placebo or rFVIIa (150 lg kg )1 ), hypothermic (HT) (34°C) placebo or rFVIIa. Then CFRs were recorded over a second period (P2). At the end of the experiment, a hepato-splenic section was performed and the amount of blood loss was recorded. After each period, the following were measured: ear immersion bleeding time (BT), hemoglobin, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen. Results: Hypothermia increased BT and blood loss. These effects were reversed by rFVIIa. In NT rabbits, rFVIIa shortened BT but did not reduce blood loss. rFVIIa-treated rabbits bled similarly regardless of temperature. The incidence of CFRs was higher in treated than placebo animals regardless of temperature. rFVIIa decreased PT and aPTT without modifying platelet count or fibrinogen level. Conclusion: Hemostatic efficacy of rFVIIa was maintained in hypothermia. However, the number of CFRs was higher in the rFVIIa-treated group than in the placebo groups, whether for NT or HT rabbits.

von Willebrand Factor as a Biological Sensor of Blood Flow to Monitor Percutaneous Aortic Valve Interventions

“…We developed a new rabbit model of instantaneous, reversible, calibrated supra-AS, adapted from Assad et al 16 and Godier et al 17 (see Methods in the Online Data Supplement). This model allowed the evaluation in the same rabbit, of the dynamic time course of loss and recovery of HMW multimers.…”

Recombinant Activated Factor VII as a Hemostatic Agent in Very Low Birth Weight Preterms With Gastrointestinal Hemorrhage and Disseminated Intravascular Coagulation

“…This could also be demonstrated in animal studies. 34,35 An accumulation of more than 1 of these factors led to a failure of rFVIIa therapy. This observation was also reported in large trauma trials.…”

The influence of coagulation and inflammation research on the improvement of polytrauma care

“…In the same year, it was found that rFVIIa increased the thrombosis rate in a rabbit model of carotid artery injury without reducing bleeding from standardized hepatic and splenic lesions, despite a hypercoagulable state as evidenced by TEG [59]. In a rabbit model of bleeding and thrombosis of the carotid artery, rFVIIa administration decreased bleeding time in both hypothermic or normothermic animals [60]. In 2008, Zhang et al [61] reported that rFVIIa treatment after traumatic brain injury (TBI) in a pig model reduced expansion of hemorrhagic cerebral contusion volume without exacerbating the severity of microclot formation and provided some neuroprotective effect.…”