Recombinant activated factor VII attenuates major arterial bleeding in noncoagulopathic rabbits

• Published in: European journal of anaesthesiology Vol. 28; no. 1; p. 51
• Main Authors: Durand, Marion, Godier, Anne, Notet, Véronique, Hacquard, Marie, Collignon, Olivier, Corbonnois, Gilles, Plénat, François, Carteaux, Jean-Pierre, Lecompte, Thomas
• Format: Journal Article
• Language: English
• Published: England 01.01.2011
• Subjects: Animals; Carotid Arteries - pathology; Disease Models, Animal; Dose-Response Relationship, Drug; Factor VIIa - administration & dosage; Factor VIIa - pharmacology; Hemorrhage - drug therapy; Male; Rabbits; Random Allocation; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Time Factors; Wound Healing
• ISSN: 1365-2346
• DOI: 10.1097/EJA.0b013e32833cf067

Recombinant activated factor VII (rFVIIa), which is used off-label as an adjuvant therapy for uncontrolled and life-threatening bleeding, might also attenuate intractable bleeding related to macrovascular arterial lesions. Here we evaluated the efficacy of rFVIIa in sealing a large arterial wound in haemostatically competent rabbits. Sixty male New Zealand rabbits were randomly divided into vehicle control and 80 and 200 μg kg⁻¹ rFVIIa groups (n = 20 animals each). A standardized wound of the isolated right carotid artery was made in all rabbits with an 18-G catheter. Bleeding, which was limited by mild compression, was assessed every minute. At 5 min, an intravenous bolus of vehicle or human rFVIIa was given and the animals were further observed for 1 h. Efficacy was assessed from the bleeding duration and blood mass lost. Statistical significance was defined as P less than 0.05. All investigators were blinded to the treatment the animals received. The bleeding duration and blood mass lost were significantly reduced in both rFVIIa dosage groups as compared with the vehicle control group. For the vehicle, 80 and 200 μg kg⁻¹ rFVIIa groups, the median bleeding durations were 56 min (range 7-60 min), 15 min (range 5-60 min) and 10 min (range 5-60 min), respectively; and the median blood mass losses were 22.5 g (range 1-58 g), 12 g (range 0-36 g) and 5 g (range 0-31 g), respectively. The prothrombin time was shorter in the rFVIIa groups. Visual inspection of the carotid artery and microscopic analysis of the liver and kidney revealed neither gross thrombi nor entrapped microthrombi in any rabbit. Recombinant FVIIa at 80 or 200 μg kg⁻¹ promoted the sealing of a large and slightly compressed arterial wound in rabbits. These results suggest a potential role for the drug in the management of massive bleeds due to an arterial lesion when surgical intervention is not immediately and readily available. Safety should remain a matter of concern.