Preclinical trauma studies of recombinant factor VIIa.
Preclinical studies in animals and ex vivo human blood have provided a solid rationale for conducting prospective randomized trials in trauma patients. Small animal models have been utilized to study the efficacy of recombinant activated factor VII (rFVIIa; NovoSeven) in treating thrombocytopenic rabbits and for the reversal of anticoagulation. Safety models in the rabbit also exist to test for systemic activation of clotting and pathologic thrombosis. Animal models simulating traumatic injuries in humans have primarily been performed in pigs because of species similarities in terms of coagulation characteristics and the larger internal organs. The pig studies, utilizing human rFVIIa, have shown increased strength of clot formation, decreased bleeding, and improved survival. However, these findings are not uniform and are dependant on the model chosen. All of the animal models described have provided good safety data and suggest that the use of rFVIIa is not associated with systemic activation of coagulation or microthrombosis of end organs.
Schreiber
Martin A
MA
Oregon Health & Science University, Portland, Oregon, USA. schreibm@ohsu.edu
Holcomb
John B
JB
Rojkjaer
Rasmus
R
D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005167:Factor VII / Q000627:therapeutic use*; D015942:Factor VIIa; D006801:Humans; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D013045:Species Specificity; D013552:Swine; D014947:Wounds and Injuries / Q000188:drug therapy*
D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa