Mechanistic implications for the use and monitoring of recombinant activated factor VII in trauma.
As interest in the use of activated recombinant factor VII (rFVIIa) in trauma grows, questions arise regarding how best to monitor rFVIIa therapy and when rFVIIa may be expected to improve hemostasis. Knowledge of the mechanisms of action may be combined with available data on laboratory monitoring and efficacy in various coagulopathic states in coming to clinically relevant conclusions. This review addresses the physiology of hemostasis, placing emphasis on how rFVIIa influences the process by both tissue factor dependent and tissue factor independent mechanisms. This is extended to a mechanistic consideration of how rFVIIa may function under acidotic, hypothermic, and hemodilutional and/or consumptive conditions of trauma related coagulopathy. When these considerations are viewed alongside the available clinical data, it becomes apparent that rFVIIa has potential to improve hemostasis during trauma coagulopathy, within limitations. Common laboratory procedures are discussed with reference to mechanisms of action of rFVIIa and the available clinical data. Although there is no single assay that can predict rFVIIa efficacy in trauma, the prothrombin time (PT) is recommended as a minimum. Although a shortened PT does not predict success, correction of PT into the normal range may be a better indicator. A nonresponding PT appears to indicate that rFVIIa alone will not lead to hemostasis, and that additional blood products and other measures must be applied. Once the patient is more stable, PT and thromboelastography are recommended.
Pusateri
Anthony E
AE
US Army Institute of Surgical Research, Fort Sam Houston, Texas, USA. Anthony.pusateri@amedd.army.mil
Park
Myung S
MS
D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D019411:Clinical Laboratory Techniques; D005167:Factor VII / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D015942:Factor VIIa; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013916:Thrombelastography / Q000379:methods*; D014947:Wounds and Injuries / Q000097:blood / Q000503:physiopathology / Q000628:therapy*
D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa