In vitro effects of recombinant activated factor VII (rFVIIa) on coagulation of rabbit blood

rFVIIa has been used with variable efficacy in an effort to control bleeding in trauma patients who were unresponsive to standard therapy. This study examined the hemostatic responses to rFVIIa in normal and coagulopathic blood. Anesthetized rabbits were instrumented to monitor vital signs, blood sampling and fluid infusion. After collection of initial (normal) blood samples, animals were subjected to hypothermia (34.5±0.5C°) and ~34% isovolemic blood exchange with either Hextend (n=9) or 5% albumin solution (n=10) to produce coagulopathy. Blood samples were then collected and animals euthanized. rFVIIa (1μg/ml equal to 90μg/kg dose) or saline was added to all samples and coagulation was assessed by thrombelastography. Addition of rFVIIa accelerated the clotting process by decreasing the initial clot reaction time of both normal and coagulopathic blood ( P <0.001). rFVIIa also increased clot formation rate (α angle, 14%, P <0.001) and maximum clot strength (5%, P <0.001 ) of normal blood, but increased only α angle in albumin diluted (6%, P =0.04) and had no effect on these parameters of Hextend diluted blood. These data show that addition of rFVIIa alone does not restore normal coagulation of hemodiluted hypothermic blood in rabbits. The results also support clinical practice of combining rFVIIa with other hemostatic products (e.g. FFP) to increase the FVIIa efficacy in coagulopathic patients.