Int J Burn Trauma 2012;2(3):145-157
Original Article
Acidosis and correction of acidosis does not affect
rFVIIa function in swine
Daniel N Darlington, Bijan S Kheirabadi, Michael R Scherer, Wenjun Z Martini, Andrew P Cap, Michael A Dubick
US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA
Received November 2, 2012; Accepted November 16, 2012; Epub December 5, 2012; Published December 15,
2012
Abstract: Background: Hemorrhagic shock and trauma are associated with acidosis and altered coagulation. A fall
in pH has been reported to attenuate the activity of recombinant activated Factor VII (rFVIIa) in vitro. However, it is
not known if acidosis induced by hemorrhagic shock or infusion of HCl attenuates FVIIa activity in vivo. The purpose
of this study was to determine if acidosis, induced by two methods, affects recombinant FVIIa (rFVIIa) activity in
swine, and if correction of the pH restores rFVIIa activity to normal. Methods: Acidosis was induce in anesthetized
swine in two separate models: 1) HCl infusion (n=10) and 2) hemorrhage/hypoventilation (n=8). Three groups per
model were used: Control (pH7.4), Acidosis (arterial pH7.1) and Acidosis-Corrected (bicarbonate infusion to return
pH from 7.1 to 7.4). Pigs were then injected with rFVIIa (90 μg/kg) or vehicle (saline) at target pH and arterial blood
samples were taken for measurement of coagulation function, including Thromboelastography -TEG, Thrombin Generation,
Activated Clotting Time, Prothrombin Time, activated Partial Thromboplastin Time, Fibrinogen Concentration
and Platelet count before and 5min after injection of rFVIIa. Results: Acidosis led to a hypocoagulation as
measured by almost all coagulation parameters in both models. Furthermore, the change in coagulation function
produced after infusion of rFVIIa was not different between control, acidosis and acidosis-corrected groups for all
coagulation parameters measured. Conclusion: Acidosis associated with hemorrhagic shock or HCl infusion led to a
hypocoagulation that was not corrected with bicarbonate infusion. Furthermore, acidosis did not affect rFVIIa function,
and correction of the acidosis with bicarbonate had no effect on rFVIIa function in these models. This suggests
that in vivo acidosis did not diminish rFVIIa function.
Keywords: Hemorrhage, acidosis, hypoventilation, hypocoagulation, thromboelastography, thrombin generation,
rotational thromboelastogram, fibrinogen, platelets, coagulation parameters, recombinant factor VIIa
Address correspondence to:
Daniel N Darlington
US Army Institute of Surgical Research
Fort Sam Houston, TX 78234, USA.
E-mail: Daniel.darlington@amedd.army.mil
Original Article
Acidosis and correction of acidosis does not affect
rFVIIa function in swine
Daniel N Darlington, Bijan S Kheirabadi, Michael R Scherer, Wenjun Z Martini, Andrew P Cap, Michael A Dubick
US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA
Received November 2, 2012; Accepted November 16, 2012; Epub December 5, 2012; Published December 15,
2012
Abstract: Background: Hemorrhagic shock and trauma are associated with acidosis and altered coagulation. A fall
in pH has been reported to attenuate the activity of recombinant activated Factor VII (rFVIIa) in vitro. However, it is
not known if acidosis induced by hemorrhagic shock or infusion of HCl attenuates FVIIa activity in vivo. The purpose
of this study was to determine if acidosis, induced by two methods, affects recombinant FVIIa (rFVIIa) activity in
swine, and if correction of the pH restores rFVIIa activity to normal. Methods: Acidosis was induce in anesthetized
swine in two separate models: 1) HCl infusion (n=10) and 2) hemorrhage/hypoventilation (n=8). Three groups per
model were used: Control (pH7.4), Acidosis (arterial pH7.1) and Acidosis-Corrected (bicarbonate infusion to return
pH from 7.1 to 7.4). Pigs were then injected with rFVIIa (90 μg/kg) or vehicle (saline) at target pH and arterial blood
samples were taken for measurement of coagulation function, including Thromboelastography -TEG, Thrombin Generation,
Activated Clotting Time, Prothrombin Time, activated Partial Thromboplastin Time, Fibrinogen Concentration
and Platelet count before and 5min after injection of rFVIIa. Results: Acidosis led to a hypocoagulation as
measured by almost all coagulation parameters in both models. Furthermore, the change in coagulation function
produced after infusion of rFVIIa was not different between control, acidosis and acidosis-corrected groups for all
coagulation parameters measured. Conclusion: Acidosis associated with hemorrhagic shock or HCl infusion led to a
hypocoagulation that was not corrected with bicarbonate infusion. Furthermore, acidosis did not affect rFVIIa function,
and correction of the acidosis with bicarbonate had no effect on rFVIIa function in these models. This suggests
that in vivo acidosis did not diminish rFVIIa function.
Keywords: Hemorrhage, acidosis, hypoventilation, hypocoagulation, thromboelastography, thrombin generation,
rotational thromboelastogram, fibrinogen, platelets, coagulation parameters, recombinant factor VIIa
Address correspondence to:
Daniel N Darlington
US Army Institute of Surgical Research
Fort Sam Houston, TX 78234, USA.
E-mail: Daniel.darlington@amedd.army.mil
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