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Accession Number:
ADA571614
Title:
Acidosis and Correction of Acidosis Does Not Affect rFVIIa Function in Swine
Descriptive Note:
Journal article
Corporate Author:
ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX
Report Date:
2012-12-15
Pagination or Media Count:
15.0
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 n10 and 2 hemorrhagehypoventilation n8. 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 micro gkg 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.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
