P. J. Lawson1, H. B. Moore1,2, G. R. Stettler1,2, A. L. Slaughter1,2, A. W. Bacon1,2, M. Fragoso1,2, A. Banerjee1, E. E. Moore1,2 1University Of Colorado Denver,Aurora, CO, USA 2Denver Health Medical Center,Aurora, CO, USA
Introduction:
Thrombelastography (TEG) has been used increasingly to characterize the coagulation changes associated with traumatic injury and hemorrhagic shock. However, animal models developed to investigate trauma induced coagulopathy (TIC) have failed to produce objective excessive bleeding. In patients activated TEGs (rapid and kaolin) are less sensitive in detecting hypercoaguable states following injury compared to a non-activated (native) TEG. We hypothesize that a native TEG will demonstrate marked differences in humans compared to these experimental models, which explains the difficulties in reproducing a clinically relevant coagulopathy in animal models.
Methods:
Whole blood was collected from 134 healthy human volunteers, 25 swine and 64 Sprague Dawley rats prior to experimentation. Citrated Native TEG’s were run on each whole blood sample within 2 hours of blood draw. The R-Time(min), Angle(degrees), MA(mm), and LY30(%) were analyzed and contrasted between species with data represented as the median and 25th to 75th quartile range. Difference between species was conducted with a Kruskall Wallis test with alpha adjusted with a Bonferroni correction for multiple comparison (alpha = 0.016).
Results:
R-Time (clot initiation) was 17.9 min (15.0-21.1) for humans, 5.7 (4.9-8.8) for pigs, and 5.2 (4.4-6) for rodents. Humans had longer R-Times than both pigs (p<0.0001) and rats (p<0.0001); pigs were not different from rats. Angle (fibrin cross-linking) was 28.0 degrees (21.4-40.3) for humans, 71.7 (64.3-75.6) for pigs, and 61.8 (56.8-66.7) for rats. Humans had reduced Angle than both pigs (p<0.0001) and rats (p<0.0001); pigs were not different from rats. MA (clot strength) was 51.5 mm (47.4-55.0) for humans, 72.5 (70.4-75.5) for pigs, and 66.5 (56.5-68.6) for rats. Humans had reduced MA than both pigs (p<0.0001) and rats (p<0.0001); pigs were not different from rats. LY30 (fibrinolysis) was 1.2 % (0.6-2.2) for humans, 3.3 (1.9-4.3) for pigs, and 0.5 (0.1-1.2) for rats. Humans had a lesser LY30 than pigs (p=0.0006) and a greater LY30 than rats (p=0.0005), and pigs had a greater LY30 than rats (p<0.0001).
Conclusion:
Humans, swine, and rodents have distinctly different coagulation profiles when evaluated by native TEG. Animals are hypercoaguable with rapid clotting times and clots strengths nearly 50% stronger than humans. These coagulation differences indicate the limitations of previous models of TIC in producing coagulation abnormalities associated with increased bleeding. The inherent hypercoaguable baseline tendencies of these animals may result in subclinical biochemical changes that are not detected by conventional TEG and should be taken into consideration when extrapolated to clinical medicine.
