J. R. Coleman1, S. Butenas2, J. M. Samuels1, M. G. Bartley1, N. G. Vigneshwar1, J. T. Nelson4,5, J. J. Ryon3, A. Olson2, A. Sauaia1, A. Banerjee1, C. C. Silliman5, E. E. Moore2,3 1University of Colorado-Denver,Surgery,Aurora, CO, USA 2University of Vermont,Biochemistry,Burlington, VT, USA 3Denver Health,Surgery,Denver, CO, USA 4Rosalind Franklin University of Medicine and Science,Chicago Medical School,North Chicago, IL, USA 5Children’s Hospital Colorado,Hematology,Aurora, CO, USA
Introduction:
Thrombin is a serine protease responsible for conversion of soluble fibrinogen into insoluble fibrin and is the end-point of the coagulation cascade. As such, measurement of thrombin generation (TG) offers an important description of the coagulation status of a patient. Historically, plasma TG has been used to describe coagulopathy of trauma, but the description of whole blood (WB) TG is lacking in the literature. This study aims to compare plasma and WB TG and then to examine clinical correlations with WB TG in trauma patients. We hypothesize that 1) WB TG does not correlate with plasma TG and 2) severely injured trauma patients demonstrate a unique WB TG profile.
Methods:
To compare plasma and whole blood TG, blood was collected from healthy volunteers. WB TG was performed using a prototype point-of-care WB TG device (Near Patient Testing Thrombin Generation; NPT-TG) and the remaining blood was spun down to perform platelet-poor plasma TG with a BioTek plate reader (CAT analogue). To examine clinical correlatives in trauma patients, initial blood was collected as part of a prospective study of trauma activation patients before arrival or upon presentation to a large, urban, level-1 trauma center. WB TG was performed within one hour of venipuncture. TG yields the following measurements: lag time, peak thrombin, time to peak thrombin, maximum rate (or velocity index) and endogenous thrombin potential (ETP). Correlation between plasma and WB TG were compared using Pearson’s correlation. WB TG measurements were compared between severely injured patients (new injury severity score [NISS] > 15) and non-severely injured patients (NISS ≤ 15) with the Mann-Whitney test.
Results:
Overall, 10 healthy volunteers were included in this study. There was poor correlation between the plasma and WB TG, with plasma reflecting a more prolonged time to peak thrombin, higher rate of TG and higher ETP (R2 values ranged from 0.07 to 0.47, p values 0.17 to 0.83). Additionally, 49 trauma patients were included in this study. The average age was 37.6 years and the majority (76%) were male. 59% presented after blunt trauma and the median NISS was 17. On examining WB TG, severely injury patients (NISS>15) had a prolonged lag time (4.3 min versus 3.0 min, p=0.03), depressed peak thrombin (123.7 nM versus 135.6 nM, p=0.02) and slower rate of thrombin generation (37.2 nM/min versus 54.2 nM/min, p=0.02) than less severely injured patients. They also demonstrated a trend towards prolonged time to peak thrombin (7.8 min versus 5.6 min, p=0.08) and decreased ETP (798.7 versus 831.8 nM/L x min, p=0.27).
Conclusion:
Plasma and WB TG do not correlate, supporting the cellular-based understanding of coagulation. These results challenge the previous assumption that severely injured trauma patients are believed to be initially hypercoagulable, leading to consumptive coagulopathy and hypocoagulopathy. These data instead describe an initial hypocoagulable profile which is pronounced after severe injury and characterized by prolonged time to thrombin formation, decreased maximum thrombin and slow rate of thrombin generation.