Clinical and mechanistic drivers of acute traumatic coagulopathy

Mitchell Jay Cohen, Matt Kutcher, Britt Redick, Mary Nelson, Mariah Call, M Margaret Knudson, Martin A Schreiber, Eileen M Bulger, Peter Muskat, Louis H Alarcon, John G Myers, Mohammad H Rahbar, Karen J Brasel, Herb A Phelan, Deborah J del Junco, Erin E Fox, Charles E Wade, John B Holcomb, Bryan A Cotton, Nena Matijevic, PROMMTT Study Group, Mohammad H Rahbar, John B Holcomb, Erin E Fox, Deborah J del Junco, Bryan A Cotton, Charles E Wade, Jiajie Zhang, Nena Matijevic, Yu Bai, Weiwei Wang, Jeanette Podbielski, Sarah J Duran, Ruby Benjamin-Garner, Robert J Reynolds, Xuan Zhang, Aisha Dickerson, Elizabeth S Camp, John B Holcomb, Bryan A Cotton, Marily Elopre, Quinton M Hatch, Michelle Scerbo, Zerremi Caga-Anan, Christopher E White, Kimberly L Franzen, Elsa C Coates, Karen J Brasel, Pamela Walsh, Martin A Schreiber, Samantha J Underwood, Jodie Curren, Mitchell J Cohen, M Margaret Knudson, Mary Nelson, Mariah S Call, Peter Muskat, Jay A Johannigman, Bryce R H Robinson, Richard Branson, Dina Gomaa, Cendi Dahl, Louis H Alarcon, Andrew B Peitzman, Stacy D Stull, Mitch Kampmeyer, Barbara J Early, Helen L Shnol, Samuel J Zolin, Sarah B Sears, John G Myers, Ronald M Stewart, Rick L Sambucini, Marianne Gildea, Mark DeRosa, Rachelle Jonas, Janet McCarthy, Herbert A Phelan, Joseph P Minei, Elizabeth Carroll, Eileen M Bulger, Patricia Klotz, Keir J Warner, Mitchell Jay Cohen, Matt Kutcher, Britt Redick, Mary Nelson, Mariah Call, M Margaret Knudson, Martin A Schreiber, Eileen M Bulger, Peter Muskat, Louis H Alarcon, John G Myers, Mohammad H Rahbar, Karen J Brasel, Herb A Phelan, Deborah J del Junco, Erin E Fox, Charles E Wade, John B Holcomb, Bryan A Cotton, Nena Matijevic, PROMMTT Study Group, Mohammad H Rahbar, John B Holcomb, Erin E Fox, Deborah J del Junco, Bryan A Cotton, Charles E Wade, Jiajie Zhang, Nena Matijevic, Yu Bai, Weiwei Wang, Jeanette Podbielski, Sarah J Duran, Ruby Benjamin-Garner, Robert J Reynolds, Xuan Zhang, Aisha Dickerson, Elizabeth S Camp, John B Holcomb, Bryan A Cotton, Marily Elopre, Quinton M Hatch, Michelle Scerbo, Zerremi Caga-Anan, Christopher E White, Kimberly L Franzen, Elsa C Coates, Karen J Brasel, Pamela Walsh, Martin A Schreiber, Samantha J Underwood, Jodie Curren, Mitchell J Cohen, M Margaret Knudson, Mary Nelson, Mariah S Call, Peter Muskat, Jay A Johannigman, Bryce R H Robinson, Richard Branson, Dina Gomaa, Cendi Dahl, Louis H Alarcon, Andrew B Peitzman, Stacy D Stull, Mitch Kampmeyer, Barbara J Early, Helen L Shnol, Samuel J Zolin, Sarah B Sears, John G Myers, Ronald M Stewart, Rick L Sambucini, Marianne Gildea, Mark DeRosa, Rachelle Jonas, Janet McCarthy, Herbert A Phelan, Joseph P Minei, Elizabeth Carroll, Eileen M Bulger, Patricia Klotz, Keir J Warner

Abstract

Background: Acute traumatic coagulopathy (ATC) occurs after severe injury and shock and is associated with increased bleeding, morbidity, and mortality. The effects of ATC and hemostatic resuscitation on outcome are not well-explored. The PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study provided a unique opportunity to characterize coagulation and the effects of resuscitation on ATC after severe trauma.

Methods: Blood samples were collected upon arrival on a subset of PROMMTT patients. Plasma clotting factor levels were prospectively assayed for coagulation factors. These data were analyzed with comprehensive PROMMTT clinical data.

Results: There were 1,198 patients with laboratory results, of whom 41.6% were coagulopathic. Using international normalized ratio of 1.3 or greater, 41.6% of patients (448) were coagulopathic, while 20.5% (214) were coagulopathic using partial thromboplastin time of 35 or greater. Coagulopathy was primarily associated with a combination of an Injury Severity Score (ISS) of greater than 15 and a base deficit (BD) of less than -6 (p < 0.05). Regression modeling for international normalized ratio-based coagulopathy shows that prehospital crystalloid (odds ratio [OR], 1.05), ISS (OR, 1.03), Glasgow Coma Scale (GCS) score (OR, 0.93), heart rate (OR, 1.08), systolic blood pressure (OR, 0.96), BD (OR, 0.92), and temperature (OR, 0.84) were significant predictors of coagulopathy (all p < 0.03). A subset of 165 patients had blood samples collected and coagulation factor analysis performed. Elevated ISS and BD were associated with elevation of aPC and depletion of factors (all p < 0.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p < 0.04). Similar results were found for partial thromboplastin time-defined coagulopathy.

Conclusion: ATC is associated with the depletion of factors I, II, V, VII, VIII, IX, and X and is driven by the activation of the protein C system. These data provide additional mechanistic understanding of the drivers of coagulation abnormalities after injury. Further understanding of the drivers of ATC and the effects of resuscitation can guide factor-guided resuscitation and correction of coagulopathy after injury.