Clinical and mechanistic drivers of acute traumatic coagulopathy

Mitchell Jay Cohen, Matt Kutcher, Britt Redick, Mary Nelson, Mariah Call, Margaret Knudson, Martin Schreiber, Eileen M. Bulger, Peter Muskat, Louis H. Alarcon, John G. Myers, Mohammad H. Rahbar, Karen Brasel, Herb A. Phelan, Deborah J. Del Junco, Erin E. Fox, Charles E. Wade, John B. Holcomb, Bryan A. Cotton, Nena Matijevic

    Research output: Contribution to journalArticle

    99 Citations (Scopus)

    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 j6 (p G 0.05). Regression modeling for international normalized ratioYbased 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 G 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 G 0.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p G 0.04). Similar results were found for partial thromboplastin timeYdefined 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.

    Original languageEnglish (US)
    JournalJournal of Trauma and Acute Care Surgery
    Volume75
    Issue number1 SUPPL1
    DOIs
    StatePublished - 2013

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    Odds Ratio
    Resuscitation
    Wounds and Injuries
    Injury Severity Score
    Blood Coagulation Factors
    Fibrinogen
    Blood Pressure
    Glasgow Coma Scale
    International Normalized Ratio
    Partial Thromboplastin Time
    Thromboplastin
    Hemostatics
    Protein C
    Statistical Factor Analysis
    Shock
    Heart Rate
    Hemorrhage
    Morbidity
    Temperature
    Mortality

    Keywords

    • Bleeding
    • Coagulation
    • Injury
    • PROMMTT
    • Trauma

    ASJC Scopus subject areas

    • Critical Care and Intensive Care Medicine
    • Surgery

    Cite this

    Cohen, M. J., Kutcher, M., Redick, B., Nelson, M., Call, M., Knudson, M., ... Matijevic, N. (2013). Clinical and mechanistic drivers of acute traumatic coagulopathy. Journal of Trauma and Acute Care Surgery, 75(1 SUPPL1). https://doi.org/10.1097/TA.0b013e31828fa43d

    Clinical and mechanistic drivers of acute traumatic coagulopathy. / Cohen, Mitchell Jay; Kutcher, Matt; Redick, Britt; Nelson, Mary; Call, Mariah; Knudson, Margaret; Schreiber, Martin; Bulger, Eileen M.; Muskat, Peter; Alarcon, Louis H.; Myers, John G.; Rahbar, Mohammad H.; Brasel, Karen; Phelan, Herb A.; Del Junco, Deborah J.; Fox, Erin E.; Wade, Charles E.; Holcomb, John B.; Cotton, Bryan A.; Matijevic, Nena.

    In: Journal of Trauma and Acute Care Surgery, Vol. 75, No. 1 SUPPL1, 2013.

    Research output: Contribution to journalArticle

    Cohen, MJ, Kutcher, M, Redick, B, Nelson, M, Call, M, Knudson, M, Schreiber, M, Bulger, EM, Muskat, P, Alarcon, LH, Myers, JG, Rahbar, MH, Brasel, K, Phelan, HA, Del Junco, DJ, Fox, EE, Wade, CE, Holcomb, JB, Cotton, BA & Matijevic, N 2013, 'Clinical and mechanistic drivers of acute traumatic coagulopathy', Journal of Trauma and Acute Care Surgery, vol. 75, no. 1 SUPPL1. https://doi.org/10.1097/TA.0b013e31828fa43d
    Cohen, Mitchell Jay ; Kutcher, Matt ; Redick, Britt ; Nelson, Mary ; Call, Mariah ; Knudson, Margaret ; Schreiber, Martin ; Bulger, Eileen M. ; Muskat, Peter ; Alarcon, Louis H. ; Myers, John G. ; Rahbar, Mohammad H. ; Brasel, Karen ; Phelan, Herb A. ; Del Junco, Deborah J. ; Fox, Erin E. ; Wade, Charles E. ; Holcomb, John B. ; Cotton, Bryan A. ; Matijevic, Nena. / Clinical and mechanistic drivers of acute traumatic coagulopathy. In: Journal of Trauma and Acute Care Surgery. 2013 ; Vol. 75, No. 1 SUPPL1.
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    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 j6 (p G 0.05). Regression modeling for international normalized ratioYbased 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 G 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 G 0.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p G 0.04). Similar results were found for partial thromboplastin timeYdefined 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.",
    keywords = "Bleeding, Coagulation, Injury, PROMMTT, Trauma",
    author = "Cohen, {Mitchell Jay} and Matt Kutcher and Britt Redick and Mary Nelson and Mariah Call and Margaret Knudson and Martin Schreiber and Bulger, {Eileen M.} and Peter Muskat and Alarcon, {Louis H.} and Myers, {John G.} and Rahbar, {Mohammad H.} and Karen Brasel and Phelan, {Herb A.} and {Del Junco}, {Deborah J.} and Fox, {Erin E.} and Wade, {Charles E.} and Holcomb, {John B.} and Cotton, {Bryan A.} and Nena Matijevic",
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    doi = "10.1097/TA.0b013e31828fa43d",
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    TY - JOUR

    T1 - Clinical and mechanistic drivers of acute traumatic coagulopathy

    AU - Cohen, Mitchell Jay

    AU - Kutcher, Matt

    AU - Redick, Britt

    AU - Nelson, Mary

    AU - Call, Mariah

    AU - Knudson, Margaret

    AU - Schreiber, Martin

    AU - Bulger, Eileen M.

    AU - Muskat, Peter

    AU - Alarcon, Louis H.

    AU - Myers, John G.

    AU - Rahbar, Mohammad H.

    AU - Brasel, Karen

    AU - Phelan, Herb A.

    AU - Del Junco, Deborah J.

    AU - Fox, Erin E.

    AU - Wade, Charles E.

    AU - Holcomb, John B.

    AU - Cotton, Bryan A.

    AU - Matijevic, Nena

    PY - 2013

    Y1 - 2013

    N2 - 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 j6 (p G 0.05). Regression modeling for international normalized ratioYbased 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 G 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 G 0.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p G 0.04). Similar results were found for partial thromboplastin timeYdefined 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.

    AB - 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 j6 (p G 0.05). Regression modeling for international normalized ratioYbased 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 G 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 G 0.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p G 0.04). Similar results were found for partial thromboplastin timeYdefined 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.

    KW - Bleeding

    KW - Coagulation

    KW - Injury

    KW - PROMMTT

    KW - Trauma

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