Clinical and mechanistic drivers of acute traumatic coagulopathy

Mitchell Jay Cohen; Matt Kutcher; Britt Redick; Mary Nelson; Mariah Call; 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

doi:10.1097/TA.0b013e31828fa43d

Clinical and mechanistic drivers of acute traumatic coagulopathy

Mitchell Jay Cohen^*, Matt Kutcher, Britt Redick, Mary Nelson, Mariah Call, 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

180 Scopus citations

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 language	English
Pages (from-to)	S40-S47
Journal	Journal of Trauma and Acute Care Surgery
Volume	75
Issue number	1 SUPPL1
DOIs	https://doi.org/10.1097/TA.0b013e31828fa43d
State	Published - 2013
Externally published	Yes

Keywords

Bleeding
Coagulation
Injury
PROMMTT
Trauma

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10.1097/TA.0b013e31828fa43d

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Cohen, M. J., Kutcher, M., Redick, B., Nelson, M., Call, M., Knudson, M., Schreiber, M. A., Bulger, E. M., Muskat, P., Alarcon, L. H., Myers, J. G., Rahbar, M. H., Brasel, K. J., Phelan, H. A., Del Junco, D. J., Fox, E. E., Wade, C. E., Holcomb, J. B., Cotton, B. A., & Matijevic, N. (2013). Clinical and mechanistic drivers of acute traumatic coagulopathy. Journal of Trauma and Acute Care Surgery, 75(1 SUPPL1), S40-S47. https://doi.org/10.1097/TA.0b013e31828fa43d

@article{9226bf908a4641f6a2c2de9c07fa90cf,

title = "Clinical and mechanistic drivers of acute traumatic coagulopathy",

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 Schreiber, {Martin A.} and Bulger, {Eileen M.} and Peter Muskat and Alarcon, {Louis H.} and Myers, {John G.} and Rahbar, {Mohammad H.} and Brasel, {Karen J.} 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",

year = "2013",

doi = "10.1097/TA.0b013e31828fa43d",

language = "English",

volume = "75",

pages = "S40--S47",

journal = "Journal of Trauma and Acute Care Surgery",

issn = "2163-0755",

publisher = "LWW",

number = "1 SUPPL1",

}

Cohen, MJ, Kutcher, M, Redick, B, Nelson, M, Call, M, Knudson, M, Schreiber, MA, Bulger, EM, Muskat, P, Alarcon, LH, Myers, JG, Rahbar, MH, Brasel, KJ, 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, pp. S40-S47. https://doi.org/10.1097/TA.0b013e31828fa43d

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 A.

AU - Bulger, Eileen M.

AU - Muskat, Peter

AU - Alarcon, Louis H.

AU - Myers, John G.

AU - Rahbar, Mohammad H.

AU - Brasel, Karen J.

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

UR - http://www.scopus.com/inward/record.url?scp=84880405233&partnerID=8YFLogxK

U2 - 10.1097/TA.0b013e31828fa43d

DO - 10.1097/TA.0b013e31828fa43d

M3 - Article

C2 - 23778510

AN - SCOPUS:84880405233

SN - 2163-0755

VL - 75

SP - S40-S47

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

IS - 1 SUPPL1

ER -

Clinical and mechanistic drivers of acute traumatic coagulopathy

Abstract

Keywords

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