Translational Applications to Acute Traumatic Coagulopathy: Understanding the Biology of Coagulation and Inflammation After Injury

Uncontrolled hemorrhage is the primary cause of potentially preventable death in civilian injuries and combat casualties, and derangements of the coagulation system complicate almost all cases of active bleeding and massive transfusion. These patients die because we do not yet understand the causes of these specific alterations, we cannot accurately and rapidly diagnose them, and we cannot supply targeted therapy quickly enough to effect outcome. Current best practice in trauma care involves the blind provision of large amounts of intravenous blood-derived clotting factor replacement for patients with hemorrhagic shock. Our group and others have recently identified a biochemically distinct acute traumatic coagulopathy that occurs nearly immediately after injury, and is associated with increased morbidity (bleeding, infection, and organ failure), and a nearly 4-fold increase in mortality. Further recent work has identified that this is likely mediated by activation of the protein C system, offering a more complete understanding of the perturbations in coagulation after trauma and the hope of a specific target for therapy. Despite this new insight into acute traumatic coagulopathy, the coagulation milieu after injury remains woefully understudied. Because of this, the Cohen lab has undertaken a multi-faceted, translational investigation of coagulation after trauma and its implications for later immune dysregulation and further morbidity.

Recent Publications

Bir N, Lafargue M, Howard M, Goolaerts A, Roux J, Carles M, Cohen MJ, Iles KE, Fernández JA, Griffin JH, Pittet JF
Cytoprotective-selective activated protein C attenuates Pseudomonas aeruginosa-induced lung injury in mice.
American journal of respiratory cell and molecular biology, Sep-01-2011; 453: 632-41.  Epub 2011 Jan 21.
Calfee CS, Matthay MA, Eisner MD, Benowitz N, Call M, Pittet JF, Cohen MJ
Active and passive cigarette smoking and acute lung injury after severe blunt trauma.
American journal of respiratory and critical care medicine, Jun-15-2011; 18312: 1660-5.  Epub 2011 Mar 18.
Cohen MJ, Serkova NJ, Wiener-Kronish J, Pittet JF, Niemann CU
1H-NMR-based metabolic signatures of clinical outcomes in trauma patients--beyond lactate and base deficit.
The Journal of trauma, Jul-01-2010; 691: 31-40.
Cohen MJ, Carles M, Brohi K, Calfee CS, Rahn P, Call MS, Chesebro BB, West MA, Pittet JF
Early release of soluble receptor for advanced glycation endproducts after severe trauma in humans.
The Journal of trauma, Jun-01-2010; 686: 1273-8.
Cohen MJ, Grossman AD, Morabito D, Knudson MM, Butte AJ, Manley GT
Identification of complex metabolic states in critically injured patients using bioinformatic cluster analysis.
Critical care (London, England), 141: R10.  Epub 2010 Feb 2.
Chesebro BB, Rahn P, Carles M, Esmon CT, Xu J, Brohi K, Frith D, Pittet JF, Cohen MJ
Increase in activated protein C mediates acute traumatic coagulopathy in mice.
Shock (Augusta, Ga.), Dec-01-2009; 326: 659-65.
Cohen MJ, Bir N, Rahn P, Dotson R, Brohi K, Chesebro BB, Mackersie R, Carles M, Wiener-Kronish J, Pittet JF
Protein C depletion early after trauma increases the risk of ventilator-associated pneumonia.
The Journal of trauma, Dec-01-2009; 676: 1176-81.
Cohen MJ, Brohi K, Calfee CS, Rahn P, Chesebro BB, Christiaans SC, Carles M, Howard M, Pittet JF
Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion.
Critical care (London, England), 136: R174.  Epub 2009 Nov 4.
Ganter MT, Cohen MJ, Brohi K, Chesebro BB, Staudenmayer KL, Rahn P, Christiaans SC, Bir ND, Pittet JF
Angiopoietin-2, marker and mediator of endothelial activation with prognostic significance early after trauma?.
Annals of surgery, Feb-01-2008; 2472: 320-6.
Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet JF
Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway?.
Annals of surgery, May-01-2007; 2455: 812-8.
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