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Assessment of coagulopathy, endothelial injury, and inflammation after traumatic brain injury and hemorrhage in a porcine model

Sillesen, Martin MD; Rasmussen, Lars S. MD, PhD, DMsc; Jin, Guang MD PhD; Jepsen, Cecilie H. MD; Imam, Ayesha MD; Hwabejire, John O. MD, MPH; Halaweish, Ihab MD; DeMoya, Marc MD; Velmahos, George MD, PhD; Johansson, Pär I. MD, DMsc, MPA; Alam, Hasan B. MD

Journal of Trauma and Acute Care Surgery: January 2014 - Volume 76 - Issue 1 - p 12–20
doi: 10.1097/TA.0b013e3182aaa675
AAST 2013 Plenary Papers

BACKGROUND Traumatic brain injury (TBI) and hemorrhagic shock (HS) can be associated with coagulopathy and inflammation, but the mechanisms are poorly understood. We hypothesized that a combination of TBI and HS would disturb coagulation, damage the endothelium, and activate inflammatory and complement systems.

METHODS A total of 33 swine were allocated to either TBI + HS (n = 27, TBI and volume-controlled 40% blood loss) or controls (n = 6, anesthesia and instrumentation). TBI + HS animals were left hypotensive (mean arterial pressure, 30–35 mm Hg) for 2 hours. Blood samples were drawn at baseline, 3 minutes and 15 minutes after injury, as well as following 2 hours of hypotension. Markers of coagulation, anticoagulation, endothelial activation/glycocalyx shedding, inflammation, complement, and sympathoadrenal function were measured.

RESULTS The TBI + HS group demonstrated an immediate (3 minutes after injury) activation of coagulation (prothrombin fragment 1 + 2, 289 ng/mL vs. 232 ng/mL, p = 0.03) and complement (C5a, 2.83 ng/mL vs. 2.05 ng/mL, p = 0.05). Shedding of the endothelial glycocalyx (syndecan 1) was evident 15 minutes after injury (851.0 ng/ml vs. 715.5 ng/ml, p = 0.03) while inflammation (tumor necrosis factor α [TNF-α], 81.1 pg/mL vs. 50.8 pg/mL, p = 0.03) and activation of the protein C system (activated protein C, 56.7 ng/mL vs. 26.1 ng/mL, p = 0.01) were evident following the 2-hour hypotension phase.

CONCLUSION The combination of TBI and shock results in an immediate activation of coagulation and complement systems with subsequent endothelial shedding, protein C activation, and inflammation.

From the Division of Trauma, Emergency Surgery and Surgical Critical Care (M.S., C.H.J., A.I., J.O.H., M.D., G.V.), Department of Surgery, Massachusetts GeneralHospital/Harvard Medical School, Boston, Massachusetts; Department of Surgery (G.J., I.H., H.B.A.), University of Michigan, Ann Arbor, Michigan; and Department of Surgery (P.I.J.), University of Texas Medical School, Houston, Texas; and Department of Anesthesia (M.S., L.S.R.), Center of Head and Orthopedics, and Capital Region Blood Bank (C.H.J., P.I.J.), Copenhagen University Hospital, Rigshospitalet, Denmark.

Submitted: July 31, 2013, Revised: August 26, 2013, Accepted: August 29, 2013.

This study was presented at the 72nd annual meeting of the American Association for the Surgery of Trauma, September 18–21, 2013, in San Francisco, California.

Address for reprints: Hasan B. Alam, MD, General Surgery, 2920 Taubman Center, University of Michigan Hospital, 1500 E Medical Center Dr, Ann Arbor, MI 48109; email:

© 2014 Lippincott Williams & Wilkins, Inc.