title: Platelet activation and dysfunction in a large-animal model of traumatic brain injury and hemorrhage.
abstract: BACKGROUND
  Traumatic brain injury (TBI) and hemorrhage are the leading causes of trauma-related mortality. Both TBI and hemorrhage are associated with coagulation disturbances, including platelet dysfunction. We hypothesized that platelet dysfunction could be detected early after injury, and that this dysfunction would be associated with early activation, as measured by circulating levels of platelet activation markers.
  
  
  METHODS
  A total of 33 swine were allocated to TBI and hypotension (n = 27, TBI and volume-controlled 40% blood loss) or controls (n = 6, anesthesia and instrumentation only). Animals in the TBI/Hemorrhage group were left hypotensive, defined as mean arterial pressure of 35 mm Hg, for 2 hours. Blood samples were drawn at baseline and 3 minutes and 15 minutes following injury as well as following 2 hours of shock. Samples were analyzed for platelet aggregation using impedance aggregometry with agonists collagen, arachidonic acid, and adenosine diphosphate (ADP) and thromboelastography (TEG) and circulating levels of platelet activation markers transforming growth factor-β (TGF-β), CD40 ligand, and sP-selectin.
  
  
  RESULTS
  Platelet ADP aggregation was significantly lower in the TBI/Hemorrhage group when compared with the control group 15 minutes following injury (62.4 vs. 80.4 U, p = 0.03) as well as following 2 hours of hypotension (59.9 vs. 73.5 U, p < 0.01). The latter was associated with lower TEG measured clot strength (TEG-MA, 74.1 vs. 79.4 mm, p = 0.05). No difference in collagen or arachidonic acid aggregation was observed. TGF-β levels were significantly higher in the TBI/Hemorrhage group following 2 hours of hypotension (1,764 vs. 1,252 pg/mL, p = 0.01). No differences in CD40 ligand or sP-selectin levels were observed.
  
  
  CONCLUSIONS
  In this combined model of TBI and hemorrhage, a significantly lower ADP-induced platelet aggregation was detected 15 minutes following injury that was further aggravated during the 2-hour shock period. This dysfunction was associated with an increase in platelet activation marker TGF-β.
authors.affiliation: Department of Anesthesia, Center of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Sillesen
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.forename: Lars S
authors.initials: LS
authors.lastname: Rasmussen
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Cecilie H
authors.initials: CH
authors.lastname: Jepsen
authors.forename: Ayehsa M
authors.initials: AM
authors.lastname: Imam
authors.forename: John
authors.initials: J
authors.lastname: Hwabejire
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lu
authors.forename: Michael
authors.initials: M
authors.lastname: Duggan
authors.forename: George
authors.initials: G
authors.lastname: Velmahos
authors.forename: Marc
authors.initials: M
authors.lastname: deMoya
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D020201:Brain Hemorrhage, Traumatic / Q000097:blood*; D001930:Brain Injuries / Q000097:blood*; D023201:CD40 Ligand / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology; D013552:Swine; D013916:Thrombelastography; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D019007:P-Selectin; D016212:Transforming Growth Factor beta; D023201:CD40 Ligand