title: Fresh frozen plasma resuscitation attenuates platelet dysfunction compared with normal saline in a large animal model of multisystem trauma.
abstract: BACKGROUND
  Platelet dysfunction following trauma has been identified as an independent predictor of mortality. We hypothesized that fresh frozen plasma (FFP) resuscitation would attenuate platelet dysfunction compared with 0.9% normal saline (NS).
  
  
  METHODS
  Twelve swine were subjected to multisystem trauma (traumatic brain injury, liver injury, rib fracture, and soft tissue injury) with hemorrhagic shock (40% of estimated blood volume). Animals were left in shock (mean arterial pressure, 30-35 mm Hg) for 2 hours followed by resuscitation with three times shed volume NS (n = 6) or one times volume FFP (n = 6) and monitored for 6 hours. Platelet function was assessed by adenosine diphosphate (ADP)-induced platelet aggregation at baseline, after 2 hours of shock following resuscitation, and 6 hours after resuscitation. Fibrinogen levels and markers of platelet activation (transforming growth factor β [TGF-β], sP-Selectin, and CD40L) as well as endothelial injury (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]) were also assayed. Thromboelastography was used to measure clotting activity.
  
  
  RESULTS
  ADP-induced platelet aggregation was significantly higher in the FFP group (46.3 U vs. 25.5 U, p < 0.01) following resuscitation. This was associated with higher fibrinogen levels (202 mg/dL vs. 80 mg/dL, p < 0.01) but lower endothelial activation (VCAM-1, 1.25 ng/mL vs. 3.87 ng/mL, p = 0.05). Other markers did not differ.After 6 hours of observation, ADP-induced platelet aggregation remained higher in the FFP group (53.8 U vs. 37.0 U, p = 0.03) as was fibrinogen levels (229 mg/dL vs. 153 mg/dL, p < 0.01). Endothelial activation was lower (ICAM-1, 21.0 ng/mL vs. 24.4 ng/mL, p = 0.05), whereas TGF-β levels were higher (2,138 pg/mL vs. 1,802 pg/mL, p = 0.03) in the FFP group. Other markers did not differ. Thromboelastography revealed increased clot strength in the FFP group at both postresuscitation time points.
  
  
  CONCLUSIONS
  Resuscitation with FFP resulted in an immediate and sustained improvement in platelet function and clot strength compared with high-volume NS resuscitation. This was associated with an increase in fibrinogen levels and an attenuation of endothelial activation.
authors.affiliation: From the Division of Trauma, Emergency Surgery and Surgical Critical Care (M.S., C.H.J., A.I., J.O.H., D.D., M.Du., M.De., G.C.V.), Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts; Department of Anesthesia (M.S., L.S.R.), Center of Head and Orthopedics, and Capital Region Blood Bank (P.I.J., C.H.J.), Copenhagen University Hospital, Rigshospitalet, Denmark; Department of Surgery (P.I.J.), University of Texas Medical School at Houston, Texas; and Department of Surgery (G.J., H.B.A.), University of Michigan, Ann Arbor, Michigan.
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: Ayesha
authors.initials: A
authors.lastname: Imam
authors.forename: John O
authors.initials: JO
authors.lastname: Hwabejire
authors.forename: Danielle
authors.initials: D
authors.lastname: Deperalta
authors.forename: Michael
authors.initials: M
authors.lastname: Duggan
authors.forename: Marc
authors.initials: M
authors.lastname: DeMoya
authors.forename: George C
authors.initials: GC
authors.lastname: Velmahos
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D009104:Multiple Trauma / Q000628:therapy*; D010949:Plasma; D015539:Platelet Activation; D012151:Resuscitation / Q000379:methods*; D012965:Sodium Chloride / Q000494:pharmacology*; D013552:Swine
chemical_list: D012965:Sodium Chloride