title: Nonhuman primate model of polytraumatic hemorrhagic shock recapitulates early platelet dysfunction observed following severe injury in humans.
abstract: Platelet dysfunction has been described as an early component of trauma-induced coagulopathy. The platelet component of trauma-induced coagulopathy remains to be fully elucidated and translatable animal models are required to facilitate mechanistic investigations. We sought to determine if the early platelet dysfunction described in trauma patients could be recapitulated in a nonhuman primate model of polytraumatic hemorrhagic shock.
  
  
  
  Twenty-four male rhesus macaques weighting 7 to 14 kg were subjected to 60 minutes (min) of severe pressure-targeted controlled hemorrhagic shock (HS) with and without other injuries. After 60 min, resuscitation with 0.9% NaCl and whole blood was initiated. Platelet counts and platelet aggregation assays were performed at baseline (BSLN), end of shock (EOS; T = 60 min), end of resuscitation (EOR; T = 180 min), and T = 360 min on overall cohort. Results are reported as mean ± standard deviation (SD) or median (interquartile range). Statistical analysis was conducted using Spearmen correlation, one-way analysis of variance, two-way repeated-measures analysis of variance, paired t-test or Wilcoxon nonparametric test, with p < 0.05 considered significant.
  
  
  
  Platelet count in all injury cohorts decreased over time, but no animals developed thrombocytopenia. Correlations were observed between platelet aggregation and platelet count for all agonists: adenosine diphosphate, thrombin recognition-activating peptide-6, collagen, and arachidonic acid. Overall, compared to BSLN, platelet aggregation decreased for all agonist at EOS, EOR, and T = 360 min. When normalized to platelet count, platelet aggregation in response to agonist thrombin recognition-activating peptide-6 demonstrated no change from BSLN at subsequent time points. Aggregation to adenosine diphosphate was significantly less at EOR but not EOS or T = 360 min compared to BSLN. Platelet aggregation to collagen and arachidonic acid was not significantly different at EOS compared to BSLN but was significantly less at EOR and T = 360 min.
  
  
  
  Nonhuman primates manifest early platelet dysfunction in response to polytraumatic hemorrhagic shock, consistent with that reported in severely injured human patients. Nonhuman primate models potentially are translationally valuable for understanding the mechanisms and pathophysiology of trauma-induced platelet dysfunction.
authors.affiliation: From the Naval Medical Research Unit San Antonio (L.J.S., J.J.G., F.R.S.), JBSA-Fort Sam Houston, Texas; Department of Surgery (H.B.M., E.E.M.), Denver Health Medical Center, Denver, Colorado; University of Colorado Denver (H.B.M., E.E.M.), Aurora, Colorado; and US Army Institute of Surgical Research (A.P.C.), JBSA-Fort Sam Houston, Texas.
authors.forename: Leasha J
authors.initials: LJ
authors.lastname: Schaub
authors.forename: Hunter B
authors.initials: HB
authors.lastname: Moore
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cap
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Glaser
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Forest R
authors.initials: FR
authors.lastname: Sheppard
mesh_terms: D000818:Animals; D001778:Blood Coagulation Disorders / Q000503:physiopathology*; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000502:physiology*; D004195:Disease Models, Animal; D008253:Macaca mulatta; D008297:Male; D009104:Multiple Trauma / Q000503:physiopathology*; D010976:Platelet Count; D010979:Platelet Function Tests; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000503:physiopathology*