title: Control of severe intra-abdominal hemorrhage with an infusible platelet-derived hemostatic agent in a nonhuman primate (rhesus macaque) model.
abstract: BACKGROUND
  Hemorrhage remains the leading cause of potentially survivable trauma mortality. Recent reports indicate that injuries sustained in noncompressible anatomic locations (i.e., truncal and junctional) account for 86.5% of hemorrhage-related deaths. Infusible human platelet-derived hemostatic agents (hPDHAs) represent a promising strategy to reduce blood loss from noncompressible injuries. Here, we evaluate the hemostatic efficacy of a lyophilized hPDHA in a rhesus macaque model of severe, uncontrolled hemorrhage.
  
  
  METHODS
  Hemorrhage was induced via laparoscopic 60% left-lobe hepatectomy in anesthetized rhesus macaques (T = 0 minute). Treatment infusion began with an 11-mL bolus (T = 5-6 minutes) of either 5% albumin solution (control; n = 8) or hPDHA (1.2 × 10(10) platelet equivalents, n = 8), followed by 2.8-mL/min 0.9% normal saline at T = 6-20 minutes. Resuscitation continued with normal saline (0.22 mL/kg/min) to a total volume of 20 mL/kg at T = 120 minutes, at which time surgical hemostasis was achieved and percent blood loss quantified. Animals were monitored until T = 480 minutes and then euthanized, and necropsy was performed with emphasis on intravascular and end-organ thrombi. Data are expressed as mean ± SEM; significance, p < 0.05.
  
  
  RESULTS
  Both groups exhibited a ∼70% decrease in mean arterial pressure (MAP) from T = 0-5 minutes. Percent blood loss was 44.2 ± 3.9% in hPDHA animals, and 44.3 ± 3.3% in controls. Survival rates were 4 of 8 for hPDHA animals and 7 of 8 for controls. Regardless of treatment, percent blood loss was greater (p < 0.02) in nonsurviving animals (55 ± 2%, n = 5) compared with surviving animals (42% ± 3%, n = 11). No pathologic intravascular thrombi were observed in either group.
  
  
  CONCLUSIONS
  The isolated administration of hPDHA did not significantly reduce blood loss; however, thrombocytopenia was not present in the model, and clinically, platelets would be administered in combination with plasma. Mortality was not statistically different between groups (p = 0.14) but was related to blood loss. Future studies should consider the use of hPDHA in combination with additional therapeutics (e.g., factors) and a model that incorporates thrombocytopenia or platelet dysfunction.
authors.affiliation: From the Naval Medical Research Unit San Antonio (A.R.M., R.F.C., D.M.F., F.R.S.), US Army Institute of Surgical Research (A.P.C.), and San Antonio Military Medical Center (T.A.M.), JBSA-Fort Sam Houston, San Antonio, Texas; and US Army Medical Research and Material Command (A.E.P.), Fort Detrick, Maryland.
authors.forename: Antoni R
authors.initials: AR
authors.lastname: Macko
authors.forename: Randy F
authors.initials: RF
authors.lastname: Crossland
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Cap
authors.forename: Darren M
authors.initials: DM
authors.lastname: Fryer
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mitchell
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pusateri
authors.forename: Forest R
authors.initials: FR
authors.lastname: Sheppard
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001780:Blood Coagulation Tests; D001784:Blood Gas Analysis; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005612:Freeze Drying; D006339:Heart Rate / Q000502:physiology; D006465:Hemoperitoneum / Q000628:therapy*; D006489:Hemostatic Techniques; D006490:Hemostatics / Q000008:administration & dosage / Q000494:pharmacology*; D006498:Hepatectomy; D008253:Macaca mulatta; D008297:Male; D015996:Survival Rate
chemical_list: D016207:Cytokines; D006490:Hemostatics