title: Thrombosomes: a platelet-derived hemostatic agent for control of noncompressible hemorrhage.
abstract: BACKGROUND
  Uncontrolled hemorrhage is responsible for ∼80% of the potentially survivable deaths in combat and over 40% of early mortality in the under 65 age group in the United States. Providing an easily used infusible hemostatic agent to first responders could significantly reduce these fatalities. We report on an infusible lyophilized platelet-derived hemostatic agent stabilized with trehalose and polysucrose prior to and during lyophilization.
  
  
  METHODS
  Characterization included determining the particle population size range, surface marker expression GPIb, GPIIbIIIa, and Annexin V binding. Function was assessed by aggregation, thromboelastography, and thrombin generation. Pharmacokinetics, biodistribution, and immunogenicity established using Indium(111) labeled Thrombosomes in healthy New Zealand white rabbits (NZWRs), efficacy in thrombocytopenic NZWR, and safety in NZWRs, canines, and nonhuman primates.
  
  
  RESULTS
  Thrombosomes retained GPIIbIIIa expression (98.71% ± 0.18 of the rehydrated particles), a reduced expression of GPIb (47.77% ± 6.65), and Annexin V binding (86.05% ± 2.65). Aggregation to all agonists except thrombin in buffer (78.15% ± 2.5) was <50%. Thrombin generation and thromboelastography results demonstrated a concentration gradient that was consistent from lot to lot. There were no observed adverse events in any safety study and blood loss was reduced by >80% in the thrombocytopenic ear bleed model.
  
  
  CONCLUSIONS
  Our in vitro characterization studies in conjunction with preclinical animal safety and efficacy studies demonstrated lot consistency in manufacturing, maintenance of hemostatic functions of Thrombosomes, safety at high dose concentrations, and the potential to provide an effective hemostatic agent at the site of injury.
authors.affiliation: Cellphire Inc., Rockville, Maryland 20882, USA. mfitzpatrick@cellphire.com
authors.forename: G Michael
authors.initials: GM
authors.lastname: Fitzpatrick
authors.forename: Richard
authors.initials: R
authors.lastname: Cliff
authors.forename: Narendra
authors.initials: N
authors.lastname: Tandon
mesh_terms: D000818:Animals; D001458:Bandages; D001792:Blood Platelets / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D005612:Freeze Drying; D006470:Hemorrhage / Q000209:etiology* / Q000628:therapy*; D006489:Hemostatic Techniques; D006801:Humans; D008253:Macaca mulatta; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D017713:Platelet Transfusion / Q000379:methods*; D011817:Rabbits; D013917:Thrombin / Q000378:metabolism; D015599:Trauma Severity Indices; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013917:Thrombin