This work was supported by generous funding from US Defense Advanced Projects Agency (Contract #W911NF-07-C-0052), US Army Medical Research & Materiel Command (Contract #W81XWH-11-1-0045), and Oregon Freeze Dry, Albany, OR.
Thrombosomes: a platelet-derived hemostatic agent for control of noncompressible hemorrhage
Article first published online: 10 JAN 2013
© 2013 American Association of Blood Banks
Special Issue: The THOR Network 2012 Remote Damage Control Resuscitation Symposium
Volume 53, Issue Supplement S1, pages 100S–106S, January 2013
How to Cite
Fitzpatrick, G. M., Cliff, R. and Tandon, N. (2013), Thrombosomes: a platelet-derived hemostatic agent for control of noncompressible hemorrhage. Transfusion, 53: 100S–106S. doi: 10.1111/trf.12043
- Issue published online: 10 JAN 2013
- Article first published online: 10 JAN 2013
- US Defense Advanced Projects Agency. Grant Number: Contract #W911NF-07-C-0052
- US Army Medical Research & Materiel Command. Grant Number: Contract #W81XWH-11-1-0045
- Oregon Freeze Dry, Albany, OR
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.
Study Design and 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 Indium111 labeled Thrombosomes in healthy New Zealand white rabbits (NZWRs), efficacy in thrombocytopenic NZWR, and safety in NZWRs, canines, and nonhuman primates.
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.
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.