Development and Testing of Freeze-Dried Plasma for the Treatment of Trauma-Associated Coagulopathy

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Abstract
Trauma-induced coagulopathy is associated with an extremely high mortality. We have recently shown that survival can be improved by correction of coagulopathy through early, aggressive infusion of Fresh Frozen Plasma (FFP). However, FFP is a perishable product, and its use is impractical in challenging environments such as a battlefield. Development of shelf-stable, easy to use, low volume, lyophilized, Freeze-Dried Plasma (FDP) can overcome the logistical limitations. We hereby report the development and testing of such a product. Plasma separated from fresh porcine blood (n = 10) was either stored as FFP, or lyophilized to produce the FDP. For in vitro testing, the FDP was rehydrated with distilled water and the pH, temperature, and osmolarity were adjusted to match the thawed FFP. Laboratory analysis included measurements of prothrombin time (PT), partial thromboplastin time, fibrinogen levels, and clotting factors II, VII, and IX. To test in vivo efficacy, swine were subjected to multiple injuries (femur fracture and grade V liver injury) and severe hemorrhagic shock (60% blood loss associated with "lethal triad" of coagulopathy, acidosis, and hypothermia), and resuscitated with FFP or FDP (n = 6/group; plasma volumes equal to the volume of shed blood). No treatment, and resuscitation with fresh whole blood served as the control groups (n = 6/group). Coagulation profiles (thromboelastography, PT, partial thromboplastin time, international normalized ratio, fibrinogen) were measured serially during the experiment, and for 4 hours posttreatment. In vitro analysis revealed no differences in the coagulation profiles of FFP and FDP. The lyophilization process did not decrease the activity levels of the measured clotting factors. In the swine model, multiple injuries and hemorrhagic shock caused a 50% to 70% increase in PT (p = 0.03), and infusion of FDP and FFP were equally effective in correcting the coagulopathy. Plasma can be lyophilized and freeze-dried to create a logistically superior product without compromising its hemostatic properties. This product may be suitable for use in austere environments, such as a battlefield, for the treatment of trauma-associated coagulopathy.