Development and testing of low-volume hyperoncotic, hyperosmotic spray-dried plasma for the treatment of trauma-associated coagulopathy

Abstract

Background: Trauma-associated coagulopathy carries an extremely high mortality. Fresh-frozen plasma (FFP) is the mainstay of treatment; however, its availability in the battlefield is limited. We have already shown that lyophilized, freeze-dried plasma (FDP) reconstituted in its original volume can reverse trauma-associated coagulopathy. To enhance the logistical advantage (lower volume and weight), we developed and tested a hyperoncotic, hyperosmotic spray-dried plasma (SDP) product in a multiple injuries/hemorrhagic shock swine model.

Methods: Plasma separated from fresh porcine blood was stored as FFP or preserved as FDP and SDP. In in vitro testing, SDP was reconstituted in distilled water that was either equal (1 × SDP) or one-third (3 × SDP) the original volume of FFP. Analysis included measurements of prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen levels, and activity of selected clotting factors. In in vivo testing, swine were subjected to multiple injuries (femur fracture and grade V liver injury) and hemorrhagic shock (60% arterial hemorrhage, with the "lethal triad" of acidosis, coagulopathy, and hypothermia) and were treated with FFP, FDP, or 3 × SDP (n=4-5/group). Coagulation profiles (PT, PTT, and thromboelastography) were measured at baseline, post-shock, post-crystalloid, treatment (M0), and during 4 hours of monitoring (M1-4).

Results: In vitro testing revealed that clotting factors were preserved after spray drying. The coagulation profiles of FFP and 1 × SDP were similar, with 3 × SDP showing a prolonged PT/PTT. Multiple injuries/hemorrhagic shock produced significant coagulopathy, and 3 × SDP infusion was as effective as FFP and FDP in reversing it.

Conclusion: Plasma can be spray dried and reconstituted to one-third of its original volume without compromising the coagulation properties in vivo. This shelf-stable, low-volume, hyperoncotic, hyperosmotic plasma is a logistically attractive option for the treatment of trauma-associated coagulopathy in austere environments, such as a battlefield.