Retention of hemostatic and immunological properties of frozen plasma and COVID-19 convalescent apheresis fresh-frozen plasma produced and freeze-dried in Canada.

BACKGROUND: Randomized clinical trial data show that early plasma transfusion may save lives among trauma patients. Supplying plasma in remote environments is logistically challenging. Freeze-dried plasma (FDP) offers a possible solution. STUDY DESIGN AND METHODS: A Terumo BCT plasma freeze-drying system was evaluated. We compared pooled frozen plasma (FP) units with derived Terumo BCT FDP (TFDP) units and pooled COVID-19 convalescent apheresis fresh-frozen plasma (CC-AFFP) with derived CC-TFDP units. Parameters measured were: coagulation factors (F) II; V; VII; VIII; IX; XI; XIII; fibrinogen; Proteins C (PC) and S (PS); antithrombin (AT); α2 -antiplasmin (α2 AP); ADAMTS13; von Willebrand Factor (vWF); thrombin-antithrombin (TAT); D-dimer; activated complement factors 3 (C3a) and 5 (C5a); pH; osmolality; prothrombin time (PT); and activated partial thromboplastin time (aPTT). Antibodies to SARS-CoV-2 in CC-AFFP and CC-TFDP units were compared by plaque reduction assays and viral protein immunoassays. RESULTS: Most parameters were unchanged in TFDP versus FP or differed ≤15%. Mean aPTT, PT, C3a, and pH were elevated 5.9%, 6.9%, 64%, and 0.28 units, respectively, versus FP. CC-TFDP showed no loss of SARS-CoV-2 neutralization titer versus CC-AFFP and no mean signal loss in most pools by viral protein immunoassays. CONCLUSION: Changes in protein activities or clotting times arising from freeze-drying were <15%. Although C3a levels in TFDP were elevated, they were less than literature values for transfusable plasma. SARS-CoV-2-neutralizing antibody titers and viral protein binding levels were largely unaffected by freeze-drying. In vitro characteristics of TFDP or CC-TFDP were comparable to their originating plasma, making future clinical studies appropriate.

Retention of Coagulation Factors and Storage of Freeze-Dried Plasma.

INTRODUCTION: Terumo BCT is developing a system to produce a freeze-dried plasma product, Terumo's freeze-dried plasma (TFDP), that is stored in a rugged, light-weight plastic package suitable for field use, which retains a stable level of specific coagulation factors and proteins within clinical range, when stored for up to 2 years at room temperature and 4°C. MATERIALS AND METHODS: Plasma frozen within 24 hours of phlebotomy (PF24) were thawed, sampled, and individually lyophilized to produce a corresponding TFDP unit. Fresh frozen plasma (FFP) units were thawed, sampled, pooled in groups of 10 units (also sampled) and lyophilized to produce 2 lots of TFDP. Each TFDP unit was reconstituted with water for injection (WFI) and tested for pH, prothrombin time, activated partial thromboplastin time, factors V and VIII, fibrinogen, protein C, and protein S. Results were compared with PF24/FFP. Additional FFP units were thawed, sampled, pooled, divided to generate 2 TFDP units for each time point (1, 2, 3, 6, 12, 18, and 24 months, one each stored at 4°C and 25°C) and lyophilized. Postlyophilization, TFDP units were stored at 4°C or 25°C, reconstituted with WFI, and tested for the factors listed above. Residual moisture content of the lyophilized plasma was also tested. RESULTS: Coagulation factor activity of TFDP was ±20% of PF24/FFP. Pooling standardized variation in TFDP coagulation factor activities, which were within clinical ranges postlyophilization. The pH of TFDP and PF24/FFP were within required range. Residual moisture content of TFDP was <2%. CONCLUSIONS: The TFDP process had no negative impact on coagulation factor activity. Input plasma and anticoagulant type did not affect TFDP quality. Pooling FFP normalized factor variability in TFDP and did not negatively impact product quality. The TFDP is stable for up to 24 months at room and refrigerated temperatures. Terumo's freeze-dried plasma is comparable to PF24/FFP. It does not require complex logistics or time-consuming thawing. Terumo's freeze-dried plasma may be suitable for rapid treatment of coagulopathies with logistical advantages over PF24/FFP.