Ex vivo hemostatic and immuno‐inflammatory profiles of freeze‐dried plasma

Abstract

Background Hemorrhage is a leading cause of preventable death in civilian and military trauma. Freeze‐dried plasma is promising for hemostatic resuscitation in remote prehospital settings, given its potential benefits in reducing blood loss and mortality, long storage at ambient temperatures, high portability, and rapid reconstitution for transfusion in austere environments. Here we assess the ex vivo characteristics of a novel Terumo's freeze‐dried plasma product (TFDP). Study design and methods Rotational thromboelastometry (ROTEM) tests (INTEM, EXTEM, and FIBTEM) were conducted on plasma samples at 37°C with a ROTEM delta‐machine using standard reagents and procedures. The following samples were analyzed: pooled plasma to produce TFDP, TFDP reconstituted, and stored immediately at −80°C, reconstituted TFDP stored at 4°C for 24 h and room temperature (RT) for 4 h before freezing at −80°C. Analysis of plasma concentrations of selected cytokines, chemokines, and vascular molecules was performed using a multiplex immunoassay system. One‐way ANOVA with post hoc tests assessed differences in hemostatic and inflammatory properties. Results No significant differences in ROTEM variables (coagulation time [CT], clot formation time, α‐angle, maximum clot firmness, and lysis index 30) between the TFDP‐producing plasma and reconstituted TFDP samples were observed. Compared to control plasma, reconstituted TFDP stored at 4°C for 24 h or RT for 4 h showed a longer INTEM CT. Levels of immuno‐inflammatory mediators were similar between frozen plasma and TFDP. Conclusions TFDP is equivalent to frozen plasma with respect to global hemostatic and immuno‐inflammatory mediator profiles. Further investigations of TFDP in trauma‐induced coagulopathy models and bleeding patients are warranted.

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

“…Taken together, we conclude that losses of procoagulant or anticoagulant activities were similar in Canadian TFDP versus licensed FDP products. While this work was in progress, our collaborators Peng et al published a report demonstrating no difference in thromboelastometric parameters between Canadian TFDP and the FP pools from which it was made, reinforcing this conclusion 30 …”

Freeze‐dried plasma: From damage control resuscitation to coronavirus disease 2019 therapy

“…In addition, both CC-FFP and CC-FDP contain high concentrations of functional SARS-CoV-2 neutralizing IgG and that antibody levels are preserved in CC-FDP. The current study augments our previous findings 18 and replicates another lab investigation on the same sample set 21 by employing additional ROTEM and Stago hemostatic tests, and novel MSD anti-SARS-CoV-2 serological immunoassays.…”

“…17 In a previous report, we have shown retention of global hemostatic functions and immuno-inflammatory activities of FDP produced from pre-COVID-19-FFP using a Terumo Blood and Cell Technologies (BCT) lyophilizing system. 18 We hypothesized that FDP generated using the lyophilizing process would retain similar levels of coagulation factors and other plasma proteins including antibodies against COVID-19 to its plasma source. Here, we present the in vitro hemostatic and immunological characterization of FFP, CCP, and their corresponding FDP, as measured by Rotational Thromboelastometry (ROTEM) and Stago coagulation assays, and Meso Scale Diagnostics serological immunoassay system.…”

Characterization and first‐in‐human clinical dose‐escalation safety evaluation of a next‐gen human freeze‐dried plasma

“…In addition, no FDP product is currently licensed by the US FDA 26 . Recent efforts to manufacture FDP in plastic bags for transfusion and their in vitro characterization have been reported 27,28 . However, none of these modern FDP products have been tested in humans.…”