Evaluation of the efficacy and safety of lyophilized plasma

Objective. To assess the hemostatic potential, preclinical safety and in vitro efficacy of lyophilized plasma in patients and blood donors.
Materials and methods. The study of acute toxicity was carried out on outbred mice of both sexes (n=120), pyrogenicity – on rabbits of both sexes (n=30), abnormal toxicity – on mice (n=25) and guinea pigs (n=6). Histopathological studies were carried out on preparations of five fragments of the middle part of the mouse tail after intravenous administration of the maximum dose (4500 mg/kg) lyophilized plasma (LP), physiological solution, fresh frozen plasma (FFP) and pathogen-reduced FFP (PRFFP) using the Intercept system. The proand anticoagulant activity was investigated by clotting and chromogenic method to evaluate the hemostatic potential of PL. The effect on hemostasis was studied in vitro by thromboelastometry when FFP and LP were added to blood samples of patients (n = 23) and donors (n = 20). Results. Acute toxicity study showed the absence of death and clinical signs of intoxication in all series. On the 14th day, body weight gain was observed in animals of all series. Regardless of the used LP dosage, no development of effusion and adhesions in the thoracic and abdominal cavities, as well as macroscopically detectable pathologic changes of the main organs were observed in animals. The analysis of the relative weight of internal organs of animals did not reveal statistically significant differences in experimental and control series relative to the values of similar indicators in intact animals. The studied hemostatic potential showed that LP was not inferior to PRFFP in the content of coagulation factors of the blood system. Evaluation of the effect of LP application in vitro in female patients showed statistically significant correction of CT (clotting time) index, which indicates the effectiveness of its application for replenishment of blood coagulation factors (BCF).
Conclusion. Preclinical animal studies of LP have proven its safety and efficacy compared to FFP.

1. Dashkevich EV, Klimkovich NN. The use of blood components in transfusion-significant syndromes as a standard of medical practice. Hematology. Transfusiology. Eastern Europe. 2022;8(4):471-479. (In Russ.).

2. Sahmoud S, Ashry EM, El Kalioby M, Kamel N. Knowledge Improvement of Blood Transfusion Safety Among Pediatricians: Post Educational Intervention. Transfus Med Rev. 2021 Apr;35(2):135-139. DOI: https://doi.org/10.1016/j.tmrv.2021.03.002

3. Garcia J, Silva SS, Meneguci J, Moraes-Souza H. Profile of hemotherapy care and the safety of the transfusion process. Rev Assoc Med Bras. 2022;68(6):770-774. DOI: https://doi.org/10.1590/1806-9282.20211246

4. Resolution of the Ministry of Health of the Republic of Belarus dated May 19, 2023 No. 92 «On approval of the Instructions on the procedure for the use of blood and (or) its components in healthcare organizations». [date of access 2021 august 01]. Available from: https://pravo.by/document/?guid=12551&p0=W22340218 (In Russ.).

5. Resolution of the Ministry of Health of the Republic of Belarus dated May 19, 2023 No. 89 «On the quality of blood and (or) its components and the nomenclature of blood and (or) its components». [date of access 2021 august 01]. Available from: https://minzdrav.gov.by/upload/lcfiles/%D0%BF%D0%BE%D1%81%D1%82%D0%B0%D0%BD%D0%BE%D0%B2%D0%BB%D0%B5%D0%BD%D0%B8%D0%B5_%D0%9C%D0%97_2023_89.pdf (In Russ.).

6. Garrigue D, Godier A, Glacet A, Labreuche J, Kipnis E, et al. French lyophilized plasma versus fresh frozen plasma for the initial management of trauma-induced coagulopathy: a randomized open-label trial. J Thromb Haemost. 2018 Mar;16(3):481-489. DOI: https://doi.org/10.1111/jth.13929

7. Jamison Beiriger, David Silver, Joshua B. Brown. Transfusion Management in Trauma: What is Current Best Practice? Current Surgery Reports. 2023;11:43-54. DOI: https://doi.org/10.1007/s40137-023-00352-1

8. Bondaruk ON, Dashkevich EV, Pasyukov VV. Lyophilized plasma: assessment of effectiveness and safety. Hematology. Transfusiology. Eastern Europe. 2021;7(1):49-59. (In Russ.).

9. Popovsky MA, White N. Spray-dried plasma: A post-traumatic blood “bridge” for life-saving resuscitation. Transfusion. 2021;61:S294-S300. DOI: https://doi.org/10.1111/trf.16536

10. Mok G, Hoang R, Khan MW, Pannell D, Peng H, Tien H, et al. Freeze-dried plasma for major trauma Systematic review and meta-analysis. J Trauma Acute Care Surg. 2021 Mar 1;90(3):589-602. DOI: https://doi.org/10.1097/TA.0000000000003012

11. Roshchina E.A. Reference intervals for mass coefficients of mouse organs and their absolute values. Laboratory animals for scientific research. 2022;(3):24-29. (In Russ.). DOI: https://doi.org/10.57034/2618723X-2022-03-03

12. Hellstern P, Sachse H, Schwinn H, Oberfrank K. Manufacture and in vitro characterization of a solvent/detergent-treated human plasma. Vox Sang. 1992;63(3):178-185. DOI: https://doi.org/10.1111/j.1423-0410.1992.tb05097.x

13. Yarets YuI. Thromboelastography: main indicators, interpretation of results. Gomel: State Institution “RSPC RMiECH”; 2018. 26 p. (In Russ.).