Efficacy and safety of lyophilized plasma in prehospital emergency care for victims of accidents: a literature review

Relevance. Emergency accidents of natural and technogenic nature, including maritime accidents, are often characterized by significant sanitary losses and various injuries, frequently involving with acute massive blood loss. In emergency situations the latter is a leading cause of death in severely injured patients, often leading to the development of hypocoagulation. To address hypocoagulation, medications and blood components, including lyophilized (freeze–dried) plasma, are utilized. However, current data regarding the effectiveness and safety of such emergency medical care in pre–hospital settings remain contradictory.

The objective is to conduct an analytical review to evaluate the effectiveness and safety of lyophilized plasma the clinical setting of prehospital emergency medical care provided to victims of emergency accidents.

Methods. The research used scientific publications from open access databases (eLibrary.ru, PubMed). The studies based on registered controlled clinical trials were analyzed to evaluate the efficacy and safety of lyophilized plasma administered in prehospital emergency settings. In addition, we investigated annual reports on posttransfusion reactions and complications, available in international and national blood safety surveillance systems.

Results and discussion. The analysis of randomized clinical trials and results did not reveal statistically significant differences in clinical outcomes, complication rates, or severity of coagulopathy in patients receiving lyophilized plasma in prehospital emergency medical care for injuries and wounds in peacetime, in comparison with patients receiving standard treatment. However, available observational studies suggest that lyophilized plasma can effectively used in patients with injuries and bleeding in prehospital emergency care, including during ground and air medical evacuation. Reports of posttransfusion reactions and complications associated with lyophilized plasma transfusion remain incompletely accounted for and are characterized by a low degree of evidence.

Conclusion. The results of clinical studies support the feasibility of using lyophilized plasma in adult patients at risk of post–traumatic coagulopathy at the pre–hospital stage of emergency medical care in peacetime. Nonetheless, comprehensive evaluation of the efficacy and safety of lyophilized plasma administration in such patients requires further randomized clinical trials, involving different patient cohorts in various emergency scenarios.

1. Berkovskiy A.L., Sergeeva E.V., Suvorov A.V. [et al.]. Poluchenie liofilizirovannoi plazmy s sokhranennoi aktivnost’yu faktorov svertyvaniya [The development and modification of preparations for the treatment of hemophilia]. Gematologiya i transfuziologiya [Russian journal of hematology and transfusiology]. 2016; 61(4):204–208. DOI: 10.18821/0234-5730-201661-4-204-208. (In Russ)

2. Bondaruk O.N., Dashkevich E.V., Pasyukov V.V. Liofilizirovannaya plazma: otsenka effektivnosti i bezopasnosti [Lyophilized plasma: efficiency and safety evaluation]. Gematologiya. Transfuziologiya. Vostochnaya Evropa [Hematology. Transfusiology. Eastern Europe]. 2021; 7(1):49– 59. DOI: 10.34883/PI.2021.7.1.004. (In Russ)

3. Korobushkin G.V., Shigeev S.V., Zhukov A.I. Analiz prichin smerti v vyborke patsientov s politravmoi v Moskve [Analysis of causes of death in a sample of patients with polytrauma in Moscow]. Politravma [Polytrauma]. 2020; (2):47–53. DOI: 10.24411/1819-1495-2020-10019. (In Russ)

4. Krivov I.A., Ragimov A.A., Salimov E.L. Sravnenie vliyaniya liofilizatsii na pokazateli plazmennogo gemostaza v virusinaktivirovannoi razlichnymi metodami plazme krovi [Comparison of the effect of lyophilization on plasma hemostasis parameters in virusinactivated blood plasma inactivated by various methods]. Sovremennye problemy nauki i obrazovaniya [Modern problems of science and education]. 2021: (2). DOI: 10.17513/spno.30630. (In Russ)

5. Sarkisov I.Yu., Sarkisov A.I., Berkovskii A.L. [et al.]. Innovatsionnaya otechestvennaya tekhnologiya polucheniya liofilizirovannoi plazmy [Innovative domestic technology for obtaining lyophilized plasma]. Transfuziologiya. [Transfusiology]. 2022; (3-1):48–49. (In Russ)

6. Stepanov S.S., Girsh A.O., Stukanov M.M. [et al.]. Personalizatsiya programm infuzionnoi terapii u bol’nykh s tyazhelym travmaticheskim shokom na dogospital’nom etape [The statistical importance of influence of various options of infusional therapy on parameters of a homeostasis of patients with heavy traumatic shock]. Skoraya meditsinskaya pomoshch [Emergency medical care]. 2022: 23(3):17–23. DOI: 10.24884/20726716-2022-23-3-17-23. (In Russ)

7. Chechetkin A.V., Alekseeva N.N., Staritsyna N.N. [et al.]. Proizvodstvo i primenenie liofilizirovannoi plazmy: istoricheskie aspekty i sovremennoe sostoyanie [Production and use of lyophilized plasma: historical aspects and current state]. Transfuziologiya [Transfusiology]. 2018: 4):67–75. (In Russ)

8. Shabunin A.V., Rodionov E.P., Grekov D.N. [et al.]. Organizatsiya okazaniya spetsializirovannoi meditsinskoi pomoshchi pri politravme v mnogoprofil’noi bol’nitse [Organization of provision of specialized medical care for polytrauma in multidisciplinary hospital]. Meditsinskii alfavit [Medical alphabet]. 2021; (25):34– 41. DOI: 10.33667/2078-5631-2021-25-34-41. (In Russ)

9. Shapkin Yu.G., Seliverstov P.A., Stekol’nikov N.Yu., Ashevskii V.V. Dogospital’naya pomoshch’ po printsipam Damage Control Resuscitation v usloviyakh sovremennykh boevykh deistvii (obzor literatury) [Prehospital care according to the principles of Damage Control Resuscitation in the conditions of modern warfare (literature review)]. Mediko-biologicheskie i sotsial’nopsikhologicheskie problemy bezopasnosti v chrezvychainykh situatsiyakh [Medicо-Biological and Socio-Psychological Problems of Safety in Emergency Situations]. 2022; (4):55–65. DOI: 10.25016/2541-7487-2022-0-4-55-65. (In Russ)

10. Shchegolev A. V., Gritsai A. N., Klimov A.G. [et al.]. Osobennosti infuzionnoi terapii na dogospital’nom etape pri prodolzhayushchemsya krovotechenii [Features of the infusion therapy at the prehospital stage with the ongoing bleeding]. Skoraya meditsinskaya pomoshch [Emergency medical care]. 2021; 22(3):71–78. DOI: 10.24884/2072-6716-2021-22-3-71-78. (In Russ)

11. Adams P.W., Warren K.A., Guyette F.X. [et al.]. Implementation of a prehospital air medical thawed plasma program: Is it even feasible? J. Trauma Acute Care Surg. 2019; 87(5):1077–1081. DOI: 10.1097/TA.0000000000002406.

12. Ångerman S., Kirves H., Nurmi J. Characteristics of non trauma patients receiving prehospital blood transfusion with the same triggers as trauma patients: a retrospective observational cohort study. Prehospital Emerg. Care. 2022; 26(2):263–271. DOI: 10.1080/10903127.2021.1873472.

13. Bux J., Dickhörner D., Scheel E. Quality of freeze-dried (lyophilized) quarantined single-donor plasma. Transfusion. 2013; 53(12):3203–3209. DOI: 10.1111/trf.12191.

14. Cancelas J.A., Nestheide S., Rugg N. [et al.]. Characterization and first-in-human clinical dose-escalation safety evaluation of a next-gen human freeze-dried plasma. Transfusion. 2022; 62(2):406–417. DOI: 10.1111/trf.16756.

15. Chang R., Cardenas J.C., Wade C.E., Holcomb J.B. Advances in the understanding of trauma-induced coagulopathy. Blood. 2016; 128(8):1043–1049. DOI: 10.1182/blood-2016-01-636423.

16. Crombie N., Doughty H., Bishop J.R.B. [et al.]. Resuscitation with blood products in patients with traumarelated haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Haematol. 2022; 9(4):e250–e261. DOI: 10.1016/S2352-3026(22)00040-0.

17. Fecher A., Stimpson A., Ferrigno L., Pohlman T.H. The pathophysiology and management of hemorrhagic shock in the polytrauma patient. J. Clin. Med. 2021; 10(20):4793–4820. DOI: 10.3390/jcm10204793.

18. Feuerstein S.J., Skovmand K., Møller A.M., Wildgaard K. Freeze-dried plasma in major haemorrhage: a systematic review. Vox. Sang. 2020; 115(4):263–274. DOI: 10.1111/vox.12898.

19. Flaumenhaft E.J., Khat T., Marschner S. Retention of coagulation factors and storage of freeze-dried plasma. Mil. Med. 2021; 186(1):400–407. DOI: 10.1093/milmed/usaa347.

20. Garcia J., Carneiro A.C.D.M., Silva S.S. Underreporting of transfusion incidents. Hematol. Transfus. Cell Ther. 2024; 46(2):186–191. DOI: 10.1016/j.htct.2024.01.004.

21. Garrigue D., Godier A., Glacet A. [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; 16(3):481–489. DOI: 10.1111/jth.13929.

22. Heger A., Gruber G. Frozen and freeze-dried solvent/detergent treated plasma: Two different pharmaceutical formulations with comparable quality. Transfusion. 2022; 62(12):2621–2630. DOI: 10.1111/trf.17139.

23. Holcomb J.B., Donathan D.P., Cotton B.A. [et al.]. Prehospital transfusion of plasma and red blood cells in trauma patients. Prehosp. Emerg. Care. 2015; 1(1):1–9. DOI: 10.3109/10903127.2014.923077.

24. ISBT working party on haemovigilance. Proposed standard definitions for surveillance of non infectious adverse transfusion reactions. URL: https://www.isbtweb.org/static/0fa5485b-5dcc-4e85-a3d61ce8db17d504.

25. Jama T., Lefering R., Lauronen J., Handolin L. Factors affecting physicians’ decision to start prehospital blood product transfusion in blunt trauma patients: A cohort study of Helsinki Trauma Registry. Transfusion. 2024; 64(2):S167–S173. DOI: 10.1111/trf.17791.

26. Jost D., Lemoine S., Lemoine F. [et al.]. Prehospital lyophilized plasma transfusion for trauma-induced coagulopathy in patients at risk for hemorrhagic shock. A randomized clinical trial. JAMA Network Open. 2022; 5(7):e2223619. DOI: 10.1001/jamanetworkopen.2022.23619.

27. Mitra B., Meadley B., Bernard S. [et al.]. Pre-hospital freeze-dried plasma for critical bleeding after trauma: a pilot randomized controlled trial. Acad. Emerg. Med. 2023; 30(10):1013–1019. DOI:10.1111/acem.14745.

28. Mould-Millman N-K., Wogu A.F., Fosdick B.K. [et al.]. Association of freeze-dried plasma with 24-h mortality among trauma patients at risk for hemorrhage. Transfusion. 2024; 64(2):S155–S166. DOI: 10.1111/trf.17792.

29. Nguyen C., Bordes J., Cungi P. [et al.]. Use of French lyophilized plasma transfusion in severe trauma patients is associated with an early plasma transfusion and early transfusion ratio improvement. J. Trauma Acute Care Surg. 2018; 84(5):780–787. DOI: 10.1097/TA.0000000000001801.

30. Oakeshotta J.E., Griggsa G.M., Warehama R.M. Feasibility of prehospital freeze-dried plasma administration in a UK Helicopter Emergency Medical Service. Eur. J. Emerg. Med. 2019; 26(5):373–378. DOI: 10.1097/MEJ.0000000000000585.

31. Peng H.T., Singh, K., Rhind S.G. [et al.]. Dried plasma for major trauma: past, present, and future. Life. 2024; 14(5):619–654. DOI: 10.3390/life14050619.

32. Pusateri A.E., Malloy W.W., Sauer D. [et al.]. Use of dried plasma in prehospital and austere environments. Anesthesiology. 2022; 136(2):327–335. DOI: 10.1097/ALN.0000000000004089.

33. Singh K., Peng H.T., Moes K. [et al.]. Past meets present: reviving 80-year-old Canadian dried serum from World War II and its significance in advancing modern freeze-dried plasma for prehospital management of haemorrhage. Br. J. Haematol. 2024; 204(4):1515–1522. DOI: 10.1111/bjh.19298.

34. Shlaifer A., Siman-Tov M., Radomislensky I. Prehospital administration of freeze-dried plasma, is it the solution for trauma casualties? J. Trauma Acute Care Surg. 2017; 83(10):675–682. DOI: 10.1097/TA.0000000000001569.

35. Steil L., Thiele T., Hammer E. [et al.]. Proteomic characterization of freeze-dried human plasma: providing treatment of bleeding disorders without the need for a cold chain. Transfusion. 2008; 48(11):2356–2363. DOI: 10.1111/j.1537-2995.2008.01856.x.

36. Strauss R., Menchetti I., Perrier L., [et al.]. Evaluating the Tactical Combat Casualty Care principles in civilian and military settings: systematic review, knowledge gap analysis and recommendations for future research. Trauma Surg. Acute Care Open. 2021; 19(6):e000773. DOI: 10.1136/tsaco-2021-000773.

37. Sunde G., Vikenes B., Strandenes G. [et al.]. Freeze dried plasma and fresh red blood cells for civilian prehospital hemorrhagic shock resuscitation. J. Trauma Acute Care Surg. 2015; 78(6, Supll. 1):S26–S30. DOI: 10.1097/TA.0000000000000633.

38. Thies K.C., Truhlar A., Keene D. [et al.]. Pre-hospital blood transfusion: An ESA survey of European practice. Scand. J. Trauma Resusc. Emerg. Med. 2020; 28(1):797–805. DOI: 10.1186/s13049-020-00774-1

39. Vuorinen P., Kiili J.E., Setаlа P. [et al.]. Prehospital administration of blood products: experiences from a Finnish physician-staffed helicopter emergency medical service. BMC Emerg. Med. 2020; 20(1):55–61. DOI: 10.1186/s12873-020-00350-x.

40. Yliharju H., Jama T., Nordquist H. Initial experiences of prehospital blood product transfusions between 2016 and 2020 in Päijät Häme hospital district, Finland. Scand. J. Trauma Resusc. Emerg. Med. 2022; 30(6):39–48. DOI: 10.1186/s13049-022-01027.

41. Zielinski M.D., Stubbs J.R., Berns K.S. [et al.]. Prehospital blood transfusion programs: capabilities and lessons learned. J. Trauma Acute Care Surg. 2017; 82(6-1):S70–S78. DOI: 10.1097/TA.0000000000001427.