Optimal storage conditions of platelet concentrate considering metabolic activity: original article

INTRODUCTION. The quality of procured hemotransfusion components is largely achieved by the effective application of modern equipment, rational use of donor potential, as well as the introduction of new transfusion technologies. However, maintaining the metabolic properties of platelets, along with minimal activation during the actual storage time, remains a problem in blood transfusion services.

OBJECTIVE. To evaluate, considering storage times under different temperature conditions, the metabolic level in platelet concentrate (PC) prepared in plasma and in SSP+ supplement solution.

MATERIALS AND METHODS. The object of the study were 20 PC samples prepared by automatic apheresis in plasma and the same number in SSP+ supplemental solution (MacoPharma, France) under conditions of reduced temperature (4 ± 2 °C) on the day of preparation and for storage periods up to 15 days. In the room temperature regime, 25 PT samples in plasma and 31 in SSP+ supplement solution were included in the study on the day of preparation and on the 5th day of storage. A total of 96 PC samples were investigated. The number of platelets was determined on the automatic hematological analyzer Medonic M20 (Sweden). Parameters of platelet metabolism in vitro (pH, glucose and lactate levels) were measured using a blood gas analyzer ABL-800 Flex (Radiometer, Denmark). To identify the number of platelet microparticles we used the method of flow cytometry with anti-CD41 - APC (Clone MEM-06) to platelet surface markers on a CytoFlex analyzer (Beckman Coulter, USA).

RESULTS. The possibilities and advantages of a rational approach to PC transfusion were revealed, taking into account the medium of content, degree of activation and temperature regime of platelet storage to optimize the component procurement. The data obtained on the 1st-5th day during cold storage of PC coincide with the study of storage at a regulated temperature of 22 ± 2 ºC and constant stirring. Special attention is paid to the amount of platelet microparticles by the end of the storage period. It is noteworthy that their content in both groups significantly increased compared to the initial one, indicating an increase in platelet activation by the end of the storage period.

DISCUSSION. The evaluation of metabolic activity revealed that, regardless of storage medium and temperature conditions, platelets retained metabolic activity for 5 days without exceeding the regulated pH values. The content of microparticles is an indicator of the proportion of active platelets in a given concentrate. It is likely that regular donations from active donors could potentially be associated with cellular activation and an increase in the number of circulating microparticles in PC. The data from this study emphasize the need to develop and justify requirements for harvesting and storage of PC with regard to activation status based on screening of microparticles in donors. The possibility of differentiating PC based on screening of the content of microparticles resulting from activation will help to improve the efficiency and safety of transfusion therapy.

CONCLUSION. Platelet concentrates have a short shelf life and are often in limited quantities. PC stock management based on platelet and microparticle content analysis is a promising strategy, which is also important for marine professionals. Assessment of PC activation status by the level of microparticle content will improve the quality and efficiency of the transfusion therapy performed and optimize the use of the sought-after blood component.

1. Maurer-Spurej E., Chipperfield K. Past and future approaches to assess the quality of platelets for transfusion. Transfus Med Rev, 2007, 21(4), pp. 295–306. doi: 10.1016/j.tmrv.2007.05.005.

2. Holmsen H., Setkowsky C. A., Day H. J. Влияние антимицина и 2-дезоксиглюкозы на адениновые нуклеотиды в тромбоцитах человека. Роль метаболического аденозинтрифосфата в первичной агрегации, вторичной агрегации и изменении формы тромбоцитов. Biochem J, 1974, Vol. 144, pp. 385–396.

3. Kramer P. A., Ravi S., Chacko B., Johnson M. S., Darley-Usmar V. M. A review of the mitochondrial and glycolytic metabolism in humanplatelets and leukocytes: implications for their use as bioenergetics biomarkers. Redox Biol, 2014, Vol. 10, No. 2, pp. 206–210.

4. Ravi S., Chacko B., Sawada H., Kramer P. A., Johnson M. S., Benavides G. A., et al. Metabolic Plasticity in Resting and Thrombin Activated Platelets. PLoS ONE, 2015, 10(4), e 0123597.

5. Corona de la Peña N., Gutiérrez-Aguilar M., Hernández-Reséndiz I., Marı́n-Hernández A., Rodriguez-Enriquez S. Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets. PLoS One, 2017, 12(8), e 0182374.

6. Paglia G., Sigurjónsson Ó. E., Rolfsson Ó., Valgeirsdottir S., Hansen M. B., Brynjólfsson S., Gudmundsson S., Palsson B.O. Comprehensive metabolomic study of platelets reveals the expression of discrete metabolic phenotypes during storage. Transfusion, 2014, Vol. 54, 2911–2923. doi:10.1111/trf.12710.

7. George C. E., Saunders C. V., Morrison A., Scorer T., Jones S., Dempsey N. C. Cold stored platelets in the management of bleeding: is it about bioenergetics? Platelets, 2023, 34(1), pp. 2188969. doi: 10.1080/09537104.2023.2188969. PMID: 36922733.

8. Reddoch K. M., Pidcoke H. F., Montgomery R. K., et al. Hemostatic function of apheresis platelets stored at 4 С and 22 С. Shock, 2014, Vol. 41, Nо. 1(01), pp. 54–61.

9. Braathen H., Sivertsen J., Lunde T. H. F., et al. In vitro quality and platelet function of cold and delayed cold storage of apheresis platelet concentrates in platelet additive solution for 21 days. Transfusion, 2019, Vol. 59, Nо. 8, pp. 2652–2661.

10. Getz T. M., Montgomery R. K., Bynum J. A., et al. Storage of platelets at 4 °С in platelet additive solutions prevents aggregate formation and preserves platelet functional responses. Transfusion, 2016, Vol. 56, Nо. 6, pp.1320–1328.

11. Bynum J. A., Meledeo M. A., Getz T. M., Rodriguez A. C., Aden J. K., Cap A. P., Pidcoke H. F. Bioenergetic profiling of platelet mitochondria during storage: 4°C storage extends platelet mitochondrial function and viability. Transfusion, 2016, Vol. 56, Suppl 1, S76–S84. doi: 10.1111/trf.13337. PMID: 27001365.

12. Zharikov S., Shiva S. Platelet Mitochondrial Function: From Regulation of Thrombosis to Biomarker of Disease. Biochem. Soc. Trans, 2013, Vol. 41, pp.118–123. doi: 10.1042/BST20120327.

13. Ravera S., Signorello M. G., Bartolucci M., Ferrando Ravera S., Signorello M. G., Panfoli I. Platelet Metabolic Flexibility: A Matter of Substrate and Location. Cells, 2023, 12(13), pp. 1802. doi: 10.3390/cells12131802.

14. Ravera S., Signorello M. G., Bartolucci M., Ferrando S., Manni L., Caicci F., Calzia D., Panfoli I., Morelli A., Leoncini G. Extramitochondrial Energy Production in Platelets. Biol. Cell., 2018, Vol. 110, pp. 97–108. doi: 10.1111/boc.201700025.

15. Fuentes E., Araya-Maturana R., Urra F. A. Regulation of mitochondrial function as a promising target in platelet activation-related diseases. Free Radic Biol Med, 2019, Vol. 136, pp.172–182. doi: 10.1016/j.freeradbiomed.2019.01.007.

16. Prakhya K. S., Vekaria H., Coenen D. M., Omali L., Lykins J., Joshi S., Alfar H.R., Wang Q.J., Sullivan P., Whiteheart S.W. Platelet Glycogenolysis Is Important for Energy Production and Function. Platelets, 2023, Vol. 34, pp. 2222184. doi: 10.1080/09537104.2023.2222184.

17. Flora GD, Nayak MK, Ghatge M, Chauhan AK. Metabolic targeting of platelets to combat thrombosis: dawn of a new paradigm? Cardiovasc Res, 2023, 119(15), pp. 2497–2507. doi: 10.1093/cvr/cvad149.

18. Aibibula M., Naseem K. M., Sturmey R. G. Glucose Metabolism and Metabolic Flexibility in Blood Platelets. J. Thromb. Haemost., 2018, Vol. 16, pp. 2300–2314. doi: 10.1111/jth.14274.

19. Sake C. L., Metcalf A. J., Meagher M., Di Paola J., Neeves K. B., Boyle N. R. Isotopically Nonstationary 13C Metabolic Flux Analysis in Resting and Activated Human Platelets. Metab. Eng, 2022, Vol. 69, pp. 313–322. doi: 10.1016/j.ymben.2021.12.007.

20. Fuentes E., Araya-Maturana R., Urra F. A. Regulation of mitochondrial function as a promising target in platelet activation-related diseases. Free Radic Biol Med, 2019, Vol. 136, pp. 172–182. doi: 10.1016/j.freeradbiomed.2019.01.007.

21. Sut C., Aloui C., Tariket S., et al. Assessment of soluble platelet CD40L and CD62P during the preparation process and the storage of apheresis platelet concentrates: Absence of factors related to donors and donations. Transfus. Clin. Biol, 2018, 25(3), pp. 192–196. doi: 10.1016/j.tracli.

22. Burger D., Oleynik P. Isolation and characterization of circulating microparticles by flow cytometry. Hypertension, 2017, Vol. 1527, pp. 271–281. doi: 10.1007/978-1-4939-6625-7_21.

23. Khaliulin A. V., Gusyakova O. A., Kozlov A. V., Gabril’chak A. I. Metabolic processes and mechanisms of platelet activity regulation (literature review). Clinical laboratory diagnostics, 2019, 64 (3), pp. 164–169 (In Russ)].

24. Chen F, Liao Z, Peng D, Han L. Role of Platelet Microparticles in Blood Diseases: Future Clinical Perspectives. Ann Clin Lab Sci, 2019, 49(2), pp. 161–170. PMID: 31028059.

25. Chechetkin A. V., Alekseeva N. N., Staricyna N. N., Kiseleva E. A., Grishina G. V., et al. To study the morphofunctional properties of platelets during their storage in an additional solution containing sodium fumarate. Translational medicine, 2020, Vol. 7, No. 2, pp. 33–41 (In Russ)].

26. Leitner G.C., List J., Horvath M. Additive solutions differentially affect metabolism and functional parameters of platelet concentrates. Vox Sang, 2016, Vol. 110, Nо. 1, pp. 20–26. doi: 10.1111/vox.12317. Epub 2015 Aug 14.

27. Nogava M., Naito Y., Chatani M. Parallel comparison of apheresis-collected platelet concentrates stored in four different additive solutions. Vox Sang, 2013, Vol. 105, Nо. 4, pp. 305–312.

28. Garraud O., Cognasse F., Tissot J., et al. Improving platelet transfusion safety: biomedical and technical considerations. Blood Transfus, 2016, Vol. 14, pp. 109–122.

29. Shander A., Goobie S. M., Warner M. A., et al. Essential Role of Patient Blood Management in a Pandemic: A Call for Action. Anesthesia Analg, 2020, Vol. 131, No. 1, pp. 74–85.

30. Ngo A., Masel D., Cahill C., et al. Blood Banking and Transfusion Medicine Challenges During the COVID-19 Pandemic. Clin. Lab. Med, 2020, Vol. 40, No. 4, pp. 587–601.

31. Warner M. A., Kurian E. B., Hammel S. A., et al. Transition from room temperature to cold-stored platelets for the preservation of blood inventories during the COVID-19 pandemic. Transfusion, 2020, Vol. 61, No. 1, pp. 72–77.

32. Strandenes G., Sivertsen J., Bjerkvig C. K., et al. A Pilot Trial of Platelets Stored Cold versus at Room Temperature for Complex Cardiothoracic Surgery. Anesthesiology, 2020, Vol., 133, No. 6, pp. 1173–1183.

33. ГGrishina G. V., Lastochkina D. V., Kas’yanov A. D., Golovanova I. S., Bessmel’tsev S. S. Evaluation of microparticles in platelet concentrate depending on pathogen reduction: a pilot study. Marine Medicine, 2025, Vol. 11, No. 1, pp. 104–111 (In Russ)]. doi: https://dx.doi.org/10.22328/2413-5747-2025-11-1-104-111; EDN: https://elibrary.ru/GSAHEM.

34. Noulsri E. Effects of cell-derived microparticles on immune cells and potential implications in clinical medicine. Lab Med, 2020, Nо. 20, pp. 1–14. https://academic.oup.com/labmed/article/52/2/122/5894906?login=false.

35. Grishina G. V., Kas’yanov A. D., Lastochkina D. V., Krobinets I. I., Golovanova I. S., Matvienko O. Yu. Microparticles as quality criteria for platelet concentrate. Emergency medicine, 2024, Vol. 26, No. 4, pp. 132–140 (In Russ)]. https://doi.org/10.47183/mes.2024-26-4-132-140.

36. Ying Ng. M., Tung J. P., Fraser J. F. Platelet storage lesions: what more do we know now? Transfus. Med. Rev, 2018, Vol. 17, pp. 63–89.