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Roshanzamir F, Amini-kafiabad S, Mohajer Ansari J, Nikougoftar Zarif M, Arabkhazaeli A, Mohammadipour M. A Comparative Study of Quality Metrics in Leukoreduced Red Blood Cell Units Following Filtration with Two Distinct Inline Filter Blood Bags. bloodj 2025; 22 (4) :265-276
URL: http://bloodjournal.ir/article-1-1605-en.html
A Comparative Study of Quality Metrics in Leukoreduced Red Blood Cell Units Following Filtration with Two Distinct Inline Filter Blood Bags
Fateme Roshanzamir * , Sedigheh Amini-kafiabad , Javad Mohajer Ansari , Mahin Nikougoftar Zarif , Ali Arabkhazaeli , Mahshid Mohammadipour
Keywords: Erythrocyte Transfusion, Blood Component Removal, Storage Lesions, Red Blood Cells, Cell-derived Microparticles, Cell Separation 
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References:
  1. Rana M, Arfat Y, Naseem O, Mazari N, Manzoor N, Aziz RS, Rashid M, Mohsin S. Levels of red blood cells derived microparticles in stored erythrocyte concentrate. African Journal of Pharmacy and Pharmacology. 2020;14(6):185-91. [DOI:10.5897/AJPP2020.5126]
  2. Nikulina M, Nemkov T, D'Alessandro A, Gaccione P, Yoshida T. A deep 96-well plate RBC storage platform for high-throughput screening of novel storage solutions. Front Physiol. 2022;13:1004936. [DOI:10.3389/fphys.2022.1004936] [PMID] []
  3. World Health Organization. Global status report on blood safety and availability 2021. World Health Organization; 2022:1-51. [DOI:10.1007/978-3-030-05325-3_125-1]
  4. Ma SR, Xia HF, Gong P, Yu ZL. Red blood cell-derived extracellular vesicles: An overview of current research progress, challenges, and opportunities. Biomedicines. 2023;11(10):2798. [DOI:10.3390/biomedicines11102798] [PMID] []
  5. Westerman M, Porter JB. Red blood cell-derived microparticles: an overview. Blood Cells, Molecules, and Diseases. 2016; 59: 134-9. [DOI:10.1016/j.bcmd.2016.04.003] [PMID]
  6. Levin G, Sukhareva E, Lavrentieva A. Impact of microparticles derived from erythrocytes on fibrinolysis. Journal of thrombosis and thrombolysis. 2016; 41(3): 452-8. [DOI:10.1007/s11239-015-1299-y] [PMID]
  7. Jin Z, Yao S, Li L, Sun S, Zhou Y, Zhou J, Wang Z, Cui Z. Efficient leukocyte removal and enhanced biocompatibility using PVDF membranes prepared by vapor-induced phase separation. Chinese Journal of Chemical Engineering. 2025;89:1-12. [DOI:10.1016/j.cjche.2025.08.017]
  8. Silva ND, Nogueira LD, Nukui Y, Almeida-Neto CD. The effect of the leukoreduction filtration moment on the clinical outcome of transfused patients: A retrospective cohort study. Clinics. 2025; 2;80:100633. [DOI:10.1016/j.clinsp.2025.100633] [PMID] []
  9. Dejigov Monteiro da Silva N, Nukui Y, Takahashi J, de Almeida Lopes Monteiro da Cruz D, de Souza Nogueira L. Effect of post-storage filters vs. pre-storage filters for leukoreduction of blood components on clinical outcomes: a systematic review and meta-analysis. Systematic reviews. 2024;13(1):196. [DOI:10.1186/s13643-024-02615-z] [PMID] []
  10. Yang J, Yang Y, Gao L, Jiang X, Sun J, Wang Z, Xie R. Adverse effects of microparticles on transfusion of stored red blood cell concentrates. Hematology, Transfusion and Cell Therapy. 2024;46:S48-56. [DOI:10.1016/j.htct.2024.01.007] [PMID] []
  1. Almizraq RJ, Holovati JL, Acker JP. Characteristics of extracellular vesicles in red blood concentrates change with storage time and blood manufacturing method. Transfusion Medicine and Hemotherapy. 2018; 45(3): 185-193 [DOI:10.1159/000486137] [PMID] []
  2. Gao Y, Lv L, Liu S, Ma G, Su Y. Elevated levels of thrombin‐generating microparticles in stored red blood cells. Vox sanguinis. 2013; 105(1): 11-7. [DOI:10.1111/vox.12014] [PMID]
  3. Nguyen DB, Ly TBT, Wesseling MC, Hittinger M, Torge A, Devitt A, et al. Characterization of microvesicles released from human red blood cells. Cellular Physiology and Biochemistry. 2016; 38(3): 1085-99. [DOI:10.1159/000443059] [PMID]
  4. Xie R, Jia D, Gao C, Zhou J, Sui H, Wei X, et al. Homocysteine induces procoagulant activity of red blood cells via phosphatidylserine exposure and microparticles generation. Amino Acids. 2014; 46(8): 1997-2004. [DOI:10.1007/s00726-014-1755-6] [PMID]
  5. Sadeghi Neysiyani S, Amini-Kafiabad S, Hossieni E, Roshanzamir F. Activated Platelet and Platelet-Derived Microparticle Levels: A Comparative Study between Apheresis Platelet Concentrates and Pooled Platelet-Rich Plasma Platelet Concentrates. Indian Journal of Hematology and Blood Transfusion. 2026:42(1):222-228. [DOI:10.1007/s12288-025-01977-1] [PMID] []
  6. Roshanzamir F, Amini-Kafiabad S, Zarif MN, Arabkhazaeli A, Mohammadipour M. The potential effect of leukocyte filtration methods on erythrocyte-derived microvesicles: One step forward. European Journal of Translational Myology. 2022;32(3):10708. [DOI:10.4081/ejtm.2022.10708] [PMID] []
  7. Ghezelbash B, Azarkeivan A, Pourfathollah A, Deyhim M, Hajati E, Goodarzi A. Comparative evaluation of biochemical and hematological parameters of pre-storage leukoreduction during RBC storage. Int J Hematol Oncol Stem Cell Res. 2018; 12(1): 35.
  8. Almizraq RJ, Norris PJ, Inglis H, Menocha S, Wirtz MR, Juffermans N, et al. Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity. Blood advances. 2018; 2(18): 2296-306. [DOI:10.1182/bloodadvances.2018021931] [PMID]
  9. Almizraq R, Tchir JD, Holovati JL, Acker JP. Storage of red blood cells affects membrane composition, microvesiculation, and in vitro quality. Transfusion. 2013; 53(10): 2258-67. [DOI:10.1111/trf.12080] [PMID]
  10. Bicalho B, Pereira A, Acker J. Buffy coat (top/bottom)‐and whole‐blood filtration (top/top)‐produced red cell concentrates differ in size of extracellular vesicles. Vox Sang. 2015; 109(3): 214-20. [DOI:10.1111/vox.12272] [PMID]
  11. Hashemi Tayer A, Amirizadeh N, Ahmadinejad M, Nikougoftar M, Deyhim MR, Zolfaghari S. Procoagulant activity of red blood cell-derived microvesicles during red cell storage. Transfusion Medicine and Hemotherapy. 2019;46(4):224-30. [DOI:10.1159/000494367] [PMID] []
  12. Rubin O, Crettaz D, Tissot J-D, Lion N. Microparticles in stored red blood cells: submicron clotting bombs? Blood transfusion. 2010; 8(Suppl 3): s31.
  13. D'Alessandro A, Liumbruno G, Grazzini G, Zolla L. Red blood cell storage: the story so far. Blood Transfusion. 2010;8(2):82.
  14. Almizraq RJ, Seghatchian J, Acker JP. Extracellular vesicles in transfusion-related immunomodulation and the role of blood component manufacturing. Transfusion and Apheresis Science. 2016; 55(3): 281-91. [DOI:10.1016/j.transci.2016.10.018] [PMID]
  15. Gamonet C, Desmarets M, Mourey G, Biichle S, Aupet S, Laheurte C, et al. Processing methods and storage duration impact extracellular vesicle counts in red blood cell units. Blood Adv. 2020; 4(21): 5527-39.
    [    DOI:10.1182/bloodadvances.2020001658] [PMID] []
  16. Lang F, Gulbins E, Lerche H, Huber SM, Kempe DS, Föller M. Eryptosis, a window to systemic disease. Cellular Physiology and Biochemistry. 2008; 22(5-6): 373-80. [DOI:10.1159/000185448] [PMID]
  17. Saas P, Angelot F, Bardiaux L, Seilles E, Garnache-Ottou F, Perruche S. Phosphatidylserine-expressing cell by-products in transfusion: A pro-inflammatory or an anti-inflammatory effect? Transfusion clinique et biologique. 2012; 17-90: (3) 9. [DOI:10.1016/j.tracli.2012.02.002] [PMID]
  18. Hashemi Tayer A, Amirizadeh N, Mghsodlu M, Nikogoftar M, Deyhim MR, Ahmadinejad M. Evaluation of blood storage lesions in leuko- depleted red blood cell units. Iranian Journal of Pediatric Hematology and Oncology. 2017; 7(3): 171-9.
  19. Tissot J-D, Rubin O, Canellini G. Analysis and clinical relevance of microparticles from red blood cells. Current opinion in hematology. 2010; 17(6): 571-7. [DOI:10.1097/MOH.0b013e32833ec217] [PMID]
  20. Dinkla S, Peppelman M, Der RV, Atsma F, MJ NV, GJ VKM, et al. Phosphatidylserine exposure on stored red blood cells as a parameter for donor-dependent variation in product quality. Blood Transfus. 2014; 12(2): 204.
  21. Thangaraju K, Neerukonda S, Katneni U, W BP. Extracellular vesicles from red blood cells and their evolving roles in health, coagulopathy and therapy. Int J Mol Sci. 2021; 22(1): 153. [DOI:10.3390/ijms22010153] [PMID] []




A Comparative Study of Quality Metrics in Leukoreduced
Red Blood Cell Units Following Filtration with Two Distinct
Inline Filter Blood Bags

Fateme Roshanzamir1,2      , Sedigheh Amini-kafiabad3      , Javad Mohajer Ansari2      ,
Mahin Nikougoftar Zarif4      , Ali Arabkhazaeli5     , Mahshid Mohammadipour3

1Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
2Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
3Biological Products and Blood Safety Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
4Senior Assistant of the Center for Hematology and Regenerative Medicine, Karolinska Institute, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
5Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran

Received: 2025/12/10
Accepted: 2026/01/26
 





    http://dx.doi.org/10.61186/bloodj.22.1.11
    


Citation:
Roshanzamir F, Amini-kafiabad S, Mohajer Ansari J, Nikougoftar Zarif M, Arabkhazaeli A, Mohammadipour M. A Comparative Study of Quality Metrics in Leukoreduced Red Blood Cell Units Following Filtration with Two Distinct Inline Filter Blood Bags. J Iran Blood Transfus. 2025: 22 (4): 265-276
    
Correspondence: Roshanzamir F., Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences,
P.O.Box: 13885-79166, Bandar Abbas, Iran.
Tel: (+9876); 33333280
E-mail: fatemelab@gmail.com           

Correspondence: Amini Kafi-Abad S., Professor of Biological Products and Blood Safety Resaerch Center, High Institute for Research and Education in Transfusion Medicine.
P.O.Box: 14665-1157, Tehran, Iran.
Tel: (+9821) 88601573
E-mail: s.amini@
1- Acridine Orange
1- Biological safety cabinet
1- Platelet Concentrate
2- Food and Drug Administration
3- Normal Skin Flora
4- Platelet Rich Plasma-Platelet Concentrate
5- Eosin-Methylene blue
6- Thioglycolate
1- Acridine Orange
1- Biological safety cabinet
1- Platelet Concentrate
2- Food and Drug Administration
3- Normal Skin Flora
4- Platelet Rich Plasma-Platelet Concentrate
5- Eosin-Methylene blue
6- Thioglycolate
tmi.ac.ir  		 A B S T R A C T
Background and Objectives
Approximately 85-90 million red blood cell (RBC) components are transfused worldwide each year. Among these, leukoreduced RBC units particularly important for patients chronically need blood transfusion. Leukocyte filtration is commonly performed using two methods: whole-blood filtration (WBF) and red blood cell filtration (RCF). Given the potential impact of processing techniques on product quality, this study was designed to compare the effects of WBF and RCF on product quality indicators. In this study, an attempt has been made to eliminate background variables by equalizing conditions in order to focus on the effect of the filtration method.
Materials and Methods
Twelve whole blood units were divided into two equal parts, with each part filtered using WBF or RCF filters. Samples were taken on days 2, 14, 28, and 42 and they were measured for microvesicle (MVs) concentration, erythrocyte indices, free hemoglobin (Hb) levels, osmotic fragility (OFT), pH, and lactate dehydrogenase (LDH) levels. Data were analyzed using SPSS software, with two-group independent t-tests and ANOVA with repeated measures.
Results
Over storage time, both product groups showed a significant increase in microvesicle concentration, LDH, OFT, free hemoglobin, MCV, and hematocrit, alongside a decrease in pH. The differences between groups were statistically significant at some sampling intervals for microvesicle concentration, pH, LDH, free hemoglobin, and OFT (p< 0.05).
Conclusions 
Given the homogenization of conditions and the relative elimination of individual variables, it seems that the components prepared with the WBF method differ in quality from those prepared with the RCF method. However, despite the observed differences, the highest level of significance for the indicators was on the last day of storage period. These findings indicate that, both product groups remained within quality limits for transfusion.
Key words: Erythrocyte Transfusion, Blood Component Removal, Storage Lesions, Red Blood Cells, Cell-derived Microparticles, Cell Separation 

 
Copyright © 2025 Journal of Iranian Blood Transfusion, Published by Blood Transfusion Research Center.
This work is licensed under a Creative Common Attribution-Non Commercial 4.0 International license.



 
Type of Study: Research | Subject: Blood Transfusion
References
1. Rana M, Arfat Y, Naseem O, Mazari N, Manzoor N, Aziz RS, Rashid M, Mohsin S. Levels of red blood cells derived microparticles in stored erythrocyte concentrate. African Journal of Pharmacy and Pharmacology. 2020;14(6):185-91. [DOI:10.5897/AJPP2020.5126]
2. Nikulina M, Nemkov T, D'Alessandro A, Gaccione P, Yoshida T. A deep 96-well plate RBC storage platform for high-throughput screening of novel storage solutions. Front Physiol. 2022;13:1004936. [DOI:10.3389/fphys.2022.1004936] [PMID] []
3. World Health Organization. Global status report on blood safety and availability 2021. World Health Organization; 2022:1-51. [DOI:10.1007/978-3-030-05325-3_125-1]
4. Ma SR, Xia HF, Gong P, Yu ZL. Red blood cell-derived extracellular vesicles: An overview of current research progress, challenges, and opportunities. Biomedicines. 2023;11(10):2798. [DOI:10.3390/biomedicines11102798] [PMID] []
5. Westerman M, Porter JB. Red blood cell-derived microparticles: an overview. Blood Cells, Molecules, and Diseases. 2016; 59: 134-9. [DOI:10.1016/j.bcmd.2016.04.003] [PMID]
6. Levin G, Sukhareva E, Lavrentieva A. Impact of microparticles derived from erythrocytes on fibrinolysis. Journal of thrombosis and thrombolysis. 2016; 41(3): 452-8. [DOI:10.1007/s11239-015-1299-y] [PMID]
7. Jin Z, Yao S, Li L, Sun S, Zhou Y, Zhou J, Wang Z, Cui Z. Efficient leukocyte removal and enhanced biocompatibility using PVDF membranes prepared by vapor-induced phase separation. Chinese Journal of Chemical Engineering. 2025;89:1-12. [DOI:10.1016/j.cjche.2025.08.017]
8. Silva ND, Nogueira LD, Nukui Y, Almeida-Neto CD. The effect of the leukoreduction filtration moment on the clinical outcome of transfused patients: A retrospective cohort study. Clinics. 2025; 2;80:100633. [DOI:10.1016/j.clinsp.2025.100633] [PMID] []
9. Dejigov Monteiro da Silva N, Nukui Y, Takahashi J, de Almeida Lopes Monteiro da Cruz D, de Souza Nogueira L. Effect of post-storage filters vs. pre-storage filters for leukoreduction of blood components on clinical outcomes: a systematic review and meta-analysis. Systematic reviews. 2024;13(1):196. [DOI:10.1186/s13643-024-02615-z] [PMID] []
10. Yang J, Yang Y, Gao L, Jiang X, Sun J, Wang Z, Xie R. Adverse effects of microparticles on transfusion of stored red blood cell concentrates. Hematology, Transfusion and Cell Therapy. 2024;46:S48-56. [DOI:10.1016/j.htct.2024.01.007] [PMID] []
11. Almizraq RJ, Holovati JL, Acker JP. Characteristics of extracellular vesicles in red blood concentrates change with storage time and blood manufacturing method. Transfusion Medicine and Hemotherapy. 2018; 45(3): 185-193 [DOI:10.1159/000486137] [PMID] []
12. Gao Y, Lv L, Liu S, Ma G, Su Y. Elevated levels of thrombin‐generating microparticles in stored red blood cells. Vox sanguinis. 2013; 105(1): 11-7. [DOI:10.1111/vox.12014] [PMID]
13. Nguyen DB, Ly TBT, Wesseling MC, Hittinger M, Torge A, Devitt A, et al. Characterization of microvesicles released from human red blood cells. Cellular Physiology and Biochemistry. 2016; 38(3): 1085-99. [DOI:10.1159/000443059] [PMID]
14. Xie R, Jia D, Gao C, Zhou J, Sui H, Wei X, et al. Homocysteine induces procoagulant activity of red blood cells via phosphatidylserine exposure and microparticles generation. Amino Acids. 2014; 46(8): 1997-2004. [DOI:10.1007/s00726-014-1755-6] [PMID]
15. Sadeghi Neysiyani S, Amini-Kafiabad S, Hossieni E, Roshanzamir F. Activated Platelet and Platelet-Derived Microparticle Levels: A Comparative Study between Apheresis Platelet Concentrates and Pooled Platelet-Rich Plasma Platelet Concentrates. Indian Journal of Hematology and Blood Transfusion. 2026:42(1):222-228. [DOI:10.1007/s12288-025-01977-1] [PMID] []
16. Roshanzamir F, Amini-Kafiabad S, Zarif MN, Arabkhazaeli A, Mohammadipour M. The potential effect of leukocyte filtration methods on erythrocyte-derived microvesicles: One step forward. European Journal of Translational Myology. 2022;32(3):10708. [DOI:10.4081/ejtm.2022.10708] [PMID] []
17. Ghezelbash B, Azarkeivan A, Pourfathollah A, Deyhim M, Hajati E, Goodarzi A. Comparative evaluation of biochemical and hematological parameters of pre-storage leukoreduction during RBC storage. Int J Hematol Oncol Stem Cell Res. 2018; 12(1): 35.
18. Almizraq RJ, Norris PJ, Inglis H, Menocha S, Wirtz MR, Juffermans N, et al. Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity. Blood advances. 2018; 2(18): 2296-306. [DOI:10.1182/bloodadvances.2018021931] [PMID]
19. Almizraq R, Tchir JD, Holovati JL, Acker JP. Storage of red blood cells affects membrane composition, microvesiculation, and in vitro quality. Transfusion. 2013; 53(10): 2258-67. [DOI:10.1111/trf.12080] [PMID]
20. Bicalho B, Pereira A, Acker J. Buffy coat (top/bottom)‐and whole‐blood filtration (top/top)‐produced red cell concentrates differ in size of extracellular vesicles. Vox Sang. 2015; 109(3): 214-20. [DOI:10.1111/vox.12272] [PMID]
21. Hashemi Tayer A, Amirizadeh N, Ahmadinejad M, Nikougoftar M, Deyhim MR, Zolfaghari S. Procoagulant activity of red blood cell-derived microvesicles during red cell storage. Transfusion Medicine and Hemotherapy. 2019;46(4):224-30. [DOI:10.1159/000494367] [PMID] []
22. Rubin O, Crettaz D, Tissot J-D, Lion N. Microparticles in stored red blood cells: submicron clotting bombs? Blood transfusion. 2010; 8(Suppl 3): s31.
23. D'Alessandro A, Liumbruno G, Grazzini G, Zolla L. Red blood cell storage: the story so far. Blood Transfusion. 2010;8(2):82.
24. Almizraq RJ, Seghatchian J, Acker JP. Extracellular vesicles in transfusion-related immunomodulation and the role of blood component manufacturing. Transfusion and Apheresis Science. 2016; 55(3): 281-91. [DOI:10.1016/j.transci.2016.10.018] [PMID]
25. Gamonet C, Desmarets M, Mourey G, Biichle S, Aupet S, Laheurte C, et al. Processing methods and storage duration impact extracellular vesicle counts in red blood cell units. Blood Adv. 2020; 4(21): 5527-39. [DOI:10.1182/bloodadvances.2020001658] [PMID] []
26. Lang F, Gulbins E, Lerche H, Huber SM, Kempe DS, Föller M. Eryptosis, a window to systemic disease. Cellular Physiology and Biochemistry. 2008; 22(5-6): 373-80. [DOI:10.1159/000185448] [PMID]
27. Saas P, Angelot F, Bardiaux L, Seilles E, Garnache-Ottou F, Perruche S. Phosphatidylserine-expressing cell by-products in transfusion: A pro-inflammatory or an anti-inflammatory effect? Transfusion clinique et biologique. 2012; 17-90: (3) 9. [DOI:10.1016/j.tracli.2012.02.002] [PMID]
28. Hashemi Tayer A, Amirizadeh N, Mghsodlu M, Nikogoftar M, Deyhim MR, Ahmadinejad M. Evaluation of blood storage lesions in leuko- depleted red blood cell units. Iranian Journal of Pediatric Hematology and Oncology. 2017; 7(3): 171-9.
29. Tissot J-D, Rubin O, Canellini G. Analysis and clinical relevance of microparticles from red blood cells. Current opinion in hematology. 2010; 17(6): 571-7. [DOI:10.1097/MOH.0b013e32833ec217] [PMID]
30. Dinkla S, Peppelman M, Der RV, Atsma F, MJ NV, GJ VKM, et al. Phosphatidylserine exposure on stored red blood cells as a parameter for donor-dependent variation in product quality. Blood Transfus. 2014; 12(2): 204.
31. Thangaraju K, Neerukonda S, Katneni U, W BP. Extracellular vesicles from red blood cells and their evolving roles in health, coagulopathy and therapy. Int J Mol Sci. 2021; 22(1): 153. [DOI:10.3390/ijms22010153] [PMID] []
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