Official Journal of the British Blood Transfusion Society
Transfusion Medicine
|
ORIGINAL ARTICLE
Preparation of red blood cell concentrates and plasma units from whole blood held overnight using a hollow-fibre separation system L. Johnson, M. Kwok & D. C. Marks Research and Development, Australian Red Cross Blood Service, Sydney, Australia Received 30 April 2014; accepted for publication 10 March 2015
SUMMARY
BACKGROUND
Background: The ErySep system represents an alternative to centrifuge-based whole blood (WB) separation, using gravity and filtration through hollow-fibres (0·2 μm pore size) to produce red blood cell (RBC) and plasma components. The aim of this study was to characterise the quality of ErySep RBC and plasma units compared with standard products from WB held overnight.
The separation of whole blood (WB) into its individual components facilitates optimal product storage and appropriate patient-specific therapy. In Australia, the standard technique for separation of WB into plasma and red blood cell (RBC) components is based on centrifugal force, followed by press-based separation (Greening et al., 2010). However, blood processing equipments, such as centrifuges and plasma extractors, are expensive, require significant space and a reliable electricity source. As such, the fractionation of WB via centrifugation may not be possible because of lack of infrastructure, especially in developing countries or in remote and military settings (Natukunda et al., 2010; Hakre et al., 2011). The ErySep blood component separation system (Lmb Technologie GmbH, Schwaig, Germany) represents an attractive alternative to current separation methods as it can be used without any additional consumables, processing equipment or electricity. Further, the system is sterile and closed to the environment and has a long shelf-life. The system consists of three blood bags (WB collection bag, plasma and red cell storage bags) with an integrated WB filter to remove leucocytes and platelets, and a hollow-fibre chamber that separates leucoreduced WB into RBC and plasma components. The plasma is separated from RBCs by gravity-fed passage through the tubular hollow-fibre membrane with a diameter 220 >40 0·50–0·70 0·70 IU mL−1 (equivalent to 70% activity; Council of Europe, 2008). Only eight (67%) of the
Transfusion Medicine, 2015, 25, 13–19
plasma units produced with the ErySep system had FVIII levels >0·70 IU mL−1 . Overnight storage of WB has been shown to reduce coagulation factor levels, particularly FVIII (Cardigan et al., 2011). The decreased levels of FVIII were likely attributable to processing with the ErySep system, rather than just the overnight hold, as all of the matched controls met this requirement. Consistent with these findings, Hornsey et al., reported 30% of units processed with a hollow-fibre system failed to meet this specification, despite using WB processed within 2 h of collection (Hornsey et al., 2005). It has previously been suggested that the hollow-fibre filters may result in selective removal of certain factors, including fibrinogen (Hornsey et al., 2005). In addition, leucoreduction using WB filters has been shown to variably affect coagulation factor content (Heiden et al., 2004; Kretzschmar et al., 2004; Alhumaidan et al., 2013). Additional studies should be carried out to determine whether the hollow-fibre filtration or the time between collection and processing was responsible for the drastic reduction in FV and FVIII, resulting in the prolongation of the APTT in the ErySep units. Although a fractional volume of saline was used to prime the ErySep system, it is unlikely that the changes in plasma proteins were due simply to this dilutional effect. Firstly, the magnitude of change was too great. Further, not all factors were reduced during ErySep processing. These results suggest that processing WB held overnight with the ErySep system is not optimal to produce plasma for clinical purposes, but improvements could be achieved by processing the WB within a shorter time frame from collection. Plasma is generally considered to be an acellular product. However, reports have demonstrated that plasma produced by centrifugation can contain sufficient residual cells (leucocytes, platelets and red cells) to cause febrile non-haemolytic transfusion reactions and alloimmunisation (both HLA and RBC; (Willis et al., 1998; Pandey & Vyas, 2012). Although cellular contamination in the control plasma units was below our institutions standard, the ErySep units contained significantly fewer cells, which is not surprising because of the filtration step. Further, the ErySep plasma contained fewer microparticles than the control group, which is consistent with the reduced cellular contamination. The number of microparticles present in control plasma were similar to what has recently been reported (Sparrow & Chan, 2012). As microparticles are increasingly being considered a key component in the haemostatic effect of blood components (Lawrie et al., 2008), their presence may be clinically relevant.
CONCLUSION The ErySep system was capable of producing a RBC and plasma unit from WB that was held overnight prior to processing, without centrifugation or the use of a semi-automated press. The ErySep RBCs contained sufficient Hb and had a similar metabolic rate to control components. However, the plasma quality of the ErySep units was significantly reduced compared with units processed by standard methods, with lower protein
© 2015 British Blood Transfusion Society
ErySep hollow-fibre separation system 19 and coagulation factor levels. Therefore, the ErySep system may not be suitable for optimal component production using WB that has been held overnight. However, if required, such as in an emergency or military situation, RBCs of sufficient quality could be prepared using the ErySep system.
ACKNOWLEDGMENTS The authors would like to thank Diana Vidovic for her technical assistance. We acknowledge that Australian governments fund the Australian Red Cross Blood Service to provide blood,
REFERENCES Alhumaidan, H.S., Cheves, T.A., Holme, S. & Sweeney, J.D. (2013) The effect of filtration on residual levels of coagulation factors in plasma. American Journal of Clinical Pathology, 139, 110–116. Almizraq, R., Tchir, J.D., Holovati, J.L. & Acker, J.P. (2013) Storage of red blood cells affects membrane composition, microvesiculation, and in vitro quality. Transfusion, 53, 2258–2267. Blajchman, M. (2006) The clinical benefits of the leukoreduction of blood products. Journal of Trauma, 60, S83–S90. Brune, T., Fill, S., Heim, G., Rabsilber, A., Wohlfarth, K. & Garritsen, H.S. (2007) Quality and stability of red cells derived from gravity-separated placental blood with a hollow-fiber system. Transfusion, 47, 2271–2275. Cardigan, R., Van der Meer, P.F., Pergande, C. et al. (2011) Coagulation factor content of plasma produced from whole blood stored for 24 hours at ambient temperature: results from an international multicenter BEST Collaborative study. Transfusion, 51, 50S–57S. Council of Europe (2008) Guide to the Preparation, Use and Quality Assurance of Blood Components. Council of Europe Press, Strasbourg. Dijkstra-Tiekstra, M.J., van der, Meer, P.F., Cardigan, R., Devine, D., Prowse, C., Sandgren, P. & de, Wildt-Eggen, J. (2011) Platelet concentrates from fresh or overnight-stored blood, an international study. Transfusion, 51, 38S–44S. Greening, D.W., Glenister, K.M., Sparrow, R.L. & Simpson, R.J. (2010) International blood collection and storage: clinical use of blood products. Journal of Proteomics, 73, 386–395. Hakre, S., Peel, S.A., O’Connell, R.J. et al. (2011) Transfusion-transmissible viral
© 2015 British Blood Transfusion Society
blood products and services to the Australian community. L. J. assisted with the design of the research study, performed the research, analysed the data and wrote the manuscript. M. K. performed the research, analysed the data and critically reviewed the manuscript. D. M. designed the research study, performed statistical analysis and critically reviewed the manuscript.
CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.
infections among US military recipients of whole blood and platelets during Operation Enduring Freedom and Operation Iraqi Freedom. Transfusion, 51, 473–485. Heaton, W.A. (1992) Evaluation of posttransfusion recovery and survival of transfused red cells. Transfusion Medicine Reviews, 6, 153–169. Heiden, M., Salge, U., Henschler, R., Pfeiffer, H.U., Volkers, P., Hesse, J., Sireis, W. & Seitz, R. (2004) Plasma quality after whole-blood filtration depends on storage temperature and filter type. Transfusion Medicine, 14, 297–304. Hornsey, V.S., McColl, K., Drummond, O. & Prowse, C.V. (2005) Separation of whole blood into plasma and red cells by using a hollow-fibre filtration system. Vox Sanguinis, 89, 81–85. Johnson, L., Winter, K.M., Kwok, M., Reid, S. & Marks, D.C. (2013) Evaluation of the quality of blood components prepared using the Reveos automated blood processing system. Vox Sanguinis, 105, 225–235. Kretzschmar, E., Kruse, F., Greiss, O., Paunovic, D., Kallweit, T. & Trobisch, H. (2004) Effects of extended storage of whole blood before leucocyte depletion on coagulation factors in plasma. Vox Sanguinis, 87, 156–164. Lawrie, A.S., Harrison, P., Cardigan, R.A. & Mackie, I.J. (2008) The characterization and impact of microparticles on haemostasis within fresh-frozen plasma. Vox Sanguinis, 95, 197–204. Lu, F.Q., Kang, W., Peng, Y. & Wang, W.M. (2011) Characterization of blood components separated from donated whole blood after an overnight holding at room temperature with the buffy coat method. Transfusion, 51, 2199–2207. Marta, M., Rodriguez-Segura, E., Azqueta, C. et al. (2009) Cord blood separation with a
hollow-fiber system for obtaining fetal erythrocytes. Preliminary results. Vox Sanguinis, 99, 91–516. Moroff, G., AuBuchon, J.P., Pickard, C., Whitley, P.H., Heaton, W.A. & Holme, S. (2011) Evaluation of the properties of components prepared and stored after holding of whole blood units for 8 and 24 hours at ambient temperature. Transfusion, 51, 7S–14S. Natukunda, B., Schonewille, H. & Smit Sibinga, C.T. (2010) Assessment of the clinical transfusion practice at a regional referral hospital in Uganda. Transfusion Medicine, 20, 134–139. Orlov, D. & Karkouti, K. (2015) The pathophysiology and consequences of red blood cell storage. Anaesthesia, 70, 29–37. Pandey, S. & Vyas, G.N. (2012) Adverse effects of plasma transfusion. Transfusion, 52, 65S–79S. Sparrow, R.L. & Chan, K.S.-K. (2012) Microparticle content of plasma for transfusion is influenced by the whole blood hold conditions: pre-analytical considerations for proteomic investigations. Journal of Proteomics, 76, 211–219. Thomas, S., Beard, M., Garwood, M., Callaert, M., Waeg, G.V. & Cardigan, R. (2008) Blood components produced from whole blood using the Atreus processing system. Transfusion, 48, 2515–2524. Willis, J.I., Lown, J.A.G., Simpson, M.C. & Erber, W.N. (1998) White cells in fresh-frozen plasma: evaluation of a new white cell-reduction filter. Transfusion, 38, 645–649. Winter, K.M., Johnson, L., Kwok, M., Reid, S., Alarimi, Z., Wong, J.K., Dennington, P.M. & Marks, D.C. (2014) Understanding the effects of gamma-irradiation on potassium levels in red cell concentrates stored in SAG-M for neonatal red cell transfusion. Vox Sanguinis, 108, 141–150.
Transfusion Medicine, 2015, 25, 13–19
Copyright of Transfusion Medicine is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Transfusion Medicine
|
ORIGINAL ARTICLE
Preparation of red blood cell concentrates and plasma units from whole blood held overnight using a hollow-fibre separation system L. Johnson, M. Kwok & D. C. Marks Research and Development, Australian Red Cross Blood Service, Sydney, Australia Received 30 April 2014; accepted for publication 10 March 2015
SUMMARY
BACKGROUND
Background: The ErySep system represents an alternative to centrifuge-based whole blood (WB) separation, using gravity and filtration through hollow-fibres (0·2 μm pore size) to produce red blood cell (RBC) and plasma components. The aim of this study was to characterise the quality of ErySep RBC and plasma units compared with standard products from WB held overnight.
The separation of whole blood (WB) into its individual components facilitates optimal product storage and appropriate patient-specific therapy. In Australia, the standard technique for separation of WB into plasma and red blood cell (RBC) components is based on centrifugal force, followed by press-based separation (Greening et al., 2010). However, blood processing equipments, such as centrifuges and plasma extractors, are expensive, require significant space and a reliable electricity source. As such, the fractionation of WB via centrifugation may not be possible because of lack of infrastructure, especially in developing countries or in remote and military settings (Natukunda et al., 2010; Hakre et al., 2011). The ErySep blood component separation system (Lmb Technologie GmbH, Schwaig, Germany) represents an attractive alternative to current separation methods as it can be used without any additional consumables, processing equipment or electricity. Further, the system is sterile and closed to the environment and has a long shelf-life. The system consists of three blood bags (WB collection bag, plasma and red cell storage bags) with an integrated WB filter to remove leucocytes and platelets, and a hollow-fibre chamber that separates leucoreduced WB into RBC and plasma components. The plasma is separated from RBCs by gravity-fed passage through the tubular hollow-fibre membrane with a diameter 220 >40 0·50–0·70 0·70 IU mL−1 (equivalent to 70% activity; Council of Europe, 2008). Only eight (67%) of the
Transfusion Medicine, 2015, 25, 13–19
plasma units produced with the ErySep system had FVIII levels >0·70 IU mL−1 . Overnight storage of WB has been shown to reduce coagulation factor levels, particularly FVIII (Cardigan et al., 2011). The decreased levels of FVIII were likely attributable to processing with the ErySep system, rather than just the overnight hold, as all of the matched controls met this requirement. Consistent with these findings, Hornsey et al., reported 30% of units processed with a hollow-fibre system failed to meet this specification, despite using WB processed within 2 h of collection (Hornsey et al., 2005). It has previously been suggested that the hollow-fibre filters may result in selective removal of certain factors, including fibrinogen (Hornsey et al., 2005). In addition, leucoreduction using WB filters has been shown to variably affect coagulation factor content (Heiden et al., 2004; Kretzschmar et al., 2004; Alhumaidan et al., 2013). Additional studies should be carried out to determine whether the hollow-fibre filtration or the time between collection and processing was responsible for the drastic reduction in FV and FVIII, resulting in the prolongation of the APTT in the ErySep units. Although a fractional volume of saline was used to prime the ErySep system, it is unlikely that the changes in plasma proteins were due simply to this dilutional effect. Firstly, the magnitude of change was too great. Further, not all factors were reduced during ErySep processing. These results suggest that processing WB held overnight with the ErySep system is not optimal to produce plasma for clinical purposes, but improvements could be achieved by processing the WB within a shorter time frame from collection. Plasma is generally considered to be an acellular product. However, reports have demonstrated that plasma produced by centrifugation can contain sufficient residual cells (leucocytes, platelets and red cells) to cause febrile non-haemolytic transfusion reactions and alloimmunisation (both HLA and RBC; (Willis et al., 1998; Pandey & Vyas, 2012). Although cellular contamination in the control plasma units was below our institutions standard, the ErySep units contained significantly fewer cells, which is not surprising because of the filtration step. Further, the ErySep plasma contained fewer microparticles than the control group, which is consistent with the reduced cellular contamination. The number of microparticles present in control plasma were similar to what has recently been reported (Sparrow & Chan, 2012). As microparticles are increasingly being considered a key component in the haemostatic effect of blood components (Lawrie et al., 2008), their presence may be clinically relevant.
CONCLUSION The ErySep system was capable of producing a RBC and plasma unit from WB that was held overnight prior to processing, without centrifugation or the use of a semi-automated press. The ErySep RBCs contained sufficient Hb and had a similar metabolic rate to control components. However, the plasma quality of the ErySep units was significantly reduced compared with units processed by standard methods, with lower protein
© 2015 British Blood Transfusion Society
ErySep hollow-fibre separation system 19 and coagulation factor levels. Therefore, the ErySep system may not be suitable for optimal component production using WB that has been held overnight. However, if required, such as in an emergency or military situation, RBCs of sufficient quality could be prepared using the ErySep system.
ACKNOWLEDGMENTS The authors would like to thank Diana Vidovic for her technical assistance. We acknowledge that Australian governments fund the Australian Red Cross Blood Service to provide blood,
REFERENCES Alhumaidan, H.S., Cheves, T.A., Holme, S. & Sweeney, J.D. (2013) The effect of filtration on residual levels of coagulation factors in plasma. American Journal of Clinical Pathology, 139, 110–116. Almizraq, R., Tchir, J.D., Holovati, J.L. & Acker, J.P. (2013) Storage of red blood cells affects membrane composition, microvesiculation, and in vitro quality. Transfusion, 53, 2258–2267. Blajchman, M. (2006) The clinical benefits of the leukoreduction of blood products. Journal of Trauma, 60, S83–S90. Brune, T., Fill, S., Heim, G., Rabsilber, A., Wohlfarth, K. & Garritsen, H.S. (2007) Quality and stability of red cells derived from gravity-separated placental blood with a hollow-fiber system. Transfusion, 47, 2271–2275. Cardigan, R., Van der Meer, P.F., Pergande, C. et al. (2011) Coagulation factor content of plasma produced from whole blood stored for 24 hours at ambient temperature: results from an international multicenter BEST Collaborative study. Transfusion, 51, 50S–57S. Council of Europe (2008) Guide to the Preparation, Use and Quality Assurance of Blood Components. Council of Europe Press, Strasbourg. Dijkstra-Tiekstra, M.J., van der, Meer, P.F., Cardigan, R., Devine, D., Prowse, C., Sandgren, P. & de, Wildt-Eggen, J. (2011) Platelet concentrates from fresh or overnight-stored blood, an international study. Transfusion, 51, 38S–44S. Greening, D.W., Glenister, K.M., Sparrow, R.L. & Simpson, R.J. (2010) International blood collection and storage: clinical use of blood products. Journal of Proteomics, 73, 386–395. Hakre, S., Peel, S.A., O’Connell, R.J. et al. (2011) Transfusion-transmissible viral
© 2015 British Blood Transfusion Society
blood products and services to the Australian community. L. J. assisted with the design of the research study, performed the research, analysed the data and wrote the manuscript. M. K. performed the research, analysed the data and critically reviewed the manuscript. D. M. designed the research study, performed statistical analysis and critically reviewed the manuscript.
CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.
infections among US military recipients of whole blood and platelets during Operation Enduring Freedom and Operation Iraqi Freedom. Transfusion, 51, 473–485. Heaton, W.A. (1992) Evaluation of posttransfusion recovery and survival of transfused red cells. Transfusion Medicine Reviews, 6, 153–169. Heiden, M., Salge, U., Henschler, R., Pfeiffer, H.U., Volkers, P., Hesse, J., Sireis, W. & Seitz, R. (2004) Plasma quality after whole-blood filtration depends on storage temperature and filter type. Transfusion Medicine, 14, 297–304. Hornsey, V.S., McColl, K., Drummond, O. & Prowse, C.V. (2005) Separation of whole blood into plasma and red cells by using a hollow-fibre filtration system. Vox Sanguinis, 89, 81–85. Johnson, L., Winter, K.M., Kwok, M., Reid, S. & Marks, D.C. (2013) Evaluation of the quality of blood components prepared using the Reveos automated blood processing system. Vox Sanguinis, 105, 225–235. Kretzschmar, E., Kruse, F., Greiss, O., Paunovic, D., Kallweit, T. & Trobisch, H. (2004) Effects of extended storage of whole blood before leucocyte depletion on coagulation factors in plasma. Vox Sanguinis, 87, 156–164. Lawrie, A.S., Harrison, P., Cardigan, R.A. & Mackie, I.J. (2008) The characterization and impact of microparticles on haemostasis within fresh-frozen plasma. Vox Sanguinis, 95, 197–204. Lu, F.Q., Kang, W., Peng, Y. & Wang, W.M. (2011) Characterization of blood components separated from donated whole blood after an overnight holding at room temperature with the buffy coat method. Transfusion, 51, 2199–2207. Marta, M., Rodriguez-Segura, E., Azqueta, C. et al. (2009) Cord blood separation with a
hollow-fiber system for obtaining fetal erythrocytes. Preliminary results. Vox Sanguinis, 99, 91–516. Moroff, G., AuBuchon, J.P., Pickard, C., Whitley, P.H., Heaton, W.A. & Holme, S. (2011) Evaluation of the properties of components prepared and stored after holding of whole blood units for 8 and 24 hours at ambient temperature. Transfusion, 51, 7S–14S. Natukunda, B., Schonewille, H. & Smit Sibinga, C.T. (2010) Assessment of the clinical transfusion practice at a regional referral hospital in Uganda. Transfusion Medicine, 20, 134–139. Orlov, D. & Karkouti, K. (2015) The pathophysiology and consequences of red blood cell storage. Anaesthesia, 70, 29–37. Pandey, S. & Vyas, G.N. (2012) Adverse effects of plasma transfusion. Transfusion, 52, 65S–79S. Sparrow, R.L. & Chan, K.S.-K. (2012) Microparticle content of plasma for transfusion is influenced by the whole blood hold conditions: pre-analytical considerations for proteomic investigations. Journal of Proteomics, 76, 211–219. Thomas, S., Beard, M., Garwood, M., Callaert, M., Waeg, G.V. & Cardigan, R. (2008) Blood components produced from whole blood using the Atreus processing system. Transfusion, 48, 2515–2524. Willis, J.I., Lown, J.A.G., Simpson, M.C. & Erber, W.N. (1998) White cells in fresh-frozen plasma: evaluation of a new white cell-reduction filter. Transfusion, 38, 645–649. Winter, K.M., Johnson, L., Kwok, M., Reid, S., Alarimi, Z., Wong, J.K., Dennington, P.M. & Marks, D.C. (2014) Understanding the effects of gamma-irradiation on potassium levels in red cell concentrates stored in SAG-M for neonatal red cell transfusion. Vox Sanguinis, 108, 141–150.
Transfusion Medicine, 2015, 25, 13–19
Copyright of Transfusion Medicine is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
