Utilization and quality of cryopreserved red blood cells in transfusion medicine

Henkelman, Sandra; Noorman, Femke; Badloe, John; Lagerberg, Johan W.M.

doi:10.1111/vox.12218

Cited by 42 publications

(56 citation statements)

References 96 publications

(123 reference statements)

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“…Frozen red cells are now generally accepted,[8, 20] and besides The Netherlands, also used by the US and Czech Republic military. [21, 22]…”

Section: Discussionmentioning

confidence: 99%

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Transfusion: -80°C Frozen Blood Products Are Safe and Effective in Military Casualty Care

Noorman¹,

Dongen²,

Plat

et al. 2016

PLoS ONE

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IntroductionThe Netherlands Armed Forces use -80°C frozen red blood cells (RBCs), plasma and platelets combined with regular liquid stored RBCs, for the treatment of (military) casualties in Medical Treatment Facilities abroad. Our objective was to assess and compare the use of -80°C frozen blood products in combination with the different transfusion protocols and their effect on the outcome of trauma casualties.Materials and MethodsHemovigilance and combat casualties data from Afghanistan 2006–2010 for 272 (military) trauma casualties with or without massive transfusions (MT: ≥6 RBC/24hr, N = 82 and non-MT: 1–5 RBC/24hr, N = 190) were analyzed retrospectively. In November 2007, a massive transfusion protocol (MTP; 4:3:1 RBC:Plasma:Platelets) for ATLS® class III/IV hemorrhage was introduced in military theatre. Blood product use, injury severity and mortality were assessed pre- and post-introduction of the MTP. Data were compared to civilian and military trauma studies to assess effectiveness of the frozen blood products and MTP.ResultsNo ABO incompatible blood products were transfused and only 1 mild transfusion reaction was observed with 3,060 transfused products. In hospital mortality decreased post-MTP for MT patients from 44% to 14% (P = 0.005) and for non-MT patients from 12.7% to 5.9% (P = 0.139). Average 24-hour RBC, plasma and platelet ratios were comparable and accompanying 24-hour mortality rates were low compared to studies that used similar numbers of liquid stored (and on site donated) blood products.ConclusionThis report describes for the first time that the combination of -80°C frozen platelets, plasma and red cells is safe and at least as effective as standard blood products in the treatment of (military) trauma casualties. Frozen blood can save the lives of casualties of armed conflict without the need for in-theatre blood collection. These results may also contribute to solutions for logistic problems in civilian blood supply in remote areas.

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“…Frozen red cells are now generally accepted,[8, 20] and besides The Netherlands, also used by the US and Czech Republic military. [21, 22]…”

Section: Discussionmentioning

confidence: 99%

“…In 2004 the NLAF MTFs (sea and land-based) became independent of regular ECs supply lines when the MBB implemented sterile processed -80°C Deep-frozen Erythrocyte Concentrates (DEC) that can be stored for 14 days after thaw and deglycerolization. [6–8]…”

Section: Introductionmentioning

confidence: 99%

Transfusion: -80°C Frozen Blood Products Are Safe and Effective in Military Casualty Care

Noorman¹,

Dongen²,

Plat

et al. 2016

PLoS ONE

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“…The mobile phase was 0.1 M sodium sulfate, 50 mM sodium acetate, 0.05% sodium azide, pH5, flow-rate was 0.5 ml/min, and the detection wavelength was 280nm. Thrombin generation assay (TGA) used Technothrombin fluorogenic substrate and RC High reagent (Technoclone, Vienna, Austria), and prekallikrein activator (PKA), plasmin, thrombin, thrombin-like amidolytic activities used S-2302, S-2251, S-2238, and S-2288 chromogenic protease substrates (Chromogenix, Milan, Italy), respectively [10]. Factor XI coagulant activity was measured by one-stage thromboplastin time coagulation assay with human factor XI—deficient and reference plasma (DiaMed, Cressier, Switzerland), and FXI/FXIa antigen with Human Factor XI quantitative sandwich ELISA (Abcam, Cambridge, UK) as before [10].…”

Section: Methodsmentioning

confidence: 99%

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

El‐Ekiaby¹,

Vargas

Moussa

et al. 2015

PLoS Negl Trop Dis

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BackgroundImmunoglobulin G (IgG) is an essential plasma-derived medicine that is lacking in developing countries. IgG shortages leave immunodeficient patients without treatment, exposing them to devastating recurrent infections from local pathogens. A simple and practical method for producing IgG from normal or convalescent plasma collected in developing countries is needed to provide better, faster access to IgG for patients in need.Methodology/Principal FindingsIgG was purified from 10 consecutive minipools of 20 plasma donations collected in Egypt using single-use equipment. Plasma donations in their collection bags were subjected to 5%-pH5.5 caprylic acid treatment for 90 min at 31°C, and centrifuged to remove the precipitate. Supernatants were pooled, then dialyzed and concentrated using a commercial disposable hemodialyzer. The final preparation was filtered online by gravity, aseptically dispensed into storage transfusion bags, and frozen at <-20°C. The resulting preparation had a mean protein content of 60.5 g/L, 90.2% immunoglobulins, including 83.2% IgG, 12.4% IgA, and 4.4% IgM, and residual albumin. There was fourfold to sixfold enrichment of anti-hepatitis B and anti-rubella antibodies. Analyses of aggregates (<3%), prekallicrein (5-7 IU/mL), plasmin (26.3 mU/mL), thrombin (2.5 mU/mL), thrombin-like activity (0.011 U/g), thrombin generation capacity (< 223 nM), and Factor XI (<0.01 U/mL) activity, Factor XI/XIa antigen (2.4 ng/g) endotoxin (<0.5 EU/mL), and general safety test in rats showed the in vitro safety profile. Viral validation revealed >5 logs reduction of HIV, BVDV, and PRV infectivity in less than 15 min of caprylic acid treatment.Conclusions/Significance90% pure, virally-inactivated immunoglobulins can be prepared from plasma minipools using simple disposable equipment and bag systems. This easy-to-implement process could be used to produce immunoglobulins from local plasma in developing countries to treat immunodeficient patients. It is also relevant for preparing hyperimmune IgG from convalescent plasma during infectious outbreaks such as the current Ebola virus episode.

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Section: Introductionmentioning

confidence: 99%

“…Cryopreservation (freezing) can extend RCC storage time to 10 years and beyond [1,2], and is predominantly used to preserve stocks of rare blood phenotypes, for storage for autologous and allogeneic use, and for military applications [3]. Cryopreservation is possible through the addition of high concentrations of glycerol, which acts as a cryoprotectant, to the RCC before freezing [3]. In North America, RCCs are commonly cryopreserved in 40% w/v glycerol concentrations with slow cooling rates ( 1 ° C/min) prior to storage at -65 ° C, while in Europe lower glycerol concentrations and rapid freezing are also used [4].…”

Section: Introductionmentioning

confidence: 99%

From Development to Implementation: Adjusting the Hematocrit of Deglycerolized Red Cell Concentrates to Meet Regulatory Standards

Turner

Hansen

Kurach

et al. 2016

Transfus Med Hemother

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Background: Before transfusion, thawed frozen red cell concentrates (RCCs) must be deglycerolized. In order to ensure that these products meet regulatory standards for hematocrit, an approach to manipulate hematocrit post deglycerolization was developed and implemented. Methods: Glycerolized and frozen RCCs were thawed and deglycerolized using the COBE 2991 cell processor, and the final product's hematocrit was adjusted by addition of various volumes of 0.9% saline / 0.2% dextrose. The in vitro quality of RCCs (hematocrit, hemolysis, hemoglobin content, volume, recovery, ATP, supernatant potassium, and others) were compared to Canadian Standards Association (CSA) and other standards for deglycerolized RCCs. Results: Addition of saline/dextrose re-suspension solution in a range of 65-90 g post deglycerolization led to acceptable hematocrits. In the pilot study, this approach resulted in RCCs meeting all CSA standards for deglycerolized RCCs, with stimulation of RBC metabolism demonstrated by increased ATP concentration. In the validation phase, results were similar, although the CSA hemolysis standard was not met. Pre- and post-implementation data confirmed that manipulated RCCs met CSA hematocrit standards. Conclusion: This process was implemented at Canadian Blood Services to provide deglycerolized RCCs that meet the CSA hematocrit standard. However, pre- and post-implementation data reveal that this deglycerolization process is not sufficient to have RCCs consistently meet hemolysis standards.

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Utilization and quality of cryopreserved red blood cells in transfusion medicine

Cited by 42 publications

References 96 publications

Transfusion: -80°C Frozen Blood Products Are Safe and Effective in Military Casualty Care

Transfusion: -80°C Frozen Blood Products Are Safe and Effective in Military Casualty Care

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

From Development to Implementation: Adjusting the Hematocrit of Deglycerolized Red Cell Concentrates to Meet Regulatory Standards

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