whole blood processing
Abstract Summaries
Unlocking the Potential of Blood
Table of Contents
Introduction 2
Blood Component Processing Systems
3
TACSI WB System Product Quality 3
reveos system product quality
4
Atreus System 3C Product Quality
5
Red Blood Cell Quality
5
Plasma Quality
6
Platelet Quality
6
Platelet Quality Using Atreus System Platelet Yield Index (PYI)
7
Atreus System 3C Pathogen Reduction Technology Compatibility
Atreus System 3C Process Optimization
11
Atreus System 2C+ Product Quality
12
Red Blood Cell Quality
12
Plasma Quality
13
Platelet Quality
13
Product Quality: Processed Same Day Versus Overnight Hold
13
Product Quality: Processed With or Without Active Cooling
14
Atreus System 2C+ Process Optimization
Platelet Processing Systems OrbiSac System Product Quality 1
9
15
17
17
In Vivo Platelet Quality
17
In Vitro Platelet Quality
17
OrbiSac System Pathogen Reduction Technology Compatibility
18
OrbiSac System Process Optimization
19
TACSI PL System Product Quality
21
TACSI PL System Pathogen Reduction Technology Compatibility
23
TACSI PL System Process Optimization
25
Introduction
Terumo BCT has written the enclosed abstract summaries to demonstrate the unique features and clinical utility of its products. The
summarized abstracts and articles do not encompass or represent all published information. Terumo BCT prepares abstract summaries
for convenience only. Please review the complete abstracts for full information. Terumo BCT may have supplied equipment, accessories
and/or funds to research organizations in support of some of the studies referenced in these abstracts.
The traditional process of blood component manufacturing is lengthy, complex and largely manual. Even when using semi-automated
equipment, a typical laboratory staff may perform up to 15 tasks by hand to produce blood component products from a whole blood (WB)
unit (Data on file, Terumo BCT).
One alternative approach, based on advances in industrial automation and “lean manufacturing” methods, became available to blood
centers with the advent of the Atreus® Whole Blood Processing System for two component (2C) processing and the OrbiSac system
for processing leukoreduced pooled platelet concentrate (PPC) products. With the introduction of the Atreus 3C protocols, the Atreus
system now provides all of the blood components that are possible to produce from whole blood.
Another approach using innovative automation was also developed in 2007 by Terumo, together with Hettich, allowing the operator
to obtain six leukoreduced PPCs in one TACSI run from a pool of buffy coats. It is called the TACSI® (Terumo Automated Centrifuge &
Separator Integration) System
These products are not available in all world markets.
Terumo BCT was established through the integration of CaridianBCT and Terumo Transfusion, following Terumo Corporation’s acquisition
of CaridianBCT in April 2011.
Atreus System
Through automation and integrated software process control, the Atreus system consolidates numerous manual steps into a single,
standardized WB manufacturing operation. Advantages to the blood center include: consistent, high-quality blood components; less
product variability; fewer production errors; higher WB unit throughput; more efficient staff utilization; and simplified staff training.
OrbiSac System
Likewise, the automated OrbiSac system replaces labor-intensive Buffy Coat (BC) pooling and filtration with an efficient and controlled
process to produce PPC products. Blood center benefits include: consistent, high-quality PPCs; increased staff productivity; and increased
platelet yield and recovery.
Blood centers can use the Atreus 2C+ and OrbiSac systems in tandem to automate their entire blood component manufacturing operation.
When combined, these two automated systems streamline the entire process of production to just eight steps (Data on file, Terumo BCT).
To further increase their efficiency, blood centers can also combine the Atreus system with a pathogen inactivation system such as the
Mirasol® Pathogen Reduction Technology System. This further advance in integration permits the blood center to improve both product
safety and product quality in a single blood component manufacturing process.
TACSI PL System
Like the OrbiSac system, the TACSI PL system replaces labor-intensive techniques with an efficient, standardized process to produce
leukoreduced PPCs from pooled BCs. The main difference is in the unique disposable processing kit and device design enables
simultaneous processing of six pooled BC units at the same time, making the TACSI PL system well-suited for blood centers that
manufacture large volumes of PPC product. Other TACSI PL system benefits include consistently high PPC quality, increased platelet
yield and recovery, and greater staff productivity.
The TACSI PL system can also be combined with a pathogen inactivation system due to its high recovery of platelets. Its pathogen
reduction compatibility permits greater integration of the TACSI PL system into blood center operations, enhancing both product safety
and product quality in a single blood component manufacturing process.
In This Book
This abstract summary book provides an overview of the published results from clinical evaluations of the Atreus, OrbiSac and
TACSI systems. These evaluations demonstrate the high quality of the blood component products obtained using these systems.
They also document the improved productivity and other process enhancements experienced by blood centers that have implemented
these systems.
2
Blood Component Processing Systems
TACSI WB System Product Quality
The new TACSI whole blood (WB) component processing system from Terumo BCT consists of a TACSI WB disposable kit and the
automated TACSI device that separates six WB units at a time. Through an automated process, the TACSI WB system produces three
WB-derived component products:
■■
Leukoreduced red cell concentrate (RCC) units
■■
Plasma units
■■
Buffy Coat (BC) units for pooling
The TACSI WB system has undergone two internal studies to validate system performance and product quality. (Bidet, et al., 2011, 2012).
In a 2011 study by Bidet, et al., 100 WB units were collected, stored, transferred into the TACSI WB kit, and inserted into the TACSI device
for automated component processing. The component products were then evaluated, with the following results:
■■
Plasma recovery was above 90%
■■
Leukoreduced RCCs conformed to EU standards in residual leukocytes, hemoglobin and hemolysis
■■
BC volumes were about 35 mL (± 5 mL)
■■
Average BC hematocrit was 40%
■■
Average platelet content in BC pools was 4.4 x 1011 (when stored up to 12 hours at room temperature) and 4.1 x 1011 (when stored two
hours at room temperature)
Timed observations confirmed that the TACSI WB system is capable of processing six WB units within 20 minutes.
In a more detailed follow-up study in 2012, Bidet, et al., used the TACSI WB system to produce components from 50 WB units. They
evaluated the overall features and benefits of a fully automated processing device, as well as the resulting BC characteristics, plasma
recovery and RC recovery. They reported the following mean values:
■■
BC volume: 31.7 mL (± 2.0)
■■
BC hematocrit: 33.4 % (± 5.3)
■■
Plasma recovery in BC: 91.1% (± 3.2)
■■
RC loss in BC: 10.6 mL (± 2.0)
■■
Plasma recovery: 86.8% (± 1.8)
■■
RC recovery: 93.7% (± 1.4)
References:
Bidet F, et al., “A Step Further in Innovation With the TACSI Whole Blood Platform: Internal Validation of Expected Features and Benefits of a Full
Automated Blood Component Processing Machine.” Vox Sanguinis 2012; 103 (Suppl. 1): 269.
Bidet F, et al., “Re-Inventing Blood Component Processing with TACSI Whole Blood: Internal Validation of a Complete New System.” Vox Sanguinis
2011; 101 (Suppl. 1): 153.
The TACSI whole blood system is in conformance with the Medical Device Directive and is available in select markets. However, it is not for sale in
the United States (U.S.).
3
Reveos automated blood processing System Product Quality
The new Reveos automated WB component processing system from Terumo BCT consists of a three-component disposable set and an
automated Reveos device that separates four WB units at a time. Through an automated process, the Reveos system produces three
WB-derived component products:
■■
RBCC units
■■
Plasma units
■■
Interim platelet units (IPU) for pooling with platelet additive solution (PAS) or plasma to provide platelet concentrate (PC)
The Reveos system also produces residual leukocyte units as a by-product.
Processing time and the in vitro quality of blood components produced by the Reveos system were evaluated in comparison to a blood
center’s historical data for standard centrifugation and semi-automated separation. The investigators reported that the Reveos system
processed component products “significantly faster” than the blood center’s existing methods. They also concluded that the blood
components produced by the Reveos system were of equivalent quality to those produced by the existing methods (Johnson, et al., 2012).
In this study, the RCC units were stored at 4°C and were tested multiple times during 42 days of storage. Plasma factor levels were tested
after the plasma units had thawed. The platelet units were tested on days 1, 2, 5 and 7 of storage at 22°C.
The key results of the study are summarized below:
RCC
plasma
pc
Volume
(mL)
Hb
(g/unit)
Hct
(L/L)
Volume
(mL)
Platelet Count
(109/L)
Volume
(mL)
Platelet Yield
(109/unit)
Existing
Methods
249.9 ± 1.8
46.6 ± 0.9
0.58 ± 0.01
281.9 ± 2.1
9.2 ± 2.2
299.7 ± 3.2
297.4 ± 11.7
Reveos
System
272.2 ± 4.3
47.8 ± 1.7
0.58 ± 0.01
279.9 ± 5.3
11.6 ± 2.9
298.6 ± 7.1
332.0 ± 30.0
Reference:
Johnson LN, et al., “Quality of Components Prepared Using the Reveos Automated Blood Processing System.” Vox Sanguinis 2012; 103
(Suppl. 1): 112.
PAS is not available in the United Stated (U.S.)
Residual leukocytes are not a recognized product in the U.S.
4
Atreus System 3C Product Quality
The three component (3C) protocol for use with the Atreus system was introduced in 2008. Through an automated process, the Atreus
3C protocol produces three whole blood-derived component products:
■■
Red blood cell (RBC) units
■■
Leukoreduced plasma units
■■
IPU
Leukoreduction of the RBC units is accomplished manually. It is also a simple manual process to rest, pool and filter the IPUs to yield a
leukoreduced PPCs.
Nine clinical evaluations of the Atreus 3C protocol under blood banking conditions have been published since 2009. These studies have
demonstrated both that the Atreus 3C-processed blood component products meet current quality standards and that their quality is
equivalent or superior to existing methods. The results of these studies are summarized below.
RBC Quality
Compared to Existing Standards
When compared to Council of Europe (CE) quality standards, 90 RBC units processed by the Atreus system for three components showed
an average hemoglobin content of 49.3 g/unit (± 7.1), meeting the CE specification of at least 40 g/unit (Grouzi, et al., 2010).
Another study showed that Atreus 3C-processed RBC units met CE standards for hemoglobin content, hematocrit and residual leukocytes.
The investigators observed that 100% of the Atreus 3C RBC units met the minimum CE standard for hemoglobin, compared to 94% of the
RBC units that were processed using a semi-automated system (Jurado, et al., 2012).
Atreus 3C RBC Units
Hb (g/unit)
Hct (%)
WBC (106/unit)
52.3 (± 5.4)
(N=50)
57.5 (± 3.2)
(N=50)
0.10 (± 0.09)
(N=35)
>40
50–70
<1
CE Standards
Compared to Existing Methods
Hemoglobin content showed clear improvement in RBC units processed using the Atreus 3C protocol, as compared to units processed by
a semi-automated component expression system (Larrea, et al., 2009).
Hb/Unit (g)
Avg
SD
Min
Max
N
Via Atreus 3C Protocol
54.9
± 5.4
45.7
64.1
20
Via Semi-Automated Process
47.5
± 5.8
37.8
64.5
120
In another comparison study with a semi-automated system, the hemoglobin content of Atreus 3C-processed RBC units was found to
be equivalent (Jurado, et al., 2010, 2012).
Hb/Unit (g)
N
Avg
SD
Via Atreus 3C Protocol
52.3
± 5.4
50
Via Semi-Automated Process
50.1
± 5.9
50
The number of RBC unit discards was also studied as a measure of product quality. During a six-month period, the investigators counted
the number of RBC units discarded for common production-related causes using the blood center’s existing semi-automated processing
system. The following year, after the center had implemented the automated Atreus system, RBC discards were counted again, for the
same time period and for the same causes. After Atreus 3C implementation, the overall number of RBC units discarded for productionrelated causes decreased by 46.3%. The greatest decreases were seen in the three most important causes: leakage, low volume and
stopped filtration (Maia, et al., 2011).
RBC Units Discarded
by Cause
5
Existing System
(Pre-Atreus 3C)
Atreus 3C System
Percent Decrease
Using Atreus 3C System
Leakage from bag
113
57
49.6%
Low volume
102
12
88.2%
Stopped filtration
43
17
60.5%
Plasma Quality
Compared to Existing Standards
A study comparing the characteristics of Atreus 3C-produced plasma to CE requirements found that the average level of residual
leukocytes in 90 units of plasma was 0.05 ± 0.07 x 106/unit, meeting the CE standard (Grouzi, et al., 2010).
Another study showed that Atreus 3C-produced plasma units met CE standards for Factor VIII, Factor II and residual leukocytes
(Jurado, et al., 2012).
Factor VIII (IU/dL)
Factor II (IU/dL)
WBC (106/L)
113.5 (± 30.1)
(N=30)
95.3 (± 9.4)
(N=30)
0 (± 0)
(N=18)
>70
>70
<1
Atreus 3C Plasma Units
CE Standards
Compared to Existing Methods
Platelet contamination and unit volume for Atreus 3C protocol-produced plasma were equivalent to values measured in plasma produced
by a semi-automated system (Larrea, et al., 2009).
Platelets in Plasma (109/L)
Avg
SD
Min
Max
N
Via Atreus 3C Protocol
54.9
± 5.4
45.7
64.1
20
Via Semi-Automated Process
47.5
± 5.8
37.8
64.5
120
Via Atreus 3C Protocol
266
± 17
243
296
10
Via Semi-Automated Process
281
± 14
256
309
21
Plasma Volume (mL)
Another study of plasma quality showed that levels of residual leukocytes were significantly lower (less than the detection limit of
the assay) in 18 units produced by the Atreus system for three components than in 18 others produced by a semi-automated system
(Jurado, et al., 2010, 2012).
A study comparing the characteristics of Atreus 3C-produced plasma to CE requirements found that the average level of residual
leukocytes in 90 units of plasma was 0.05 ± 0.07 x 106/unit, meeting the CE standard (Grouzi, et al., 2010).
Another study showed that Atreus 3C-produced plasma units met CE standards for Factor VIII, Factor II and residual leukocytes
(Jurado, et al., 2012).
Volume (mL)
Concentration (109/L)
Yield (109/Unit)
WBC (106/Unit)
284 (± 20)
(N=30)
1,214 (± 249)
(N=30)
344 (± 68)
(N=30)
0.02 (± 0.02)
(N=18)
>40 per 60 x 109 platelets
<1,500
240
<1
Atreus 3C Plasma
Units
CE Standards
Platelet Quality
Compared to Existing Methods
Platelet yields in Atreus 3C protocol pools were equivalent to those derived from the pooled platelet products of a semi-automated
system (Larrea, et al., 2009).
Platelet Yield (x109)
N
Avg
SD
Via Atreus 3C Protocol
329
± 50
30
Via Semi-Automated Process
321
± 52
30
A similar study showed that platelet yields in Atreus 3C pools were 12 percent higher than in pools derived from a semi-automated system
(Jurado, et al., 2010, 2012).
Avg
SD
N
Via Atreus 3C Protocol
344
± 68
30
Via Semi-Automated Process
311
± 47
31
Platelet Yield (x109)
6
In another study, leukoreduced platelet concentrate produced from pooled IPUs within two to eight hours after blood collection using
the Atreus 3C protocol showed a mean platelet yield of 386 (± 37)/x 109 pool on day three of storage, with residual leukocytes measuring
consistently less than 1 x 106/unit. Additionally, in vitro markers of platelet metabolic and cellular activity, including pH, lactate, adenosine
triphosphate (ATP), LDH and CD62P, were measured in Atreus 3C protocol-produced pools during seven days of storage. They were found
to be acceptable and within the ranges observed in platelets produced by existing methods (Gulliksson, et al., 2009).
In vitro parameters of cell quality were also found to be equivalent in a comparison between platelet concentrates stored in PAS for up to
seven days produced by the Atreus system for both three components and two components and OrbiSac systems (Galan, et al., 2010).
Platelet Quality Using Atreus System Platelet Yield Index (PYI)
A unique feature of the Atreus system’s 3C automated whole blood component expression process is that it can generate a descriptive
numerical value called the PYI for each IPU it produces. Blood center staff can use the PYI to predict the actual platelet content of IPUs,
enabling them to manage IPU pooling to achieve optimal yields of platelet concentrate. This information is not available with other
processing systems unless a cell count is done for each IPU, a practice not commonly done. For example, depending on their operations,
they may use the PYI to exclude lower-yield units from production or they may use it to select the right mix of higher- and lower-yield units
to pool.
In a study reported in 2009, a blood center measured the quality of platelets in two cohorts of IPU pools processed by different pooling
methods using the Atreus 3C protocol. Each pool consisted of four IPUs, approximately 25 mL in volume. In one cohort, the IPUs were
randomly selected for the pools. In the other cohort, the IPUs were selected using the Atreus system PYI feature. IPUs scoring relatively
low on the PYI were excluded, leaving only the higher-yield IPUs for pooling. In both cohorts, approximately 200 mL of platelet additive
solution was used for pooling and filtration. Both cohorts were also compared to a third cohort that underwent the blood center’s standard
BC processing method (Maia, 2009).
Platelet yield was 18% higher, variability was reduced by 46, and the amount of residual leukocytes was the lowest, when the Atreus
system PYI feature was used to select higher-yield IPU pools (Maia, 2009).
x109/Pool
SD
N
Atreus System Using PYI to
Select Higher-Yield IPU Pools
331
± 26
27
Atreus System Using Random
Selection of IPU Pools
281
± 48
27
Standard BC Process Using Random
Selection of Platelet Pools
284
± 48
57
% Pools <106 WBC
N
Atreus System Using PYI to
Select Higher-Yield IPU Pools
99.9%
27
Atreus System Using Random
Selection of IPU Pools
99.7%
27
Standard BC Process Using Random
Selection of Platelet Pools
98.8%
57
Platelet Yield
Residual Leukocytes
Another study measured platelet yield and in vitro markers of platelet quality in IPUs produced from fresh whole blood and from overnightstored whole blood. Both IPU cohorts were processed using the Atreus system for three components, including its PYI feature to estimate
platelet content in the IPUs. The study showed no significant differences between the fresh and overnight-stored IPU cohorts in their
platelet yield or in vitro characteristics (Sandgren, et al., 2010).
7
References:
Galan AM, et al., “In Vitro Platelet Quality of Platelet Concentrates Obtained With Two Generations of Automated Processing Devices and Stored
in PAS Solutions for Up to Seven Days.” Vox Sanguinis 2010; 99 (Suppl. 1): 195.
Grouzi E, et al., “Quality Analysis of Blood Components Obtained by the Atreus 3C System.” Vox Sanguinis 2010; 99 (Suppl. 1): 198.
Gullikson H, et al., “Platelets Prepared From Whole Blood Units Within 2-8 Hours After Blood Collection Using the Atreus System.” Transfusion
2009; 49 (Suppl.): 101A-102A.
Jurado M, et al., “Validation of the Automated Whole Blood Processing System Atreus 3C in a Routine Setting.” Vox Sanguinis 2010; 99 (Suppl. 1):
196.
Jurado M, et al., “Automated Processing of Whole Blood Units: Operational Value and In Vitro Quality of Final Blood Components.” Blood Transfus
2012; 10: 63-71.
Larrea L, et al., “Comparison of an Automated Whole Blood Manufacturing System With an Established Semi-Automated System.” Transfusion
2009: 49 (Suppl.): 110A.
Maia S, et al., “Optimization of Platelet Pool Content Using the Atreus System and the Platelet Yield Indicator.” Transfusion 2009; 49 (Suppl.): 99A.
Maia S, et al., “The Impact of the Implementation of Automated Whole Blood Processing System in Terms of Discarded Components.” Vox
Sanguinis 2011; 101 (Suppl. 1): 155.
Sandgren P, et al., “Storage of Platelet Concentrates Made of Fresh and Overnight-Stored Whole Blood Processed on the Novel Atreus 3C System:
In Vitro Study.” Vox Sanguinis 2010; 99 (Suppl. 1): 191.
The Atreus 3C (RBC, plasma and platelet) whole blood processing protocol, as well as the Atreus Platelet Pooling Kit, are in conformance with the
Medical Device Directive and are available in select markets. However, they are not for sale in the United States (U.S.).
Page 8 - PAS is not available in the U.S.
8
Atreus 3C System Pathogen Reduction Technology (PRT) Compatibility
Blood centers seeking increased operational efficiency are combining the Atreus system for three components with pathogen inactivation
systems designed to enhance the safety of the blood supply. Leukoreduced plasma units and IPUs are produced first, using the Atreus
system, and are then treated with a pathogen inactivation system. The result is a single, integrated manufacturing process to achieve
product safety and quality.
In general, pathogen inactivation systems reduce the infectious levels of pathogens that may be present in donated blood, resulting in a
reduced risk of disease transmission through transfusion. Two major types of these systems are currently in use.
Terumo BCT’s Mirasol system uses the unique properties of riboflavin (vitamin B2), a non-toxic, naturally-occurring compound, and a
specific spectrum of ultraviolet (UV) light to inactivate viruses, bacteria, parasites and white blood cells in collected platelets and plasma.
The Mirasol system renders a broad range of disease-causing agents less pathogenic, while maintaining the quality of the treated blood
components.
Terumo BCT received a CE mark for the Mirasol system in 2007 for treating platelets suspended in plasma. A CE mark was granted in 2008
for the treatment of fresh frozen plasma (FFP) and of plasma-reduced platelet concentrates that are subsequently stored in PAS.
The other pathogen inactivation system in current use is the Intercept Blood System. This system inactivates pathogens in collected
platelets and plasma by targeting the pathogen’s nucleic acids. The system employs a photo-active psoralen compound called amotosalen
HCI in conjunction with ultraviolet A (UVA) light to block replication of DNA and RNA in the pathogen.
Two studies published in 2010 report on blood component quality following implementation of a continuous manufacturing process
consisting of the Atreus system and a pathogen inactivation system. Acceptable in vitro quality was found in pathogen-inactivated
components for storage periods of up to five days (Maia, et al., 2010) and up to seven days (Castrillo, et al., 2010).
The results of these studies are summarized below.
Maia, et al. (2010), studied the in vitro cell quality of platelets in PPCs produced by the Atreus system and then pathogen-inactivated by
the Mirasol system for platelets in PAS. The PPCs were stored in SSP+ for up to eight days. Cell quality was evaluated by cell count, pH,
blood gases, swirl, glucose and lactate content. Cell quality, respiration and glucose levels in PPCs were found to remain adequate for up
to five days. It was noted that cell quality may decrease after five days of storage but that more clinical data is needed to correlate in vitro
parameters and clinical outcome.
Atreus 3C System
Average Platelet Yield
291 ± 32 x 109 per pool
Residual Leukocytes
<1 x 106 per unit
pH (22°C)
Day 5
7.18 ± 0.02
Day 8
7.04 ± 0.05
Glucose
Day 8
0.66 mmol/L
Swirl
Day 5
Score 2
Day 8
Score 1
Oxygen
Day 3
77 ± 20 mm Hg
Day 5
70 ± 21 mm Hg
Day 8
30 ± 20 mm Hg
(Maia S, et al., 2010)
9
Castrillo, et al. (2010), evaluated RCCs and PPCs produced by the Atreus system for three components and then pathogen-inactivated
using the Intercept system. The components were stored for nine days. The PPCs were suspended in additive solution. All components
were found to meet CE standards. In vitro biochemical and functional quality in PPCs remained acceptable for seven days.
Intercept System
Average RCC Volume
273 ± 21 mL
Hb
56.7 ± 7.2 g
Hct
61.8 ± 7.22 %
Average Plasma Volume
Residual Leukocytes
273 ± 18 mL per unit
<1 x 106 per unit
Platelet Content
Day 2
3.3 x 1011 per pool
pH (22°C)
Day 2
7.15 avg
Day 5
7.09 avg
Day 7
7.04 avg
Glucose
Day 2
6.7 mmol/L avg
Day 5
4.2 mmol/L avg
Day 7
2.3 mmol/L avg
Lactate
Day 2
4.3 mmol/L avg
Day 5
8.8 mmol/L avg
12.1 mmol/L avg
(Castrillo, et al., 2010)
References:
Castrillo A, et al., “Evaluation of Atreus 3C System and Its Performance on Platelet Pools for Pathogen Reduction Treatment.” Vox Sanguinis 2010;
99 (Suppl. 1): 196.
Maia S, et al., “In Vitro Cell Quality of Atreus 3C-Derived Platelet Concentrates Treated with the Mirasol Pathogen Reduction Technology System.”
Vox Sanguinis 2010; 99 (Suppl. 1): 245.
The Atreus 3C (RBC, plasma and platelet) whole blood processing protocol, as well as the Atreus Platelet Pooling Kit, are in conformance with the Medical
Device Directive and are available in select markets. However, they are not for sale in the United States (U.S.).
The Mirasol system is in conformance with the Medical Device Directive and is available in select markets. However, the Mirasol system is not for sale in
the United States (U.S.).
Intercept and the Intercept Blood System are trademarks of Cerus Corporation.
Intercept, PAS and SSP+ are not available in the United States (U.S.).
10
Atreus System 3C Process Optimization
The automated Atreus system, introduced in 2008, consists of a self-contained processing device combined with enhanced process
management software and an integrated collection/processing disposable set. The Atreus system for three components automates
six primary steps of WB component processing: balancing, centrifugation, expression, sealing, volume determination and procedure/
process data. Traditionally, these steps required blood center staff to perform numerous manipulations by hand.
Through automation, the Atreus system is designed to improve productivity by replacing the “ebb-and-flow” pattern of manual WB batch
processing with a smoother, more efficient single-piece workflow. The system’s design further optimizes WB component manufacturing
through its simplicity of operation, smaller physical footprint, and centralized process control and reporting.
In a 2010 study, a blood center measured the efficiency of the Atreus system under actual operating conditions, as compared to the
center’s current semi-automated WB processing method. Process mapping, time studies and workflow models were employed during
a period of five weeks of operational use to evaluate 14 parameters of component manufacturing. These parameters ranged from unit
processing time to physical processing space.
The study found that, compared to the existing WB processing method, the Atreus system increased overall WB unit throughput, reduced
staff training time, reduced processing time and eliminated manufacturing steps, and required less equipment and physical space. The
blood center’s assessment was that the Atreus system increased its productivity and simplified its operations (Jurado, et al., 2010).
The below table summarizes the results of this study:
Evaluated Parameter
Process Performance
Atreus 3C Difference
Current
Atreus System
Numerical
Percentage
Unit Processing Time
(minutes)
58.81
40.03
–18.97
–31.9%
Unit Throughput
(units/1 employee/shift)
76.1
94.6
+18.5
+24.3%
Number of Employees
14
8
–6
–42.9%
Weeks of Training
8
2
–6
–66.7%
Productivity
Staff and Training
Process
Number of Steps
39
24
–15
–38.5%
Number of Queues
12
10
–2
–16.7%
Number of Manual Tasks
35
21
–14
–40.0%
10.94
5.62
–5.32
–48.6%
Number of Inspections
8
6
–2
–25.05
Number of SOPs
16
13
–3
–18.8%
48
21
–27
–56.3%
105
41
–77
–61.0%
Total Manual Time
(minutes)
Quality Assurance
Equipment/Facilities
Pieces of Equipment
Processing Space (m )
2
References:
Jurado M, et al., “An Operational Comparison of the Atreus 3C Whole Blood System to Current Component Manufacturing Processes.” Vox
Sanguinis 2010; 99 (Suppl. 1): 101.
The Atreus 2C+ (RBC, plasma and Buffy Coat) and 3C (RBC, plasma and platelet) whole blood processing protocols, as well as the Atreus Platelet Pooling
Kit, are in conformance with the Medical Device Directive and are available in select markets. However, they are not for sale in the United States (U.S.).
11
Atreus System 2C+ Product Quality
The Atreus system for two components protocol became available to blood centers in 2006. Developed to work in synergy with the
OrbiSac system, the protocol produces three whole blood-derived component products:
■■
RBC units
■■
Leukoreduced plasma units
■■
BC platelet units
The BC units are then managed by the OrbiSac system that automatically produces a leukoreduced PPC. The RBC units are leukoreduced
using an integrated filter.
Nine studies since 2006 have clinically evaluated and reported the quality of blood components produced using the Atreus 2C+ protocol.
The studies demonstrated that these products meet current quality standards and equal the quality of products of existing manual or
semi-automated processing methods. The study results are summarized below.
RBC Quality
Compared to Existing Standards
Volume yield, hemoglobin content, hematocrit and residual leukocytes in Atreus 2C+ protocol-produced RBC units were found to comply
with regulatory requirements (Cid, et al., 2007 and Tardivel, et al., 2008).
Atreus 2C+
(N=41)
Requirement
(Spain)
Vol (mL)
Hb (g)
Hct (%)
WBC (x106)
Bags with >106
WBC (%)
237 (± 22)
46.1 (± 6.6)
54.8 (± 3.1)
0.05 (± 0.08)
0
NA
>40
50-70
<1
≤10
Vol (mL)
Hb (g)
Hct (%)
WBC (x106)
263
51
57
0.05
(Cid, et al., 2007)
Atreus 2C+
(N=30)
(Tardivel, et al., 2008)
In a validation study preceding implementation of the Atreus system for two components, the volume yield, average hemoglobin,
average hematocrit and residual leukocyte levels in 40 RBC units were found to be in compliance with the blood center’s quality criteria.
(Ambriz-Fernandez R, et al., 2010).
Vol (mL)
Hb (g)
Hct (%)
WBC (x106)
Day 0
309
63.2
62
0.07
Day 21
291
60.4
67
--
Day 42
278
56.6
67
--
Atreus 2C+
(N=41)
(Ambriz-Fernandez, et al., 2010)
Compared to Existing Methods
Hemoglobin content was equivalent upon collection, and in vitro parameters of cellular and metabolic activity were equivalent throughout
42 days of storage, when RBC units processed using the Atreus 2C+ protocol were compared to those that underwent standard processing
(Sward-Nilsson, et al., 2006).
Volume, hemoglobin and hematocrit were equivalent; ATP was higher; other in vitro markers were equivalent; and cellular contamination
was less, when measured at the beginning and end of storage, in RBC units processed using the Atreus 2C+ protocol, compared to units
processed by a standard centrifuge method (Lehmann, et al., 2008).
12
plasma Quality
Compared to Existing Standards
Plasma units produced using the Atreus 2C+ protocol were found to meet regulatory standards for volume, platelet content, residual
leukocytes and Factor VIII (Cid, et al., 2007 and Tardivel, et al., 2008).
Atreus 2C+
(N=41)
Requirement
(Spain)
Vol (mL)
WBC (/µL)
Platelets (x103/µL)
271 (± 21)
0.04 (± 0.07)
6.5 (± 4.4)
NA
<100
<50
Vol (mL)
WBC (x106)
FVIII (%)
263
0.045
89
(Cid, et al., 2007)
Atreus 2C+
(N=30)
(Tardivel, et al., 2008)
Coagulation factor values in plasma produced by the Atreus 2C+ system during a validation study preceding system implementation were
found to comply with the blood center’s quality criteria (Ambriz-Fernandez, et al., 2010).
Compared to Existing Methods
Unit volume, Factor VIII and residual cell contamination in fresh frozen plasma processed using the Atreus 2C+ protocol were equivalent
to values in units processed by the existing method (Lehmann, et al., 2008).
platelet Quality
Compared to Existing Standards
Volume, platelet yield and residual leukocytes in PPC units produced using the Atreus 2C+ protocol were shown to meet regulatory
requirements (Cid, et al., 2007).
Atreus 2C+
(N=15)
Requirement
(Spain)
Vol (mL)
Yield (x1011)
WBC (x106)
Bags with >106
WBC (%)
350 (± 12)
3.6 (± 0.5)
0.14 (± 0.13)
0
NA
>3
<106
10
(Cid, et al., 2007)
BCs produced from the Atreus 2C+ protocol exhibited a platelet recovery rate of >90 percent and met the blood center’s internal BC
specifications (Tardivel, et al., 2008).
Compared to Existing Methods
Volume, platelet yield and residual cell contamination in BC-derived, leukoreduced PPCs using the Atreus 2C+ protocol were equivalent
to values in like units processed using an existing method (Lehmann, et al., 2008).
Product Quality: Processed Same Day Versus After Overnight Hold
Two blood centers compared the in vitro parameters of blood component products processed from WB on the day of collection with
those processed from WB stored overnight, using the Atreus 2C+ protocol (Graminske, et al., 2006) (Sandgren, et al., 2007). In both
studies, the “same-day” WB cohort was processed within eight hours of collection. The “overnight-hold” cohort was stored 16 to 20 hours
(Graminske, et al., 2006) and 14 to 24 hours (Sandgren, et al., 2007) after collection before being processed.
In vitro measures of quality were comparable, with no significant differences, between RBC, plasma and PPCs that were processed the
“same day” and those that were processed following an “overnight hold,” when using the Atreus 2C+ protocol (Graminske, et al., 2006)
(Sandgren, et al., 2007). Whether processed from “same-day” or “overnight-hold” WB units, the resulting Atreus 2C+ products complied
with current in vivo standards and previously published quality data. This is true even though the “same-day” cohort showed a lower-yield
after processing than did the “overnight-hold” one (Sandgren, et al., 2007).
13
Product Quality: Processed With or Without Active Cooling
Thomas, et al. (2007), using the Atreus protocol for two components, examined the quality of blood components produced from WB that
were actively cooled with butanediol to 20 °C to 24 °C following collection, as compared to components produced from WB that were
held for 14 hours at 22 ± 2 °C without active cooling. The RBCs were measured for hemolysis, ATP, 2,3-diphosphoglycerate (2,3-DPG),
potassium, glucose and lactate throughout 42 days of storage. The BCs were held for three hours at ambient temperature on day one
before being measured for volume, platelet content, hematocrit and activation markers. Plasma was measured for volume, total protein
and cellular contamination on day one, with samples frozen to measure coagulation factors.
No clinically significant difference was found in the quality of RBCs, BCs and plasma manufactured using the Atreus protocol from WB
units that were stored overnight at ambient temperature with or without active cooling. These blood component products were shown
to meet quality specifications and to be suitable for therapeutic use.
Product Quality: Processed in 4-BC Pools versus 5-BC Pools
A study also looked at the quality of RBC and PPC units made using the Atreus 2C+ protocol when the Atreus system was adjusted to
process 4-BC pools as compared to the standard 5-BC pools.
Three combinations of fresh and/or stored WB and BCs were used in both the 4-BC and 5-BC study groups. In all study groups, the in
vitro parameters of the resulting blood products were found to be similar. However, in RBCs prepared by the Atreus system for 4-BC
pools, volume and hemoglobin were decreased compared to RBCs prepared for 5-BC pools. Platelets in PPCs made from fresh WB were
significantly fewer than in PPCs from stored WB. Platelet recovery improved in BCs stored before processing, but the resulting PPCs did
not consistently meet the regulatory requirement for platelet content. The authors state that for 4-BC pools, processing fresh WB may
lead to inadequate product quality, while in other processing conditions, more work is needed to improve platelet recovery (Thibault,
et al., 2009).
References:
Ambriz-Fernandez R, et al., “Automated Blood Collection Technology in Mexico.” Vox Sanguinis 2010; 99 (Suppl. 1): 169.
Cid J, et al., “Blood Component Preparation With the Atreus 2C+ System in Routine Use.” Vox Sanguinis 2007; 93 (Suppl. 1): 98-99.
Graminske S, et al., “Evaluation of RBC, Buffy Coat, and Plasma Products Obtained After Automated Separation of Whole Blood Units by the Atreus
System.” Transfusion 2006; 46 (Suppl.): 74A.
Lehmann C, et al., “Automated Whole Blood Processing With the Atreus 2C+ System Exceeds Conventional Preparation Method.” Transfusion
Medicine Hemotherapy 2008; 35 (Suppl. 1): 64.
Sandgren P, et al., “In Vitro Quality of Platelet Concentrates From Pooled Buffy-Coats Made of Fresh and Overnight Stored Whole Blood Processed
on the Novel Atreus 2C+ System.” Transfusion 2007; 47 (Suppl.): 3A-4A.
Tardivel R, et al., “Validation of the Atreus 2C+/2C- System (Gambro BCT) in the Blood Center of EFS Bretagne.” Vox Sanguinis 2008; 95
(Suppl. 1): 326.
Thibault L, et al., “Evaluation of the CaridianBCT Atreus Whole Blood Processing and OrbiSac Systems for Preparation of Platelet Concentrates
Made by Pooling Four Buffy Coats.” Transfusion 2009; 49, (Suppl. 3): 94A.
Thomas S, et al., “Quality of Blood Components Produced Using the Gambro BCT Atreus 2C+ System From Whole Blood Held With or Without
Active Cooling.” Transfusion Medicine 2007; 17: 33.
Sward-Nilsson AM, et al., “In Vitro Quality of Red Blood Cells Obtained After Automated Separation of Whole Blood by the Atreus 2C+ System and
Stored for 42 Days.” Vox Sanguinis 2006; 91 (Suppl. 3): 308.
The Atreus 2C+ (RBC, plasma and Buffy Coat) whole blood processing protocol, as well as the OrbiSac System and Atreus Platelet Pooling Kit, are in
conformance with the Medical Device Directive and are available in select markets. However, they are not for sale in the United States (U.S.).
14
Atreus System 2C+ Process Optimization
The automated Atreus system consists of a self-contained processing device integrated with enhanced process management software
and an integrated collection/processing disposable set. The Atreus system automates six primary steps of WB component processing:
balancing, centrifugation, expression, sealing, volume determination and procedure/process data. Traditionally, these steps required
blood center staff to perform numerous manipulations by hand.
Through automation, the Atreus system is designed to improve productivity by replacing the “ebb-and-flow” pattern of manual WB batch
processing with a smoother, more efficient single-piece workflow. The system’s design further optimizes WB component manufacturing
through its simplicity of operation, smaller physical footprint, and centralized process control and reporting. Automation is extended to
production of PPC products from BCs when the Atreus system is used in tandem with the OrbiSac system.
Blood centers evaluating the Atreus system have documented the productivity advantages of the system in studies published since 2007.
Based on system simulation or implementation, evaluators compared the Atreus system to their existing manual production methods.
They found that the Atreus system increases WB unit throughput (Chatelain, et al., 2007; Maia, 2007; Stefan, et al., 2007; Tiongson, et al.,
2007), reduces operator manual time (Tiongson, et al., 2007), reduces training time (Chatelain, et al., 2007; White, et al., 2008), reduces
space requirements (White, et al., 2008), reduces manufacturing errors (Miller, et al., 2007), simplifies quality assurance (QA) and quality
control (QC) oversight (White, et al., 2008) and provides cost-savings (Vaught, et al., 2007). Also, the Atreus and OrbiSac integrated
collection/processing disposable sets was found to be compatible with commonly used transfusion sets, further improving process
efficiency (Thibault, et al., 2010).
Key findings reported in the studies are summarized below:
15
■■
In unit throughput (number of units per hour per full-time equivalent (FTE), new staff at one blood center achieved 87 percent of
the current manual productivity level of fully competent staff after just four hours of training on the Atreus system. New staff was
projected to be able to exceed the current manual productivity of fully competent staff by 37 percent after two weeks of Atreus
system training. This represented a decrease in training time of 75 percent from the center’s current manual training period of eight
weeks (Chatelain, et al., 2007).
■■
Other blood centers found that staff using the Atreus system reduced the overall WB component processing time by 55 percent
(Maia, 2007), 14 percent (Stefan, et al., 2007) and 21 percent (Tiongson, et al., 2007), when comparing Atreus system throughput to
that of manual processing methods.
■■
Maia (2007) also observed that a single operator using three Atreus devices could process 126 WB units in one working shift, an
output that took two operators to achieve when using the manual method of eleven 30-minute cycles of centrifugation each.
■■
In addition to throughput improvement, Tiongson, et al., (2007) found a 6 percent reduction in the time spent by equipment
operators in manual manipulations when using the Atreus system.
■■
Evaluating the Atreus system in comparison to the blood center’s existing manual method, Vaught, et al., (2007) identified financial
benefits in the fact that the Atreus system does not require WB in-line filtration. The opportunities were described as two-fold:
□□
The center’s rate of short draws is 4 percent (5,680 units) annually. Based on this rate, and given a current cost-savings of
$14.90 USD per non-filter Atreus disposable set compared to a traditional bag with in-line filter, the center calculated that using the
Atreus system would save $85,000 USD per year in short-draw disposables costs.
□□
The center estimated that it loses approximately 25 mL of plasma in the in-line filter of a manual processing bag. Based on its
estimate of 110,000 WB units per year from which plasma is obtained and sold for fractionation, the center projected that in using
the Atreus system (which does not require in-line filtration) the blood center would retain an additional 2,750 L of plasma to sell,
resulting in additional annual revenue of at least $255,000 USD.
■■
Reviewing space requirements, White, et al., (2008) determined that the Atreus system would provide their facility the capacity to
process 70,000 WB units per year in a manufacturing area of 23.23 square meters (250 square feet), as compared to the 66,000 WB
units produced from the 44.59 square meters (480 square feet) of their current manual processing operation.
■■
Additional process optimization was projected by White, et al., (2008) in the areas of:
□□
QA (Atreus system automated, electronic records versus manual, paper records)
□□
Equipment QC (a single Atreus system automated process versus individual procedures for four centrifuges and two scales)
□□
QA review (Atreus system electronic exceptions reporting/electronic capture versus paper records post-WB processing)
□□
Process flow (Atreus system process electronically enforced versus SOP enforcement of manual process)
■■
In a virtual system evaluation using actual historical operational data, Miller, et al., (2007) projected that the Atreus 2C+ system
would reduce QC data entry points by 42 percent, information reports by 26 percent, improperly prepared units by 100 percent and
contaminated units by 80 percent.
■■
A study by Thibault, et al., (2010) of average spiking and un-spiking forces for three widely used transfusion sets and the Atreus and
OrbiSac integrated collection/processing disposable set showed no significant difference in forces between the sets, confirming the
compatibility of the Atreus and OrbiSac sets for use in the blood center’s WB processing operations.
References:
Chatelain G, et al., “Evaluating the Gambro® BCT ® Atreus to Simplify Disaster Recovery.” Transfusion 2007; 47 (Suppl.): 261A.
Maia V, “Improved Production Process Management (Atreus/OrbiSac) Porto Regional Blood Centre (CRSP).” Vox Sanguinis 2007; 93 (Suppl. 1): 105.
Miller KR, et al., “Reducing Component Manufacturing Errors through Automation.” Transfusion 2007; 47 (Suppl.): 271A.
Stefan M, et al., “Evaluation of the Atreus System in the Component Production Process.” Transfusion 2007; 47: (Suppl.): 255A.
Thibault L, et al., “Compatibility of Transfusion Sets with Component Bags from the Atreus/OrbiSac System.” Transfusion 2010; 50: (Suppl.): 77A.
Tiongson G, et al., “Comparing the Gambro BCT Atreus to Current Component Manufacturing Processes.” Transfusion 2007; 47 (Suppl.): 255A-256A.
Vaught HM, et al., “The Atreus System vs. Whole Blood In-Line Filtration: A Financial Comparison of Two Methods.” Transfusion 2007; 47
(Suppl.): 259A.
White A, et al., “Evaluating the Gambro BCT Atreus for Use at Multiple Manufacturing Sites to Minimize Disaster Impact.” Transfusion 2008; 48
(Suppl.): 274A-275A.
The Atreus 2C+ (RBC, plasma and Buffy Coat) and 3C (RBC, plasma and platelet) whole blood processing protocols, as well as the Atreus Platelet Pooling
Kit, are in conformance with the Medical Device Directive and are available in select markets. However, they are not for sale in the United States (U.S.).
16
Platelet Processing Systems
OrbiSac System Product Quality
The OrbiSac system produces leukocyte-reduced platelet concentrates from pools of up to six units of BC platelets. These BC platelets
come from WB units that were processed using either standard techniques or the Atreus system.
The quality of PPC produced by the OrbiSac system was clinically evaluated under blood banking conditions in eight studies published
since 2004. These studies demonstrated that OrbiSac system-produced PPCs are equivalent in quality to PPCs derived from manual BC
methods, in terms of both in vivo performance and the in vitro markers of function and efficacy measured during storage. The study
results are summarized below.
In Vivo Platelet Quality
The clinical outcome of PPCs from the OrbiSac system was compared to PPCs produced by a manual process. In the test group, 36 patients
received 219 transfusions of OrbiSac system PPCs. In the control group, 36 patients received 205 transfusions of manual-method PPCs.
Three parameters of clinical outcome were measured: one-hour count increment (1-h CI), one-hour corrected count increment (1-h CCI)
and transfusion interval (time between transfusions). Multiple regression analysis was used to examine the impact of 16 patient and PPC
variables on clinical outcome (Cid, et al., 2008, 2009).
Key study results:
■■
1-h CI was significantly higher in OrbiSac system-method PPCs than in manual-method PPCs (Cid, et al., 2008).
■■
Platelet yield was also higher in OrbiSac system-method PPCs. Because the higher 1-h CI measured in this group was related to the
higher yield, the difference in clinical outcome between the two methods was not statistically significant (Cid, et al., 2009).
■■
The difference in 1-h CI between OrbiSac system-method and manual-method PPCs was statistically significant in those patients
who received up to five transfusions (Cid, et al., 2009).
■■
Regression analysis identified the PPC processing method (OrbiSac system versus manual) as the most determinant variable of the
16 predictor variables on clinical outcome that were examined (Cid, et al., 2009).
Platelet recovery (in terms of CCI) and platelet transfusion yield were examined over a two-year period in 4,287 transfusions of OrbiSac
system-produced PPCs stored in PAS, apheresis platelets in PAS and apheresis platelets in plasma. These two parameters of transfusion
efficacy were found to be equivalent for all three platelet-processing methods, with CCI and platelet transfusion yield decreasing
throughout five days of storage regardless of method used (Tardivel, et al., 2008).
Croxon, et al., (2008) obtained post-transfusion clinical reports for 165 transfusions of OrbiSac system-produced PPCs. Next-day platelet
counts were reported to be within expected values and no adverse effects were identified.
In Vitro Platelet Quality
PPCs produced by the OrbiSac system and stored in PAS for seven days showed excellent platelet recovery from BC pools, as well as
excellent storage pH, platelet counts, cell morphology and CD62p expression (Croxon, et al., 2008).
Following seven days of storage, PPCs produced by the OrbiSac system and PCs produced by a standard manual procedure were measured
for platelet function and release of platelet-derived microparticles (PMP). The products of both methods were found equivalent in both
platelet function and PMP. In addition, the platelet yield per unit was found to be higher in OrbiSac system-produced PPCs (Radziwon,
et al., 2008).
In a study to validate the OrbiSac system when used with two different PAS media and with plasma, the in vitro characteristics of the PPCs
were measured during seven days of storage. Regardless of storage media used, the OrbiSac system-produced PPCs showed excellent
in vitro quality, demonstrating normal swirl and pH; high platelet yields and recovery; residual leukocytes within regulatory limits; and no
deterioration in any parameter during the storage period (Rombout, et al., 2004).
Tardivel, et al., (2007) found high reproducibility in platelet content and high quality in measures of mean volume, plasma ratio and
leukocyte content when they examined the in vitro characteristics of PPCs produced by the OrbiSac system.
Garcia-Bernardo, et al., (2010) measured volume, platelet count and residual leukocytes in PPCs processed from pooled BCs using the
OrbiSac system. They found the measured values to be in compliance with CE requirements and with requirements proposed for the
blood center itself, thereby validating the OrbiSac system for standardized PPC processing in the facility.
17
References:
Cid J, et al., “Clinical Effect of Transfusion of Pooled Platelet Concentrates Obtained by Manual Pooling or by Automated Pooling of Buffy
Coats—A Retrospective Analysis of Corrected Count Increment.” Vox Sanguinis 2008; 95 (Suppl. 1): 137.
Croxon H, et al., “Validation of Pooled, Buffy-Coat Derived, Leucodepleted Platelet Concentrates in Additive Solution Manufactured Using the
OrbiSac Platelet Processing System.” Transfusion Medicine 2008; 18 (Suppl. 2): 25.
Garcia-Bernardo M, et al., “Validation of the OrbiSac BC System in the Coimbra Regional Blood Center.” Vox Sanguinis 2010; 99 (Suppl. 1): 198.
Radziwon P, et al., “Comparative Study on the Effect of Production Method for Platelet Concentrates on the Release of Platelet-Derived
Microparticles and Platelet Function.” Vox Sanguinis 2008; 95 (Suppl. 1): 325.
Rombout E, et al., “Platelet Concentrates Produced by the OrbiSac BC System and Stored in Different Media.” Vox Sanguinis 2004; 87
(Suppl. 3): 71.
Tardivel R, et al., “Evaluation of the Efficacy of Platelet Transfusions.” Vox Sanguinis 2008; 95 (Suppl. 1): 326.
Tardivel R, et al., “OrbiSac BC System: An Automated System That Allows the Optimisation and Standardisation of the Production of Pooled
Platelet Concentrates.” Vox Sanguinis 2007; 93 (Suppl. 1): 110.
The Atreus 2C+ (RBC, plasma and Buffy Coat) whole blood processing protocol, as well as the OrbiSac System and Atreus Platelet Pooling Kit, are in
conformance with the Medical Device Directive and are available in select markets. However, they are not for sale in the United States (U.S.).
OrbiSac System PRT Compatibility
18
OrbiSac System PrT compatibility
For better operational efficiency, blood centers are combining the OrbiSac system with a pathogen inactivation system, such as the
Mirasol Pathogen Reduction Technology (PRT) System, designed to enhance the safety of the blood supply.
When these systems are combined, the OrbiSac system is used first to produce leukoreduced BC platelet concentrates suspended in
either 100% plasma or in PAS. Then the Mirasol PRT system is used to inactivate any leukocytes and pathogens in the BC platelets. The
result is a single, integrated manufacturing process that achieves both product quality and product safety.
The Mirasol PRT system uses the unique properties of riboflavin (vitamin B2), a non-toxic, naturally-occurring compound, and a specific
spectrum of UV light to inactivate viruses, bacteria, parasites and leukocytes in collected platelets and plasma. The Mirasol PRT system
renders a broad range of disease-causing agents less pathogenic, while maintaining the quality of the treated blood components.
Terumo BCT received a CE mark for the Mirasol PRT system in 2007 for treating platelets suspended in plasma. A CE mark was granted in
2008 for the treatment of FFP and of plasma-reduced platelet concentrates that are subsequently stored in PAS.
In a 2010 study by Maia, et al., a blood center reported on the in vitro quality of BC platelet concentrates suspended in PAS that were
produced using the OrbiSac system and subsequently pathogen-inactivated using the Mirasol PRT system. Parameters of in vitro quality
were measured during eight days of storage. The quality parameters measured were pH, swirl, lactate production, glucose consumption
and mean platelet volume (MPV).
The study found that OrbiSac-produced BC platelets in PAS that were pathogen-inactivated using the Mirasol PRT system retained
acceptable levels of in vitro quality for up to seven days of storage. The quality measured on days five and eight of the storage period
was found to be equivalent to that for platelets stored in 100% plasma. The authors cited their results as predictive of acceptable in vivo
survival and recovery.
Results for specific in vitro parameters were reported as follows:
19
■■
pH (@22 °C) was constant for days five and eight (day five: 7.11 ± 0.07; day eight: 7.08 ± 0.06).
■■
Swirls remained positive during storage.
■■
Lactate production on day five was 0.088 ± 0.030 mmol/1012 cells/h, and on day eight was 0.079 ± 0.024 mmol/1012 cells/h.
■■
Glucose consumption slightly decreased (day five: 0.049 ± 0.007 mmol/1012 cells/h; day eight: 0.041 ± 0.005 mmol/1012 cells/h).
■■
MPV slightly increased during storage.
References:
Maia S, et al., “Mirasol Pathogen Reduction Technology Treatment of OrbiSac Buffy Coat Platelets Suspended in Additive Solution.” Vox Sanguinis
2010; 99 (Suppl. 1): 245-246.
The Atreus 2C+ (RBC, Plasma and Buffy Coat) Whole Blood Processing System protocol, as well as the OrbiSac System and the Atreus Platelet Pooling
Kit, are in conformance with the Medical Device Directive and are available in select markets. However, they are not for sale in the United States (U.S.).
OrbiSac System PRT Compatibility
20
OrbiSac System Process Optimization
The OrbiSac system comprises a self-contained processing device that is integrated with enhanced process management software and
a special BC processing disposable set. The OrbiSac system consolidates six manual steps into a single automatic procedure to produce
leukoreduced PPC from up to six units of BC platelets. The six automated steps are BC pooling and rinsing; centrifugation; expression and
leukoreduction of the PPCs; and sealing of the PPC storage bags.
By automating BC platelet pooling and processing, the OrbiSac system is designed to streamline and standardize the operation, improve
process control and eliminate such variable manual factors as the handling of products between devices. OrbiSac system automation
has been shown to speed the platelet processing rate to up to 11 PPCs per hour per operator from sterile connection to sampling (Data
on file, Terumo BCT).
Blood centers evaluating the OrbiSac system have documented productivity gains in terms of high PPC platelet count (Castrillo, et al.,
2005; Espinosa, et al., 2004; Galuszka, et al., 2008; Gonzalez, et al., 2007; Larrea, et al., 2005; Salome, et al., 2008; Vignoli, et al., 2007), high
PPC platelet recovery (Castrillo, et al., 2005; Espinosa, et al., 2004; Vignoli, et al., 2007), reduced PPC preparation time (Vignoli, et al., 2007)
and reduced waste of platelet components (Garcia-Bernardo, et al., 2009).
The key findings of these studies are summarized below.
Platelet Yield (1011 platelets/unit)
Study
OrbiSac System
Manual Method
Percent Increase
Castrillo, et al., 2005
3.41
Espinosa, et al., 2004
3.07 (± 0.32)
2.60 (± 0.2)
18%
Gonzalez, et al., 2007
1
3.97 (± 0.61)
3.77 (± 0.55)2
3.72 (± 0.53)
3.51 (± 0.68)
7%
7%
Larrea, et al., 2005
3.37 (± 0.51)3
3.24 (± 0.63)4
30%5
Chicchi, et al., 2007
3.12 (± 0.46)6
3.00 (± 0.90)7
4%
Salome, et al., 2008
3.15 (± 0.47)
Vignoli, et al., 2007
4.10 (± 0.5)
Using Grifols blood bags
2
Using Macopharma blood bags
3
Four BCs per PPC
4
Five BCs per PPC
5
Expressed per BC, taking into account the five versus four BC differences
6
Five BCs per PPC
7
Six BCs per PPC
1
Regarding platelet count, the productivity advantage using the OrbiSac system reported in the above table from Larrea, et al., (2005)
was even greater than the PPC platelet counts alone indicate. The higher PPC platelet counts associated with the OrbiSac system were
obtained from pools of only four BC platelet containers, whereas the manual method’s lower PPC platelet counts came from pools of five
BC platelet containers.
Platelet Recovery (%)
Study
21
OrbiSac System
Castrillo, et al., 2005
85.12
Espinosa, et al., 2004
93 (± 9)
Vignoli, et al., 2007
76 (± 8)
Manual Method
Percent Increase
62 (± 2)
50%
Preparation Time
Evaluating additional aspects of productivity, Vignoli, et al., (2007) measured the preparation time using the OrbiSac system to be less
than 13 minutes per PPC and reported that OrbiSac system processing required fewer manual manipulations.
Reduction in Discarded Platelets
As a new quality indicator for their blood center, Garcia-Bernardo, et al., (2009) established a goal that the percentage of discarded platelet
components be reduced to ≤20 percent. Their study evaluated platelet discard rates for all four quarters of 2007, during which period the
existing PRP method was being progressively replaced by the BC method using the automated OrbiSac system; and for the first three
quarters of 2008, when all platelet processing was performed by the BC method using the OrbiSac system.
Garcia-Bernardo, et al. found that their platelet discard rates progressively decreased in all four quarters of 2007. In each of the first
three quarters of 2008, they met their quality goal of ≤20 percent of platelet components discarded. Their results are summarized in the
table below.
Time Period
Platelet Discard Rate
2007: OrbiSac System Progressively Replaces Existing PRP Method
1st Quarter
48.7%
2nd Quarter
46.1%
3rd Quarter
27%
4th Quarter
24.9%
2008: OrbiSac System Fully Replaces Existing PRP Method
1st Quarter
14.5%
2nd Quarter
17.8%
3rd Quarter
14.7%
References:
Castrillo Fernandez A, et al., “Use of OrbiSac System for the Preparation of Platelet Concentrates (PC).” Vox Sanguinis 2005; 89 (Suppl. 1): 170.
Chicchi R, et al., “The OrbiSac System: Results and Organizational Impact.” Blood Transfusion 2007; 5: 15-19.
Espinosa A and E Berg, “Evaluation of OrbiSac: An Automated System for Production of Buffy Coat Platelet Concentrates.” Vox Sanguinis 2004; 87
(Suppl. 3): 115-116.
Galuszka W, et al., “Comparative Evaluation of Leukoreduced Platelet Concentrates Produced With Either the OrbiSac BC System Method or
MCS+ Apheresis Method.” Vox Sanguinis 2008; 95 (Suppl. 1): 320.
Garcia-Bernardo L, et al., “Quality Indicator to Evaluate Implementation of the Buffy Coat Method for the Preparation of Pooled Platelet
Concentrates.” Vox Sanguinis 2009; 96 (Suppl. 1): 235-236.
González Fraile MI, et al., “Platelet Concentrates Obtained in a Blood Centre: A Two Year Analysis.” Vox Sanguinis 2007; 93 (Suppl. 1): 100-101.
Larrea L, et al., Letter to the Editor: “Fully Automated Processing of Buffy Coat-Derived Pooled Concentrates.” Transfusion 2005; 45 (4): 642-643.
Salome M, et al., “OrbiSac Platelet Concentrates: Analysis of Two Years of Routine Quality Data.” Transfusion 2008; 48 (Suppl.): 153A-154A.
Vignoli C, et al., “Implementation of the Automated OrbiSac BC System to Prepare Whole Blood Derived Platelet Concentrates at the EFS Alpes
Méditerranée Blood Center.” Vox Sanguinis 2007; 93 (Suppl. 1): 110.
The Atreus 2C+ (RBC, plasma and Buffy Coat) whole blood processing protocol, as well as the OrbiSac System and the Atreus Platelet Pooling Kit, are in
conformance with the Medical Device Directive and are available in select markets. However, they are not for sale in the United States (U.S.).
22
TACSI PL System Product Quality
The TACSI PL system enables laboratory staff to efficiently rinse and pool WB-derived BC units using a unique disposable processing kit
that connects to up to six bags of BC and one bag of PAS. The automated TACSI device then simultaneously centrifuges, separates and
leukoreduces up to six pooled BC units at a time to manufacture leukoreduced PPC products.
The quality of PPCs produced by the TACSI PL system has been clinically evaluated under blood banking conditions in six studies published
since 2008. The study results are summarized below.
Evaluations of In Vitro Platelet Quality
An evaluation was performed of 20 PPC units produced by the TACSI PL system from BCs that had been stored for six hours following
WB separation by existing means. The metabolic parameters of the produced PPCs were measured on the second, fifth and seventh
days of storage. The authors reported “optimal” values for these parameters, including a residual leukocyte count below 1 x 106 (Castrillo,
et al., 2008).
CD62 (%)
Glucose (mmol/L)
Lactate (mmol/L)
3
21.22 (± 5.25)
7.07 (± 0.74)
5.85 ( ± 0.54)
3
30.50 (± 5.32)
3
35.22 (± 4.34)
4.27 (± 1.07)
12.91 (± 4.27)
pH (22°)
Swirling
Day 2
7.38 (± 0.05)
Day 5
7.30 (± 0.19)
Day 7
7.26 (± 0.16)
Thirty PPC units produced using the TACSI PL system were tested through seven days of storage. Residual leukocytes on day 1 were
0.05 ± 0.10 x 106/unit. Other measured parameters showed platelet viability through day 7, with platelet activation on day 7 found to be
acceptable (Isola, et al., 2008).
pH
PF4 (ng/mL)
sGpV (ng/mL)
P-selectin
(ng/mL)
LDH
(U 37°C/L)
pO2 (mmHg)
pCO2 (mmHG)
Day 1
7.3 (± 0.06)
675 (± 366)
269 (± 81)
17.6 (± 4.1)
115 (± 13)
135.2 (± 11.1)
36.0 (± 2.3)
Day 5
7.3 (± 0.07)
8,878 (± 1771)
1,093 (± 310)
1,57.3 (± 34.0)
286 (± 82)
121.1 (± 7.8)
28.1 (± 2.3)
Day 7
7.3 (± 0.08)
10,922 (± 1590)
1,279 (± 407)
2,35.0 (± 55.2)
359 (± 124)
128.9 (± 9.8)
23.2 (± 2.6)
Comparisons with OrbiSac System
PPC units were produced from pooled BCs using both the TACSI PL and OrbiSac systems and measured through six days of storage in
PAS. In vitro quality was found to be generally similar in PPCs from both systems, with lower pH and CD62 seen in TACSI-produced PPCs
(Larrea, et al., 2008).
TACSI System (N=12)
pH (22°)
Orbisac System (N=12)
Swirling
Day 2
pH
7.0925
7.1950
CD62 (%)
32.9917
43.6833
Day 6
pH
CD62 (%)
7.1567
7.2769
42.7083
53.2583
In vitro markers of platelet quality were measured in PPC units prepared from pooled BCs from both the TACSI PL system and the OrbiSac
system, and stored up to seven days in PAS. Between the two PPC source systems, no statistically significant differences were found
in integral glycoproteins, activation-dependent antigens, bound von Willebrand factor and fibrinogen, and annexin V binding (Cid,
et al., 2008)
23
Comparison with Manual Method
One blood center measured the TACSI PL system against its previous manual method for producing PPCs from five BC units and PAS.
Platelet yields using the manual method had been about 3.9 x 1011. Platelet yields of TACSI-produced PPCs were measured at 4.9 x 1011.
The blood center also doubled its productivity using the TACSI PL system, reporting that one technician was able to manufacture 30 PPCs
a day (Salado, et al., 2010).
Platelet Yield
(1011 platelets/unit)
TACSI System PPCs (N = 62)
Manual Method PPCs (N = 118)
4.9
3.9
Evaluation Using New TACSI Cassette
In vitro quality was evaluated in PPCs produced from a TACSI PL system utilizing a new disposable processing kit that contained a cassette
designed to facilitate loading of pooled BCs into the TACSI device. Measured in vitro parameters of PPCs produced using this new kit design
were compared to those produced from existing methods and found to be within quality specifications with no significant differences
noted (Biset, et al., 2010).
References:
Biset R, et al., “Innovation in Blood Processing: Introduction of the First ‘Ready to Load’ Cassette for Platelet Pools Preparation on the Terumo
TACSI.” Vox Sanguinis 2010; 99 (Suppl. 1): 508.
Castrillo A, et al., “Evaluation of TACSI System to Obtain Platelet Concentrates (PC) and PC Metabolism Study.” Vox Sanguinis 2008; 95
(Suppl. 1): 317.
Cid J, et al., “Comparison of Two Semi-Automated Devices for Preparing Leukoreduced Pooled Buffy-Coat Derived Pooled Platelet Concentrates
in Additive Solution.” Vox Sanguinis 2008; 95 (Suppl. 1): 318.
Isola H, et al., “One Step Preparation of Leukoreduced Buffy Coat Derived Platelet Concentrates Using the Terumo Automated Centrifuge and
Separator Integration Device.” Transfusion 2008; 48 (Suppl): 64A.
Larrea L, et al., “Automated Processing of Buffy-Coat-Derived Pooled Concentrates, Evaluation of a New Device.” Transfusion 2008; 48
(Suppl): 148A.
Salado W, et al., “Pooled Platelet Concentrates With TACSI Terumo at EFS Centre-Atlantique.” Vox Sanguinis 2010; 99 (Suppl. 1): 206.
24
TACSI PL System Pathogen Reduction Technology Compatibility
Blood centers have begun to combine the TACSI PL system with a pathogen inactivation system to achieve a fully integrated manufacturing
process that improves both the quality and the safety of their platelet products.
Pathogen inactivation systems reduce the infectious levels of bacteria and viruses that may be present in donated blood, resulting in a
reduced risk of disease transmission through blood transfusion. There are three major types of these systems currently in use.
The Mirasol PRT system from Terumo BCT combines riboflavin (vitamin B2), a non-toxic, naturally occurring compound, with irradiation by
a specific spectrum of UV light to inactivate viruses, bacteria, parasites and white blood cells in collected platelets and plasma. The Mirasol
system renders a broad range of disease-causing agents less pathogenic, while maintaining the quality of the treated blood components.
Two other systems use other technologies. One system inactivates pathogens in collected platelets and plasma by targeting the
pathogen’s nucleic acids. It employs a photo-active psoralen compound called amotosalen HCI in conjunction with ultraviolet A (UVA)
irradiation to block replication of DNA and RNA in the pathogen. The other system inactivates pathogens in platelet concentrates using
shortwave ultraviolet (UVC) irradiation only, without addition of any photo-active agent.
Four studies published in 2010 and 2011 reported successful integration of the TACSI PL system with a pathogen inactivation system. The
results of these studies are summarized below.
A blood center implementing both the TACSI PL system and a pathogen-inactivation system to produce pathogen-inactivated PPC units
studied the resulting product quality and the impact on their production processes (Isola, et al., 2010).
Regarding product quality, Isola, et al., found that the mean values for volume, platelet content and residual plasma in TACSI-processed,
pathogen-inactivated PPC units met all of the requirements of the pathogen inactivation system.
Pathogen Inactivation System
Requirements
TACSI-Produced,
Pathogen-Inactivated PPCs
255–420
303 (± 16)
2–7
4.0 (± 0.7)
32–47
37 (± 1)
Volume (mL)
Platelet Content (10 )
11
Residual Plasma (%)
In addition, Isola, et al., studied the impact of integrating the pathogen inactivation system into their component manufacturing process.
They measured the amount of time and number of staff needed to produce 47 PPCs for pathogen-inactivation for each of two methods:
(1) their existing semi-automated production system using six pooled BCs, and (2) the automated TACSI production system using five
pooled BCs. For the TACSI method they also examined the impact of using one and two TACSI PL system devices.
They found that using the TACSI PL system improved their manufacturing productivity by reducing the time and staff needed to perform
equivalent operations to prepare PPCs for pathogen inactivation. Their results are summarized below.
Using Existing
System
Using TACSI,
1 Device
Using TACSI,
2 Devices
Reduction
Production Time
3.3 hr
3.2 hr
2.1 hr
0.1–1.2 hr
Technician Time
8.7 hr
6.1 hr
6.1 hr
2.6 hr
8
6
6
2
To Produce 47 PPCs
Technicians
A second study by Knutson, et al., reported on a blood center that had been using a pathogen-inactivation system to treat both BC-derived
platelets and apheresis-derived platelets. For greater cost-efficiency in treating the apheresis-derived platelets, the center had been using
one pathogen inactivation system kit to treat two doses of platelets from the same donor.
This blood center designed a study to test the feasibility of using one pathogen inactivation system kit to treat a double dose of PPCs
produced using the TACSI PL system. Forty-six PPC units were produced. Subtracting one bag lost to rupture, 45 PPC units were pathogeninactivated and stored for seven days. Pathogen inactivation was performed using a single kit, with the double dose divided into two bags.
Evaluating component quality, the blood center found that 87% of the stored PPC units had a platelet count of more than 300 x 109
(exceeding the local standard of 75%), and that all units had good swirling and detectable glucose on the seventh day of storage (Knutson,
et al., 2010).
25
In a third study, in vitro quality was evaluated in PPC units produced using the TACSI PL system and then treated with a pathogen
inactivation system. Two groups of 11 TACSI-PL produced PPCs were studied: one group receiving the pathogen inactivation treatment
and the other group not receiving treatment. Both groups were stored at 22 °C and in vitro tested on days 1, 2, 5 and 7 of storage.
No significant difference in platelet concentration was found between the two groups. The pathogen-inactivated group met all standards
for metabolic and functional parameters, as well as all pathogen inactivation system requirements. Platelet quality in the pathogeninactivated group was maintained through seven days of storage, with slight increases observed in metabolism and activation (Larrea,
et al., 2011).
A fourth study evaluated platelet recovery in 26 PPC units produced by the TACSI PL system and treated using a pathogen inactivation
system. The following results were reported:
■■
Volume (mL): 362 (±12)
■■
Platelet content (1011): 3.7 (± 0.5)
■■
Recovery (%): 92 (± 14)
In addition, no RC contamination was found and residual leukocytes were below 1 x 106. The authors concluded that the TACSI PL-produced,
pathogen-inactivated PPCs met their blood center’s standards (Castrillo Fernandez, et al., 2011).
References:
Castrillo Fernandez A, et al., “Recovery of Platelet Concentrate From Pooled Buffy Coats Prepared by New TACSI Device.” Vox Sanguinis 2011; 101
(Suppl. 1): 159.
Isola H, et al., “The Use of TACSI System: Effect of Automation on Routine Production of Pooled Platelet Concentrates for Pathogen Inactivation
in a French Regional Blood Center.” Vox Sanguinis 2010; 99 (Suppl. 1): 212-213.
Knutson F, et al., “A Feasibility Study with the TACSI Device Producing 2 Doses of Platelets Stored for 7 Days With the Use of One Intercept
Pathogen Inactivation Kit.” Vox Sanguinis 2010; 99 (Suppl. 1): 202.
Larrea L, et al., “In Vitro Evaluation of Platelets Treated With the THERAFLEX-UV Pathogen Reduction Technology.” Vox Sanguinis 2011; 101
(Suppl. 1): 181-182.
26
TACSI PL System Process Optimization
The TACSI PL system integrates a disposable processing kit with an automated device to manufacture leukoreduced PPC products from
BC source pools derived from whole blood. The TACSI processing kit is an integrated multi-bag assembly that permits up to six BC units
to be rinsed with additive solution and pooled. The pooled BC units are then loaded into the TACSI device for automated, simultaneous
centrifugation, separation and leukoreduction. The TACSI device can process six pooled BCs at a time within 15 minutes, for a total
production capacity of 24 leukoreduced PPCs per hour.
Through automation, the TACSI PL system enables a fast, standardized platelet production workflow. Because it reduces manual
operations, the TACSI PL system also reduces production errors and product loss. The high separation accuracy achieved by the TACSI
automatic device produces consistently high PPC yield and quality.
Blood centers evaluating the TACSI PL system have documented productivity gains in terms of high mean values for PPC platelet yield
(Castrillo, et al., 2008; Isola, et al., 2008; Jurado, et al., 2007; Larrea, et al., 2008; Vignoli, et al., 2010), PPC platelet count (Cid, et al, 2008) and
PPC platelet recovery (Biset, et al., 2010; Castrillo, et al., 2008; Jurado, et al., 2007; Larrea, et al., 2008). Studies have also reported increased
PPC product output with less time and staff (Biset, et al., 2010; Vignoli, et al., 2010).
The key findings of these studies are summarized below.
Platelet Yield (1011 platelets/unit)
Study
Castrillo, et al., 2008
Isola, et al., 2008
TACSI System
OrbiSac System
3.77 (±0.44)
4.6 (±0.8)
Jurado, et al., 2007
3.27 (±0.55)
Larrea, et al., 2008
3.18 (±0.28)
3.10 (±0.29)
Vignoli, et al., 2010
4.3 (±0.7)
4.0 (±0.6)
Platelet Count (109 platelets/unit)
Study
Cid, et al., 2008
TACSI System
OrbiSac System
1,105 (± 256)
1,181 (± 321)
TACSI System
OrbiSac System
Platelet Recovery (%)
Study
27
Biset, et al., 2010
>80
Castrillo, et al., 2008
>85
Jurado, et al., 2007
81
Larrea, et al., 2008
78.81 (± 5.11)
77.10 (± 3.95)
PPC Product Output
Two blood centers reported on their experience using the TACSI PL and OrbiSac systems for production of leukoreduced PPC products.
One center had produced more than 11,000 PPCs using the TACSI PL system. The other center had produced more than 7,000 PPCs
using the OrbiSac system. Each center analyzed its experience in order to evaluate the impact of the system on laboratory productivity.
In each blood center, whole blood was collected, stored and centrifuged to yield BC units. To produce leukoreduced PPCs from pooled
BCs, one center used two TACSI devices and the other center used two OrbiSac devices. In the center using the TACSI PL system, five BC
units and PAS were rinsed and pooled by means of the TACSI disposable processing kit. The pooled BCs were placed six at a time in each
automated TACSI device for centrifugation, separation and leukoreduction within a 12-minute period. In the center using the OrbiSac
system, six BC units and PAS were pooled by means of a traditional disposable product. The pooled BCs were placed one at a time in each
automated OrbiSac device for rinsing, centrifugation, separation and leukoreduction within a 15-minute period.
The blood center using the TACSI PL system (two TACSI devices) achieved a mean output of 47 PPCs, with a maximum output of 72 PPCs,
in a period of 2.1 hours and using 6.1 hours of equivalent staff time between two technicians. The center using the OrbiSac system (two
OrbiSac devices) achieved a mean output of 18 PPCs, with a maximum output of 25 PPCs, in 3.8 hours using only one technician. The
investigators concluded that both systems were adapted for small runs of PPC production but that the TACSI PL system was also suitable
for a larger PPC production volume (Vignoli, et al., 2010).
In another study, the ergonomic impact on PPC production of a design innovation in the TACSI disposable processing kit was evaluated.
A cassette had been added to the processing kit assembly, designed to make the kit containing the pooled BCs easier to load into the
TACSI device for processing. The investigators found that the new cassette reduced the kit loading time to less than 20 seconds (Biset,
et al., 2010).
References:
Biset R, et al., “Innovation in Blood Processing: Introduction of the First ‘Ready to Load’ Cassette for Platelet Pools Preparation on the Terumo
TACSI.” Vox Sanguinis 2010; 99 (Suppl. 1): 508.
Castrillo A, et al., “Evaluation of TACSI System to Obtain Platelet Concentrates (PC) and PC Metabolism Study.” Vox Sanguinis 2008; 95
(Suppl. 1): 317.
Cid J, et al., “Comparison of Two Semi-Automated Devices for Preparing Leukoreduced Pooled Buffy-Coat Derived Pooled Platelet Concentrates
in Additive Solution.” Vox Sanguinis 2008; 95 (Suppl. 1): 318.
Isola H, et al., “One Step Preparation of Leukoreduced Buffy Coat Derived Platelet Concentrates Using the Terumo Automated Centrifuge and
Separator Integration Device.” Transfusion 2008; 48 (Suppl): 153A.
Jurado MJ, et al., “Validation of the New Terumo Advanced Component Centrifuge with Separator Integrated of Platelets Concentrates From BC.”
Vox Sanguinis 2007; 93 (Suppl. 1): 101–102.
Larrea L, et al., “Automated Processing of Buffy-Coat-Derived Pooled Concentrates, Evaluation of a New Device.” Transfusion 2008; 48
(Suppl): 148A.
Vignoli C, et al., “Two Automatic Methods to Prepare Buffy-Coat Platelet Concentrates: OrbiSac and TACSI Impact on the Organization of
Production in Two French Regional Blood Centers.” Vox Sanguinis 2010; 99 (Suppl. 1): 200.
28
UNLOCKING THE POTENTIAL OF BLOOD
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