C h a p t e r
9
Storage, Monitoring, Pretransfusion Processing, and Distribution of Blood Components 䊱 William B. Lockwood, PhD, MD; Jill Leonard, MT(AMT); and Sandy L. Liles, MT(ASCP)SBB
L O O D C O M P O N E N T manufacturing processes following collection have undergone marked changes in selected areas in the past few years and, yet, have remained relatively unchanged in other areas. New technology in automated component preparation, new regulatory and minimal acceptable final component requirements, and new computer capabilities have influenced the quality-oriented procedures that blood centers, blood banks, and transfusion services use in today’s manufacturing model. This model incorporates Food and Drug Administration (FDA) current good manufacturing practice (cGMP) regulations, originally published for drugs1 and revised to include biologics,2 from receipt to issue of the blood and blood component. The common thread that is found in cGMP and other regulatory bodies’ rules
B
(Clinical Laboratory Improvement Amendments; state laboratory statutes) or volunteer laboratory accrediting organization policies (College of American Pathologists; AABB; The Joint Commission; American Osteopathic Association) is maintaining the safety, quality, potency, purity, and identity of blood and blood components. The manufacturing facility demonstrates that it is following these concepts through the utilization of policies, processes, and procedures found in written standard operating procedures and associated records. Review of these documents assists these agencies, and the facility, in determining that cGMP compliance in storing, monitoring, pretransfusion processing, and distributing blood and blood components is achieved (see Chapter 3 for additional regulatory details).
William B. Lockwood, PhD, MD, Clinical Professor, Department of Pathology and Laboratory Medicine and Director, Transfusion Services and Tissue/Bone Bank, University of Louisville Hospital and NortonKosair Children’s Hospitals; Jill Leonard, MT(AMT), Administrative Supervisor, Clinical Laboratory, University of Louisville Hospital; and Sandy L. Liles, MT(ASCP)SBB, Technical Specialist, Transfusion Services, Norton Hospital, Louisville, Kentucky The authors have disclosed no conflicts of interest.
283 Copyright © 2008 by the AABB. All rights reserved.
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BL O O D A N D BL O O D C OM P O N E N T S T O R A G E Proper storage requirements must be followed on receipt of the blood or blood component from the collection area or blood supplier. Storage requirements and expiration dates vary depending on the particular blood unit as a result of the in-vitro cellular metabolism in storage medium or plasma protein stabilization (see Table 9-1). Failure to adhere to these storage and expiration requirements could result in decreased transfusion efficacy, potential harm to the recipient, or both. Temperature requirements during transport of blood or blood components differ from those of storage.4 Transport of whole blood and red cell components from the collection site to the processing facility is considered as short-term conditions, and use of validated transport containers (boxes, coolers) allows the temperature to be decreasing toward 10 C (providing that platelet concentrates will not be manufactured from a whole-blood unit, which would require the temperature to be cooling toward 20 C). However, should the red cell component require prolonged storage, the red cells must be maintained at 1 to 6 C. It is recommended that all red cell transport containers be validated to maintain a temperature of 1 to 6 C for a specified period to ensure compliance with the transport and storage requirements for Red Blood Cells (RBCs). Monitoring of Storage Temperatures Refrigerators, freezers, and platelet incubators for blood component storage are available with continuous temperature monitoring devices that would be able to detect a temperature deviation before blood components might be affected. Automated electronic monitoring devices that are available include but are not limited to the following: 1) a weekly pen and chart recorder, 2) a set of
hard-wired or radio frequency temperature recording devices, or 3) a centralized temperature monitoring system. Thermometers or thermocouplers are strategically placed in the equipment for optimal temperature monitoring. Daily checks of the temperature recordings should be performed to ensure proper operation of the equipment and recorder. Deviations from acceptable temperature ranges should be annotated on the temperature recording chart, as well as dated and initialed by the person noting the deviation. Most equipment also has audible alarms to alert personnel that temperature ranges are approachng unacceptable levels. Central alarm monitoring allows facilities that do not have personnel in the vicinity of the equipment to alert the designated staff at another location (or even send a page transmission to a selected individual) when an alarm is activated. Because platelets must be gently agitated during storage by the use of horizontal flatbed or elliptical rotators to prevent pH from decreasing below 6.2, alarm systems should also alert when the agitator has malfunctioned. If an automated temperature recording device is not used, then temperatures of the blood component storage environment must be measured manually every 4 hours.3(p18) This requirement includes ambient room temperature monitoring if blood components such as platelets are not stored in a platelet chamber or incubator. Transfusion services may elect to have blood storage refrigerators located in other areas of the hospital to allow immediate access to blood components in emergencies. Such a policy of having externally located refrigerators will require that the same blood monitoring standards are met. The best scenario would be to have transfusion service personnel responsible for monitoring these refrigerators. In the event that an equipment failure occurs and that the failure prevents acceptable
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TABLE 9-1. Storage and Expiration Requirements for Blood Components3(pp61-69) Component
Storage
Expiration
1-6 C. If intended for room temperature components, store at 1-6 C within 8 hours of collection
ACD/CPD/CP2D: 21 days
1-6 C
Original expiration or 28 days from date of irradiation, whichever is sooner
1-6 C
ACD/CPD/CP2D: 21 days
Whole Blood Requirements Whole Blood
Whole Blood Irradiated
CPDA-1: 35 days
Red Blood Cell Components Red Blood Cells (RBCs)
CPDA-1: 35 days Additive solution (AS-1, AS-3, AS-5): 42 days Open system: 24 hours RBCs Irradiated
1-6 C
Original expiration or 28 days from date of irradiation, whichever is sooner
RBCs Leukocytes Reduced
1-6 C
ACD/CPD/CP2D: 21 days CPDA-1: 35 days Additive solution (AS-1, AS-3, AS-5): 42 days Open system: 24 hours
Washed RBCs
1-6 C
24 hours
Apheresis RBCs
1-6 C
CPDA-1: 35 days Additive solution (AS-1, AS-3, AS-5): 42 days Open system: 24 hours
Apheresis RBCs Leukocytes Reduced
1-6 C
CPDA-1: 35 days Additive solution (AS-1, AS-3, AS-5): 42 days Open system: 24 hours
Frozen RBCs 40% glycerol or 20% glycerol
≤–65 C if 40% glycerol or as FDA approved; ≤ –120 C if 20% glycerol or as FDA approved
10 years; or a policy shall be developed if rare frozen units are to be retained beyond this time (see text for additional criteria).
Deglycerolized RBCs
1-6 C
Open system: 24 hours or as FDA approved Closed system: 14 days or as FDA approved (Continued)
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TABLE 9-1. Storage and Expiration Requirements for Blood Components3(pp61-69) (Continued) Component
Storage
Expiration
Rejuvenated RBCs
1-6 C
CPD/CPDA-1: 24 hours CPD/AS-1: freeze after rejuvenation at ≤ 42 days
Washed Rejuvenated RBCs
1-6 C
24 hours
Frozen Rejuvenated RBCs
≤–65 C
10 years AS-1: 3 years A policy shall be developed if rare frozen units are to be retained beyond this time.
Deglycerolized Rejuvenated RBCs
1-6 C
24 hours or as approved by FDA
Platelets
20-24 C with continuous gentle agitation
24 hours to 5 days depending on collection system
Platelets Irradiated
20-24 C with continuous gentle agitation
No change from original expiration date
Platelets Leukocytes Reduced
20-24 C with continuous gentle agitation
Open system: 4 hours
Pooled Platelets (open or closed system)
20-24 C with continuous gentle agitation
Open system: 4 hours
Pooled Platelets Leukocytes Reduced
20-24 C with continuous gentle agitation
Open system: 4 hours
Apheresis Platelets
20-24 C with continuous gentle agitation
24 hours to 5 days depending on collection system
Apheresis Platelets Irradiated
20-24 C with continuous gentle agitation
No change from original expiration date
Apheresis Platelets Leukocytes Reduced
20-24 C with continuous gentle agitation
Open system: 4 hours
Platelet Components*
Closed system: No change in expiration date
Closed system: Not in AABB Standards. Expiration date should be earliest expiration date in pool.
Closed system: 4 hours after pooling or 5 days following collection using an approved FDA system
Closed system: 5 days or 7 days if in an approved FDA-monitored program
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TABLE 9-1. Storage and Expiration Requirements for Blood Components3(pp61-69) (Continued) Component
Storage
Expiration
Apheresis Granulocytes
20-24 C without agitation
24 hours
Apheresis Granulocytes Irradiated
20-24 C without agitation
No change from original expiration date
Fresh Frozen Plasma (FFP)
≤ –18 C or ≤ –65 C
≤ –18 C: 12 months ≤ –65 C: 7 years†
FFP (after thawing)
1-6 C
24 hours
Plasma Frozen Within 24 Hours After Phlebotomy
≤ –18 C
12 months from original collection
Plasma Frozen Within 24 Hours After Phlebotomy (after thawing)
1-6 C
24 hours
Thawed Plasma
1-6 C
5 days from beginning of thawing of original unit
Apheresis FFP
≤ –18 C
12 months from original collection date
Thawed Apheresis FFP
1-6 C
24 hours
Liquid Plasma
1-6 C
5 days after expiration of RBCs
Cryoprecipitated AHF
≤ –18 C
12 months from original collection
Thawed Cryoprecipitated AHF
20-24 C
Open system or pooled: 4 hours
Plasma Cryoprecipitate Reduced
≤ –18 C
12 months from original collection
Plasma Cryoprecipitate Reduced (after thawing)
1-6 C
5 days
Recovered Plasma, liquid or frozen
Refer to short supply agreement in 21 CFR 601.22
Refer to short supply agreement in 21 CFR 601.22
Granulocyte Components*
Plasma Components
Single unit: 6 hours
*Platelet and granulocyte component storage temperatures presume that all reasonable steps are taken to maintain the temperature at 20-24 C as required by 21 CFR 600.15. † FDA approval is required to store longer than 12 months. AHF = antihemophilic factor; AS-1 = additive solution 1; AS-3 = additive solution 3; AS-5 = additive solution 5; CFR = Code of Federal Regulations; CPD = citrate-phosphate-dextrose; CPDA-1 = citrate-phosphate-dextrose-adenine-1; FDA = Food and Drug Administration; FFP = Fresh Frozen Plasma; RBC = Red Blood Cell.
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temperature ranges from being maintained, the facility should have policies, processes, and procedures in place to relocate the blood components. The secondary storage location may be another on-site refrigerator or freezer, validated storage boxes or coolers appropriate for the blood component and potential prolonged storage time, areas in which the ambient room temperature is monitored, or offsite locations. Because the safety, quality, purity, and potency of the blood components may be affected by delay in relocating to a secondary storage location, it is recommended that the relocation occur before the upper or lower acceptable storage temperature is exceeded. This precaution can be accomplished by setting the alarm points of the storage devices just short of the acceptable storage threshold. Some facilities may choose to use temperature-monitoring indicators applied to each blood component container. Such indicators (depending on the type of various temperature-sensitive labels available) typically monitor the liquid temperature of the immediate inner blood bag, not the liquid core temperature in the unit.5 However, a conservative approach is to use the indicator temperature in deciding component acceptability. The policies, processes, and procedures should specify how the facility will determine the disposition of these blood components. By following a blood banker’s philosophy of “when in doubt, throw it out,” noncompliance issues can be minimized. Biochemical Changes of Stored Blood Red Cells Because blood components are stored in plastic bags of different types and have a variety of added chemicals, the cellular and protein environment is modified from its natural state. Biochemical changes to red cells caused by “storage lesions” are one of the factors determining how long each component may
be stored. For RBC units, at least 75% of the transfused red cells must be present at 24 hours after transfusion.5 The biochemical parameters affected at different days of storage of nonleukocyte-reduced RBCs are shown in Table 9-2. Although the level of 2,3-diphosphoglycerate (2,3-DPG) is nearly absent at the end of storage times, the transfused red cell reestablishes normal levels within 12-24 hours following transfusion.6 Supernatant potassium levels are increased during storage, but because of the small plasma volume in the additive units, even most neonates can tolerate routine transfusion of 15 mL/kg without adverse events.7 Platelets Platelet biochemical changes relate to the production through glycolysis of lactic acid and carbon dioxide from oxidative metabolism of free fatty acids.8 With the advent of newer plastic bags for platelets, pH is maintained above 6.2 by allowing buffering of lactic acid by bicarbonate and diffusion of the carbon dioxide to the environment during agitation.8 Platelet shelf life is limited by functional changes during storage and the risk of bacterial growth. Bacterial contamination has been addressed by the requirement to monitor for the presence of bacterial organisms in platelet concentrates and apheresis platelets. All such components must be tested using various techniques to identify bacterial contamination.3(p13),9 An FDA program is under way at the time of this writing to allow storage of apheresis platelets for 7 days if collected by specific equipment and tested for bacterial contamination using FDA-approved instruments.10 Plasma Components FFP from whole-blood donation may be prepared from the primary centrifugation of whole blood into red cells and plasma or from platelet-rich plasma (PRP) following a hard
Copyright © 2008 by the AABB. All rights reserved.
CPD
Variable
Whole Blood
Whole Blood
Red Blood Cells
Whole Blood
Red Blood Cells
0
21.00
0
0
35.00
35.00
100.00
80.00
100.00
100.00
79.00
71.00
7.20
6.84
7.60
7.55
6.98
6.71
ATP (% of initial value)
100.00
86.00
100.00
100.00
56 (±16)
2,3-DPG (% of initial value)
100.00
44.00
100.00
100.00
<10.00
Plasma K+ (mmol/L)
3.90
21.00
4.20
5.10
27.30
78.50*
Plasma hemoglobin
17.00
191.00
82.00
78.00
461.00
658.00*
% Hemolysis
N/A
N/A
N/A
% Viable cells (24 hours posttransfusion) pH (measure at 37 C)
N/A
N/A
AS-1
AS-3
AS-5
Red Blood Cells
Red Blood Cells
Red Blood Cells
42.00
42.00
84.00
80.00
6.60
6.50
6.50
45 (±12)
60.00
59.00
68.50
<10.00
<5.00
<10.00
<5.00
50.00
46.00
45.60
N/A
42.00 76 (64-85)
N/A 0.50
386.00 0.90
N/A 0.60
*Values for plasma hemoglobin and potassium concentrations may appear somewhat high in 35-day stored RBC units; however, the total plasma in these units is only about 70 mL.
Blood Component Storage and Distribution
Days of Storage
CPDA-1
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TABLE 9-2. Biochemical Changes in Stored Nonleukocyte-Reduced Red Blood Cells3(p13)
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centrifugation (see Method 6-10). FFP prepared from whole blood donations may be frozen within: 1) 8 hours of whole blood collection (FFP) or 2) 24 hours of whole blood collection (Plasma Frozen Within 24 Hours After Phlebotomy, commonly referred to as FP24). FFP prepared from apheresis collection may be frozen within 6 hours of collection or according to device manufacturer’s instructions (also called FFP). The labile coagulation factors (Factor V and Factor VIII) as well as the stable factors are maintained well above 50% of donor levels in these frozen components.11 FFP (after thawing) prepared from apheresis collections expires 24 hours after thawing and may not be converted to Thawed Plasma. Thawed Plasma prepared from wholeblood-derived FFP expires as FFP (after thawing) 24 hours after thawing if stored at 1 to 6 C, and can be converted to Thawed Plasma. If FFP (after thawing) is converted to Thawed Plasma, the component label must be modified. Thawed Plasma expires 5 days after thawing if stored at 1 to 6 C.12 Thawed Plasma has a reduced concentration of Factor VIII, so it is not suitable for Factor VIII replacement when antihemophilic factor (AHF) derivatives are unavailable. Concentrations of remaining factors are clinically adequate for transfusion to other patients.11 By maintaining Thawed Plasma as part of a plasma inventory, a transfusion service can reduce wastage from unused FFP (after thawing). Blood centers have found it useful to prepare FP24 when operational logistics do not allow for plasma to be frozen in 6 to 8 hours in order to be labeled FFP. The use of FP24 by transfusing facilities may also increase their frozen plasma inventory. Cryoprecipitated AHF Cold precipitation at 1 to 6 C of insoluble glycoproteins in FFP produces Cryoprecipitated AHF (CRYO). After precipitation, the super-
natant fluid (cryoprecipitate-reduced plasma) is removed, leaving approximately 15 mL of CRYO, which is refrozen within 1 hour of preparation. CRYO contains ≥80 IU Factor VIII, >150 mg of fibrinogen, and most of the Factor XIII present in the donor plasma. Also present are von Willebrand factor multimers and fibronectin. After thawing, CRYO either is stored at 20 to 24 C or may be pooled using small quantities of 0.9% Sodium Chloride, Injection (USP) for flushing the bag into the final container. The supernatant fluid removed in the processing of CRYO is refrozen and labeled Plasma, Cryoprecipitate Reduced. This component has reduced levels of the precipitated glycoproteins but contains other enzymatic clotting proteins (Factors II, V, VII, IX, X, XI). This component has been mostly used as replacement fluid for thrombotic thrombocytopenia purpura (TTP) patients. Granulocytes Granulocytes are collected by apheresis techniques in the United States, although a buffy coat collection from a whole-blood donation may be useful for neonates. Minimal granulocyte yield of Apheresis Granulocytes should be ≥1 × 1010 but is difficult to achieve unless the donor has been pretreated with steroids, granulocyte colony-stimulating factors (GCSF), or both. Lower yield components are adequate for transfusion to neonates, who are becoming the major recipients of granulocytes. Granulocytes are fragile, deteriorate rapidly in vitro, must not be agitated during storage (granulocytes should never be stored in a refrigerated environment), and must not be leukocyte reduced. Therefore, granulocytes should be transfused as soon after collection as possible to gain increased clinical efficacy. Because of the requirement to transfuse granulocytes within 24 hours of collection, most blood centers maintain a list of donors who are willing to donate on an emergency basis
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Blood Component Storage and Distribution
and who have had negative infectious disease marker tests on multiple prior donations. PRE STO R A G E PRO CES SI N G Differential Centrifugation With the advent of plastic blood bags and the refrigerated centrifuge in blood component manufacturing in the early 1950s, separation of whole blood into various blood components became the norm. Depending on the “collection set” being used, blood centers can choose the set design required to meet the inventory requirements (doubles, triples, quads). Depending on the collection sets being used by the blood center, several methods of component preparation are available. Because of the physical properties of each cellular and liquid constituent in whole blood or blood components, separation has been achieved using differential centrifugation.13 Methods 8-4 and 8-5 describe the procedure for centrifuge calibration for platelet preparation, but each cellular or liquid constituent will require modifications of the procedure that are appropriate to manufacture each component. Quality control of the centrifuge should be monitored as part of the Quality Plan and Good Laboratory Practice (see Chapters 1, 3, and 6). Care should be used to properly pack and balance the centrifuge heads because of the bulky collection sets now being used. These sets may have an integral leukocyte reduction filter (or filters) and improper centrifugation may lead to less than optimal component separation or cause bag or tubing compromise. Also, an improperly balanced or packed centrifuge may pose not only safety concerns for the operator but also a potential to damage the centrifuge. Prestorage Filtration Leukocyte reduction with the use of blood filters may be performed either with integral fil-
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ters or by the use of sterile connection of the appropriate component filters to the selected component. Whole-blood filters currently allow recovery of leukocyte-reduced red cells and plasma with retention of platelets. The manufacturer’s directions must be followed as to timing and temperature of filtration for acceptable leukocyte reduction. Current practice is for the blood suppliers to leukocyte reduce the cellular component soon after collection and before storage (prestorage leukocyte reduction). This practice provides the best leukocyte reduction efficiency.14 Most automated collection devices have the capability for leukocyte reduction during the collection process. Computerized settings that conform to the manufacturer’s instructions must be programmed on the basis of each donor’s total blood volume, hematocrit, and platelet count. Quality control documentation of instrument settings, outcome measures, and adverse events is required. With proper operation techniques, a leukocytereduced cellular component having ≤105 white cells per collection can be achieved depending on the donor’s precollection white cell count. Freezing Acellular Components Plasma may be frozen by placing the product bag 1) in a dry ice-ethanol or dry ice-antifreeze bath, 2) between layers of dry ice, 3) in a blast freezer, or 4) in a mechanical freezer maintained at –65 C or colder. See Method 610 for preparation details. Freezing of cryoprecipitate should ideally occur within 1 hour of preparation. See Method 6-11 for a preparation procedure. Preparation of frozen cryoprecipitate-reduced plasma (which has been removed from the cryoprecipitate before freezing the CRYO) is performed the same as for FFP above. Several methods are available to determine whether the frozen plasma component may have inadvertently thawed during stor-
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age: 1) press a tube into the bag during freezing to leave an indentation that would disappear if the unit thaws (remove tube before storage); 2) place a rubber band around the liquid plasma bag and remove it after freezing to create an indentation that disappears with thawing; and 3) freeze the plasma bag in a flat, horizontal position but store it upright (air bubbles trapped along the bag’s uppermost broad surface during freezing will move to the top of the container should the unit thaw during storage).
creases the osmotic conditions, which allows a check for compatibility with the patient’s specimen before thawing and deglycerolizing the whole unit. Platelet freezing is still a research technique. Platelets are more susceptible to injury during cryopreservation than are red cells, but several techniques using dimethyl sulfoxide as the cryopreservative have been described.18
Freezing Cellular Components
Thawing FFP and Cryoprecipitated AHF
RBCs may be frozen for extended storage in the case of special needs (rare donor antigennegative units, autologous units), but loss of absolute red cell mass resulting from red cell damage will occur. Lysis of the red cells occurs both at freezing and at thawing because of the formation of ice crystals at freezing, unless a cryoprotective agent is used. Donor red cells may be screened for the presence of sickle cell trait depending on the donor population, and if positive, the cells are not usually frozen because of major cell loss when deglycerolized with hypertonic wash solutions.15 Cryoprotective agents such as glycerol have been used for many years to freeze RBCs. Several freezing methods are in use, but the two most commonly chosen are 1) high-glycerol, slow-freeze and 2) low-glycerol, fast-freeze.16 Most blood centers prefer the 40% wt/vol high-glycerol, slow-freeze technique (see Methods 6-7 and 6-8). Equipment is available to automate the procedure from glycerolization to deglycerolization, and modifications to the original procedure have been published.17 RBC units are usually placed in canisters to protect the polyolefin plastic bag during freezing, storage, and thawing. Several segments containing the glycerolized red cells should be frozen with the unit. These segments may be individually thawed using a deglycerolization procedure that gradually de-
FFP may be thawed at temperatures of 30 to 37 C or in an FDA-approved device. Thawing in a waterbath will require the container to be in a plastic overwrap before insertion into the water to prevent contamination of the container entry ports. There should be a procedure for quality control of indicated functions for any thawing device. Refer to Method 6-12 for thawing Cryoprecipitated AHF.
PO ST STOR A G E PRO CE S SI NG
Thawing and Deglycerolizing RBCs The freezing canister in which the RBC unit has been stored is placed in a 37 C dry heater or, after overwrapping, is placed in a 37 C waterbath. If the red cells have been frozen in the primary blood container, then the container should be thawed at 42 C.15 Thawing should be complete within 40 minutes. The glycerol cryopreservative must be removed before the component is transfused. This removal must be accomplished in a slow “deglycerolization” process to minimize hemolysis. Deglycerolization is performed using a stepwise decreasing osmolar solution of saline (see Method 6-7). Several vendors of deglycerolization instruments offer batch or continuous-flow washing techniques. Manufacturer’s instructions must be followed to ensure maximum red cell recovery and minimal hemolysis. Integrally attached tubing should be filled with the deglycerolized red cells and
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sealed appropriately so that a segment may be detached and available for crossmatch testing. The tubing must be labeled not only with the name of the collecting facility but also with the name of the deglycerolization facility (when different from the collecting facility). Shelf life of Deglycerolized RBCs will depend on the type of system used for deglycerolization. Closed-system devices allow storage for up to 14 days, but components prepared using open systems would expire within 24 hours of deglycerolization. Irradiating Cellular components are required to be irradiated for certain patient populations to prevent transfusion-associated graft-vs-host disease. Irradiation may be accomplished with the use of gamma irradiators (cesium-137 and cobalt60 radioisotopes), linear accelerators, ultraviolet-A irradiation (photoluminescence), and other nonradioisotope equipment (x-rays). The current gamma irradiation dose recommended to prevent proliferation of donor T lymphocytes in the recipient is a minimum of 25 Gy (2500 cGy/rads) to the central point of the blood container and 15 Gy (1500 cGy/ rads) to any other part of the container.3(p30) The expiration date of irradiated RBCs is 28 days after irradiation or the original expiration date, whichever date is earliest.3(p63) Confirmation that the blood container has received an adequate irradiation dose can be achieved with the use of commercially available radiographic film labels. A label may be affixed to the blood bag before irradiation and may be read following irradiation according to the manufacturer’s instructions. Alternately, a radiographic indicator label may be placed in the irradiator canister with the blood components and read after irradiating the single or multiple units. Several transfusion services have begun to universally irradiate platelets because platelets sustain minimal damage after irradiation and because the pos-
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sibility of not irradiating a component to be transfused to a patient in need of irradiated platelets is eliminated. Washing There are very few clinical indications for washing red cell or platelet components (multiple progressive allergic reactions, antibodies against immunoglobulin A (IgA) in the recipient when IgA-deficient cellular components are not available). Washing is accomplished with the use of 1 to 2 L of sterile normal saline (preferably using automated equipment). Up to 20% of the red cell yield or 33% of the platelet yield may be lost during the washing procedure. Because washing creates an “open system” and removes anticoagulant-preservative solutions, washed RBC units expire 24 hours after washing. Washed platelets expire 4 hours after washing. Pooling Pooling of certain blood components (wholeblood-derived platelets, red cells or washed red cells pooled with thawed FFP, and CRYO) may be required to provide clinically effective transfusion therapy without the need to transfuse multiple single components. Larger volumes of FFP for use as therapeutic plasma exchange fluid are best provided as “jumbo” plasma units (600 mL) rather than by means of pooling FFP units. Pooled platelets contain a significant number of red cells; therefore, units selected for the pool should be type-specific or type-compatible. A unique pool number should be affixed to the final container, and electronic or manual records must document all units included in the pool. If whole-bloodderived platelets are pooled using an open system, the expiration is 4 hours from the start of pooling with storage at 20-24 C. At the time of this writing, a commercial pooling bag is available, which allows for a bacteria detection procedure during the pooling pro-
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cess. The expiration date of this component is within 5 days of pooling when prepared in a closed system and in an FDA approved program. Reconstituted Whole Blood (thawed FFP pooled with RBCs or washed RBCs) expires with the earliest expiration of either of the two pooled components. Both of the unit numbers or a unique pool number should be affixed to the final container and electronic or manual records must document all units included in the pool. Reconstituted Whole Blood is stored at 1 to 6 C. Pooling of single cryoprecipitate components after thawing is accomplished in a similar manner as that used for platelets. A unique pool number should be affixed to the final container and electronic or manual records must document all units in the pool. The expiration date of pooled cryoprecipitate concentrates will depend on the method chosen for pooling. Open pooling systems have an expiration of 4 hours following pooling because the pooled component is stored at 20 to 24 C; thawed single and closed-systempooled cryoprecipitate concentrates should be transfused within 6 hours of thawing.
Aliquoting Certain transfusion recipients requiring verylow-volume transfusion (neonates) will require aliquoting small volumes (10-30 mL) into syringes from the original unit. Use of a sterile connection device and syringe set makes the process easy to perform (see Fig 9-1). A sterile connection device may also be used to “split” primary blood containers into smaller transfer bags for larger recipients to minimize TACO. If a sterile connection device is used to prepare the aliquot, the expiration date is dependent on the storage container used for the aliquot. Cellular components stored in syringes have an expiration of 4 hours, but if stored in an FDA-approved transfer bag, the expiration remains the same as that of the “mother” unit. Aliquoting volumes multiple times from the primary container may be appropriate to minimize waste and to reduce donor exposure. The facility should have policies, processes, and procedures on the minimum threshold volume of the primary container after which the component may not be transfused as a “whole” unit. Rejuvenation
Volume Reduction of Platelets Decreasing the supernatant substances of platelets (whole-blood-derived or apheresis platelets) may be clinically required to reduce the total transfusion volume to prevent transfusion-associated circulatory overload (TACO) or to partially remove incompatible ABO alloantibodies. Volume reduction performed in an open procedure reduces the expiration date of the platelet to 4 hours. Volume reduction may also be performed using a closed system (sterile connection device). If a sterile connection device is used, the transfusion should be completed as soon as possible, because of the minimal amount of plasma remaining in the component. Volume-reduced platelets are stored at 20-24 C.
The use of an FDA-licensed solution of pyruvate-inosine-phosphate-adenine (PIPA) has been shown to restore the decreased levels of 2,3-DPG and adenosine triphosphate to normal in stored red cells. This solution has been licensed for use with citrate-phosphate-dextrose (CPD) and citrate-phosphate-dextroseadenine-1 (CPDA-1) RBC units within 3 days after the expiration date of the original component19 or at the 42-day expiration of CPD/AS-1.20 Studies have shown that the addition of PIPA to CPD/AS-3 and CPD/AS-5 (although not licensed for this use) provides similar results.16, 21 The rejuvenated RBCs may be glycerolized and frozen for additional storage time (see Method 6-6). The thawed rejuvenated component must be deglycerolized
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One Aliquot (one syringe) Spike Filter – Transfer Bag – 1 Syringe Set Filter
60 cc syringe
= Clamp
= Heat seal
150 mL transfer bag
Sterile dock here
“Mother bag”
Two Aliquots (two syringes) Drawn at the Same Time Filter – Transfer Bag – 2 Syringe Set
Spike
60 cc syringe 60 cc syringe
Filter
= Clamp
= Heat seal
150 mL transfer bag
“Mother bag” Sterile dock here
FIGURE 9-1. Schematic diagrams of syringe aliquoting devices. Single-syringe and double-syringe sets are depicted showing points of sterile welding to original container, points of clamping tubing for transferring component to transfer bag and then to the syringe (or syringes), and final heat sealing points before detaching from original component bag.
before immediate transfusion or stored for up to 24 hours at 1 to 6 C. IN S P E C T I O N , S H I P P IN G , RE CE IV IN G IN TO INVE N TO R Y, DI S P OS IT I O N, A N D IS SUE Inspection A major critical control point in blood component manufacturing, on receipt from another facility, or before issue for transfusion is inspection of the component before disposition.3(pp17,40-41,50) Proper electronic or manual
documentation of this process includes the following: 1) date of inspection, 2) donor identifying number, 3) description of any visual abnormalities, 4) action taken, and 5) identity of the staff performing the inspection. Any questionable component inspection requires the component to be quarantined until final disposition is determined. Visible abnormalities may include segments appearing lighter or darker in color than the primary bag contents, purple color to the red cells, clots, white particulate matter in the primary container, supernatant fluid
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that is discolored from normal appearance, gross lipemia, and foreign objects in the primary container or ports. Green-colored plasma resulting from increased bilirubin pigments (biliverdin) or birth-control pills is not considered a reason for quarantine but must be distinguished from a green color caused by bacterial contamination (eg, Pseudomonas species) or a green-brown color associated with liver or pancreatic disease. A conservative approach would be to quarantine or return to the blood supplier those components that have questionable color. Current requirements for screening platelet components for bacteria should reduce the possibility of moderate or severe bacterial contamination. Other components that appear suspect should be quarantined and cultured. Positive cultures may be related to the donor’s arm (eg, scarring, skin disease such as psoriasis), donor arm preparation, contamination during microbiology processing, handling or pooling of the component, or infection in the donor. If it is determined that a bacterially contaminated component exists, then the component manufacturer should be notified so an immediate investigation can take place. Other components prepared from that collection should be quarantined until the investigation is completed. If the component has been transfused, then the recipient’s attending physician should be informed and consultation with the medical director is recommended.
Shipping Validation of all shipping or transport containers is required before they are placed into use. The containers must be able to maintain the proper transport temperature that is appropriate for the component. Shipping transit time, mode of transport, climatic conditions to which the container may have been exposed, presence of residual wet or dry ice
upon receipt, appearance of the component (or components), and expiration date of the component (or components) should be evaluated. Any deviation from routine shipping or component conditions should be reported to the shipping facility and documented according to each location’s policies, processes, and procedures. Similar evaluation of blood components transported between blood centers, between hospitals, and between blood centers and hospitals should be performed by the receiving facility. Whole Blood, RBCs, and FFP (After Thawing) Whole Blood, RBCs, and FFP (after thawing) must be transported at a temperature of 1 to 10 C. Bagged wet ice, commercial cooling packs, or specially designed containers may be used to maintain acceptable transport temperatures. In order to avoid hemolysis, the Whole Blood, RBCs, and segments should never come into direct contact with the bagged ice or cooling pack. Blood components transported at 1 to 10 C or stored at 1 to 6 C may need to be removed from those temperatures for manipulation (eg, entering into inventory, irradiating). The maximum number of units that can be manipulated in a 30-minute time frame should be determined and not exceeded. Platelets, Thawed CRYO, and Granulocytes Platelets, thawed CRYO, and granulocytes must be transported at a temperature of 20 to 24 C. Well-insulated containers with appropriate coolant are recommended. If the transit time will be >24 hours for platelet shipment or if extreme climate conditions are anticipated, then double-insulated containers or roomtemperature coolant bags should be used. Frozen Components Frozen components should be packaged to minimize breakage and to maintain the components in a frozen state. Dry ice in a suitable
Copyright © 2008 by the AABB. All rights reserved.
CHAPTER 9
Blood Component Storage and Distribution
container is routinely used for shipping these components. The amount of dry ice is dependent on the container, the distance for transport, and the ambient temperature that will be encountered. The dry ice may be layered by starting on the bottom of the container and then spreading a layer of dry ice over each component layer, ending with dry ice on the top of the final component layer.
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red cell components and Rh typing of RBC units labeled as Rh negative (confirmatory testing for weak D is not required).3(p43) Granulocytes must also be ABO retyped, and Rh retyped if labeled as Rh negative (confirmatory testing for weak D is not required) because this component contains 20 to 50 mL of red cells. Transfusion Service Issuing of Components
Receiving into Inventory and Disposition The receiving facility should notify the shipping facility of any deviation from normal appearance of the shipped blood components or absence of wet or dry ice. Documentation of the abnormal condition should be performed according to each facility’s policies, processes, and procedures. Any blood component not meeting the facility’s policies, processes, and procedures should be physically and electronically quarantined. Only after investigation of the deviation and determination that the component meets acceptable criteria may the component be removed from quarantine and released into the general blood inventory. Tracking the disposition of blood and blood components is required from collection to either transfusion or discard. Electronic or manual records are generated indicating compliance with policies, processes, and procedures. Any deviation is recorded, and blood components not meeting requirements should be quarantined or discarded as biohazardous material. Deviations are investigated to determine possible corrective actions, and results of the corrective action are reported to the blood supplier, as needed. Inventory management should consist of routine determination that all blood components have been disposed of properly and that there are no “lost products.” Additionally, policies, processes, and procedures for hospital transfusion services must include ABO retyping before transfusion of
Ensuring that the correct blood component is being issued to the correct patient is paramount in preventing a transfusion mishap. Systems should be in place, either electronic or manual processes, to check the component’s unique blood number, recipient’s name and another patient identifier, blood type, expiration date, crossmatch status or other serologic information (eg, cytomegalovirus negative), documentation of status of visual inspection, time and date of issue, and person (or location if sending by pneumatic tube) to whom (or where) it is issued. When the component is issued to an individual, that individual should conduct a second check on the correctness of the component information (label, computer or manual log information) and manually provide a signature or use an electronic badge or personnel identification number. If all checks are correct, the unit may be issued. Issue of a component to more than one patient at any one time is not recommended; issue of multiple components for multiple patients at any one time is also not recommended. If more components for immediate transfusion are required, then use of a validated cooler is an acceptable alternative to help prevent component-recipient mix-ups before transfusion. Return of Blood Components and Reissue The transfusion service may receive back into the blood component inventory those units that meet acceptance specifications. These
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conditions include the following: 1) the primary container has not been entered, 2) the appropriate transport or storage temperature of the component has been maintained or the component has been returned within a prescribed time frame from issue, 3) at least one sealed segment remains integrally attached to the container of RBCs, and 4) visual inspection of the component is satisfactory. If individual unit temperature indicators are not being used or if the blood components are not being transported in validated transport containers, Whole Blood, RBCs, and FFP (after thawing) may be returned to the transfusion service’s inventory provided that the appropriate temperature has been maintained. Although not stipulated by current accrediting organizations or regulatory agencies, studies have indicated that these previously refrigerated components will maintain a temperature <10 C if not held at ambient room temperature for longer than 30 minutes.22 Therefore, many transfusion services use this time as acceptable for return and pos-
sible reissue of Whole Blood, RBCs, and FFP (after thawing). Platelets returned to the transfusion services greater than 30 minutes from issue may be placed back into inventory following a visual inspection of the component. The presence of swirling platelets in the platelet bag correlates with pH values, and is one criterion for adequate platelet in-vivo viability.23 The platelet bag can be held in front of a light source and gently squeezed to check the “swirling” appearance of the platelets. If “swirling” is evident and there is no visible clumping of the platelets, they may be returned into inventory. The platelet component should be agitated for at least 10 minutes before reissue. Documentation of all acceptable or unacceptable conditions must be carried out. Depending on the criterion not met, the component may either be placed in quarantine for further investigation or discarded in a biohazard container. If the component is accepted, it may be returned to the general blood inventory and reissued.
RE FE RE N CES 1. Food and Drug Administration. Drugs; current good manufacturing practice in manufacture, processing, packing, or holding. Docket No. 636336. (June 19, 1963) Fed Regist 1963;133:6385-7. 2. Code of federal regulations. Title 21 CFR Parts 210 and 211. Washington, DC: US Government Printing Office, 2007 (revised annually). 3. Price TH, ed. Standards for blood banks and transfusion services. 25th ed. Bethesda, MD: AABB, 2008. 4. Clarification offered for storage versus transport of blood components in monitored coolers. AABB Weekly Report 2006;12:4-5. 5. Beutler E. Red cell metabolism and storage. In: Anderson KC, Ness PM, eds. Scientific basis of transfusion medicine. Philadelphia: WB Saunders, 1994:188-202. 6. Heaton A, Keegan T, Holme S. In vivo regeneration of red cell 2,3-diphosphoglycerate follow-
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ing transfusion of DPG-depleted AS-1, AS-3, and CPDA-1 red cells. Br J Haematol 1989;71:131-6. Strauss GS. Additive solutions and product age in neonatal blood transfusions. In: Hermann JH, Manno CS, eds. Pediatric transfusion therapy. Bethesda, MD: AABB Press, 2002:131-9. Vassallo R. Preparation, preservation, and storage of platelet concentrates. In: Simon TL, Snyder EL, Stowell CP, et al, eds. Rossi’s principles of transfusion medicine. 4th ed. Bethesda, MD: AABB Press, 2008 (in press). Brumit MC, Hay SN, Brecher ME. Bacteria detection. In: Brecher ME, ed. Bacterial and parasitic contamination of blood components. Bethesda, MD: AABB Press, 2003:57-82. Beaudoin J. Baxter collaborates with Gambro BCT on 7-day platelet study to speed adaption (May 17, 2006). Deerfield, IL: Baxter Healthcare, 2006. [Available at http://www.baxter.com/
Copyright © 2008 by the AABB. All rights reserved.
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Blood Component Storage and Distribution
about_baxter/news_room/news_releases/2006/ 05-17-06-platelet_study/html (accessed November 4, 2007).] Downes KA, Wilson E, Yomtovian R, Sarode R. Serial measurement of clotting factors in thawed plasma stored for 5 days (letter). Transfusion 2001;41:570. AABB, American Red Cross, and America’s Blood Centers. Circular of information for the use of human blood and blood components. Bethesda, MD: AABB, 2002. Calhoun L. Blood product preparation and administration. In: Petz LD, Swisher SN, Kleinman S, et al, eds. Clinical practice of transfusion medicine. 3rd ed. New York: Churchill Livingstone, 1996:305-33. Leukocyte reduction. Association bulletin #9907. Bethesda, MD: AABB, 1999. Meryman HT, Hornblower M. A method for freezing and washing RBCs using a high glycerol concentration. Transfusion 1972;12:145-56. Lockwood WB, Hudgens RW, Symanski IO, et al. Effects of rejuvenation and frozen storage on 42-day-old AS-3 RBCs. Transfusion 2003;43: 1527-32. Valeri CR. Glycerolization and deglycerolization of red blood cells in a closed system using the Haemonetics ACP215. Boston, MA: Naval Blood
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Research Laboratory, 2006. [Available at http:// www.nbrl.org/projects.html#rbc (accessed November 4, 2007).] Anglini A, Dragani A, Berardi A, et al. Evaluation of four different methods for platelet freezing: In vitro and in vivo studies. Vox Sang 1992; 62:146-51. Valeri CR, Zaroules. Rejuvenation and freezing of outdated stored human red cells. N Engl J Med 1972;287:1307-13. Szymanski IO, Teno RA, Lockwood W, et al. Effect of rejuvenation and frozen storage on 42day AS-1 red cells. Transfusion 2001;41:550-5. Valeri CR, Pivacek LE, Cassidy GP, Ragno G. The survival, function, and hemolysis of human RBCs stored at 4 C in additive solution (AS-1, AS-3, or AS-5) for 42 days and then biochemically modified, frozen, thawed, washed, and stored at 4 C in sodium chloride and glucose solution for 24 hours. Transfusion 2000;40:1341-5. Pick P, Fabijanic J. Temperature changes in donor blood under different storage conditions. Transfusion 1971;11:213-15. Bertoloni F, Murphy S. A multicenter inspection of the swirling phenomenon in platelet concentrates prepared in routine practice. Transfusion 1996;36:128-32.
Copyright © 2008 by the AABB. All rights reserved.