Washed and Volume-Reduced Blood Components

Chapter 29

Washed and Volume-Reduced Blood Components S. Gerald Sandler ● Viviana V. Johnson Jayashree Ramasethu

INTRODUCTION

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Standard red blood cell (RBC) or platelet components may be washed or volume-reduced to make them more suitable for patients who have special transfusion requirements. In the United States, blood components for transfusion are standardized to comply with applicable federal statutes and regulations of the Food and Drug Administration (FDA).1 Typically, community blood centers collect blood from donors and supply hospital transfusion services with standard FDA-licensed blood components. Some hospital transfusion services modify RBC or platelet components by washing with 0.9% sodium chloride (“normal saline”) or by centrifugation to reduce the volume of plasma or anticoagulant-preservative solution. While the rationale for transfusing these modified blood components in selected recipients may be medically sound, the methods for their preparation are often not standardized and their therapeutic efficacy is not well established. Washed or volume-reduced blood components may be considered to be the latest step in the process of improving the match between the blood products that are collected from donors and the products that are needed by individual patients. In 1937, two decades after the introduction of blood transfusions of stored whole blood,2 concentrated RBCs were introduced as an alternative to whole blood for anemic patients who were at risk for hypervolemia.2,3 Early experience transfusing concentrated RBC components established lower rates of adverse transfusion reactions compared with conventional whole blood.4 The subsequent development of sterile plastic collection bags and refrigerated centrifuges facilitated the separation of whole blood collections into RBC, plasma, and platelet components. This advance made it possible to match standardized blood components to categories of patients, but these generic blood components did not always meet the requirements of individual patients. The introduction of washed or volume-reduced blood components allowed physicians to further customize blood transfusions for the requirements of specific patients. The following chapter summarizes current indications and methods for preparing washed or volume-reduced RBC and platelet components. The methods for preparing the modified blood components may vary in technical detail, depending on the specific RBC or platelet component selected for washing or volume reduction. In this chapter, the generic term RBC component applies to all RBC-containing components that are categorized as Red Blood Cells in the

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●

FDA-approved Circular of Information.1 The term platelet component applies to either Platelets (random donor platelet concentrates) or Platelets Pheresis (apheresis platelets), as described in the Circular of Information.1

WASHED RED BLOOD CELLS Transfusion services may wash standard RBC components using automated cell washing systems to prepare Washed Red Blood Cells for selected patients. This procedure decreases their risk of adverse effects from constituents of plasma (i.e., plasma proteins, antibodies, electrolytes), from constituents of anticoagulant-preservative-storage solutions (i.e., citrate, adenine, dextrose, mannitol), and from glycerol, which is occasionally used to freeze RBC units (Table 29–1). Washing RBC components removes approximately 90% of leukocytes, 20% to 90% of platelets, and nearly all plasma proteins, including unwanted donor antibodies.5 In many situations, RBC components are washed to decrease the potassium concentration or remove potentially allergenic plasma proteins. During intraoperative salvage of shed blood, recovered RBCs are washed to remove clots, leukocytes, platelets, cellular debris, and heparin. Previously, RBC components were routinely washed before transfusion in patients with paroxysmal nocturnal hemoglobinuria (PNH), but recent studies demonstrate that this precaution is unnecessary (see below).

Indications for Washed Red Blood Cells Large-Volume or Rapid Transfusion to Newborns and Other Small Children Small-volume transfusions (<25 mL/kg) of CPDA-1“packed” RBC components or RBC components in extended-storage media (AS-1 [ADSOL]; Baxter Healthcare Corporation, Deerfield, Ill.; AS-3 [Nutricel]; Medsep Corporation, Covina, Calif.; AS-5 [Optisol]; Terumo Corporation, Somerset, N.J.) may be safely transfused to small children, including newborns and preterm infants.6 However, large-volume transfusions (>25 mL/kg) of conventionally stored RBC components, particularly if transfused rapidly, may cause acute hyperkalemia, cardiac arrest, and death.7 During refrigerated storage of RBC components, potassium leaks from the intracellular fluid of RBCs, increasing potassium concentration in the plasma (or in the anticoagulant-preservative solution) to levels that are potentially dangerous for rapid transfusions in susceptible recipients.

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Clinical Indications and Rationale for Washed RBC Components

Clinical Indication

Rationale

Large-volume or rapid transfusion

Particularly in newborns and small children, decreases risk of hyperkalemia and cardiac arrhythmias Decreases potassium in plasma or additive solution Removes allergenic plasma proteins, whether or not they are specifically identified Removes clots, cellular debris, and heparin and suspends shed RBCs in saline solution During ongoing hemolysis, reduces further hemolysis by eliminating IgM anti-T present in normal donors’ plasma No longer recommended

Following gamma irradiation and storage Allergic or anaphylactic reaction Intraoperative salvaged autologous blood T-activation Paroxysmal nocturnal hemoglobinuria

The potassium concentration in plasma of CPDA-1 RBC components increases from 4.2 mmol/L to nearly 80 mmol/L during the 35-day storage period.6 For a 1-kg newborn, a conventional transfusion (15 mL/kg) of 42-day stored AS-1 RBCs (hematocrit of 80%) may have a potassium concentration as high as 50 mEq/ L, but the total potassium content is only 0.15 mEq. While that relatively high concentration of potassium is tolerable and safe if the component is transfused slowly (over 2 to 4 hours), the same component could present a potentially fatal acute potassium load if transfused rapidly in a small child or susceptible adult. Rapid transfusions of stored RBC components in such patients may increase potassium acutely and, therefore, require washed or freshly collected RBC components. Typical situations include exchange transfusions, extracorporeal membrane oxygenation (ECMO), cardiopulmonary bypass, or solid organ transplantation.8–10 Washed RBC components should also be considered for large-volume (>25 mL/kg) or rapid transfusions in newborns and other small children with renal failure, hyperkalemia, or severe acidosis. Some physicians are also concerned that the doses of certain additives in extended-storage solutions (AS-1, AS-3, AS-5) may exceed known limits for safety for large-volume transfusions in small children.11 These concerns derive from the theoretical possibility that constituents in the storage media could contribute to hyperosmolality, hyperglycemia, hypernatremia, or hyperphosphatemia. For that reason, some transfusion services routinely wash or volume-reduce RBC components stored in additive solutions for large-volume or rapid transfusions in newborns or other small children. Transfusion of RBC Components following Gamma Irradiation To prevent transfusion-associated graft-versus-host disease (TA-GVHD) in immunocompromised or other patients who are at risk, transfusion services (or blood centers) routinely gamma-irradiate blood components with a dose of 2000 to 3000 cGy. Although gamma-irradiation is highly effective for preventing TA-GVHD, irradiation has adverse effects on RBC survival, plasma hemoglobin concentration, and RBC ATP.12–15 Plasma potassium concentration nearly doubles during the 48 hours after RBC components are irradiated with 3000 cGy.12 Gamma-irradiation increases passive permeability of RBC membrane lipid bilayers, resulting in a progressive, reciprocal increase in intracellular sodium and decrease in intracellular potassium.13 AABB Standards requires RBC components to outdate no longer than 28 days from the date of irradiation.16 While washing irradiated RBC components reduces potassium concentration

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in the supernatant, it does not arrest the process. From the time irradiated RBC components are stored following washing, potassium concentration increases in a time-dependent fashion, which is more rapid than for nonirradiated RBC components. The potassium concentration in irradiated and washed RBC components may reach a critical concentration of 5 mEq/L after only 3 hours of storage at 4°C, compared with 6 hours for nonirradiated washed RBC components.17

WASHED AND VOLUME-REDUCED BLOOD COMPONENTS

Table 29–1

Allergic or Anaphylactic Reactions Mild, first-time allergic transfusion reactions (hives, flushing, pruritus) often seem to be product-related, rather than patient-related. These reactions typically respond to antihistamines and do not recur when additional plasma-containing blood components are transfused. In contrast, some chronically transfused persons develop more serious and generalized allergic reactions (bronchospasm, rash, nausea, vomiting, or diarrhea) that are not prevented by, or respond to, treatment with antihistamines. Transfusing washed RBC components usually prevents allergic reactions in such patients. If acute allergic reactions progress to life-threatening anaphylaxis, bronchospasm, and hypotension, a diagnosis of an immunoglobulin A (IGA) anaphylactic reaction should be considered.18 Conventionally, that diagnosis is made by demonstrating IGA deficiency (by a highly sensitive passive hemagglutination inhibition assay) and the presence of anti-IgA (by passive hemagglutination assay).19 However, we advise caution when interpreting results of IgA hemagglutination assays because they may yield nonspecific results.20 The same hemagglutination assay that is used to diagnose patients with IgA anaphylactic reactions detected IgA deficiency and the presence of anti-IgA in 1:1200 asymptomatic healthy blood donors.19 Clearly, this number of healthy persons at risk for an IgA anaphylactic reaction greatly exceeds the incidence of IgA anaphylactic transfusion reactions in clinical practice. Nonetheless, if the diagnosis of IgA deficiency is made, RBCs and platelets can be washed with high volumes of saline (4–6 L) to effectively remove plasma antibodies. Washed RBC and platelet components have been transfused successfully in persons with IgA deficiency and anti-IgA who had a history of anaphylactic transfusion reactions when blood components from IgA-deficient donors were not available.21,22 Other severe generalized reactions to plasma-containing blood components that may be abrogated by washing components prior to transfusion include transfusion-related acute lung injury (TRALI), leukocyte-mediated cytokine reactions, and anaphylaxis in persons with ahaptoglobinemia and antihaptoglobin.23

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Intraoperative Salvage of Shed RBCs Intraoperative salvage of shed RBCs has been used for more than four decades to reduce the number of allogeneic blood transfusions in trauma and surgery associated with largevolume blood loss.24–26 Typically, shed blood is aspirated from the sterile surgical field, anticoagulated using a heparin-saline solution, and washed with 0.9% sodium chloride in an automated cell salvage machine. The effluent containing clots, leukocytes, platelets, cellular debris, and heparin is discarded. Saline-washed concentrated autologous RBCs are returned to the patient. When suitable wash volumes are used, activated coagulation factors, cytokines, and heparin are substantially reduced.27–32 An alternative method of salvaging shed autologous RBCs involves collecting heparinized sanguineous drainage from the chest, large joints, or other sites that is returned directly (unwashed) from collection canisters.33–36 Postoperative infusion of unwashed filtered blood has been reported to be effective and without clinically relevant complications in orthopedic patients.33,34 However, this method is controversial, because such drainage may contain procoagulant material, variable amounts of anticoagulant, and unsterile debris.35 Even saline-washed salvaged RBCs collected under optimal conditions may contain residual biologically active materials capable of causing increased vascular permeability, acute respiratory distress syndrome, or disseminated intravascular coagulation.36,37 These complications, which have been described as the “salvaged blood syndrome,” can be averted by standardizing aspiration methods, controlling saline wash volumes, and monitoring for an abnormal accumulation of debris on the inner wall of the rotating bowl.36 T-Activation of RBCs Immune-mediated hemolysis has been reported following transfusion of plasma-containing blood components to patients whose RBC T-crypt antigens have been exposed by bacterial infection.38–40 T-activation occurs when bacterial neuraminidase removes N-acetyl neuraminic acid and exposes RBC T-crypt antigens. Exposed T-crypt antigens bind with IgM anti-T, a normal constituent of adult plasma, resulting in RBC agglutination (polyagglutination) and hemolysis. T-activation has been reported to occur in a wide range of bacterial infections, including necrotizing enterocolitis, septicemia, hemolytic uremic syndrome, and Streptococcus pneumoniae infection. T-activation should be suspected in children who have the onset of intravascular hemolysis following transfusion of plasma-containing blood components. T-activation has been diagnosed less frequently in recent years because many hospital transfusion services now use non-plasma-containing monoclonal typing reagents instead of traditional plasma-derived blood typing reagents (anti-A, -B, and -A,B). Previously, some cases of clinically unrecognized polyagglutination due to T-activation were detected during routine compatibility testing using plasma-derived ABO typing reagents. Discrepancies in forward and reverse ABO typing results caused by polyagglutination or in vitro hemolysis suggested T-activation. T-activation is confirmed by specific agglutination tests using Arachis hypogaea and Glycine soja lectins. To prevent further hemolysis in patients who have active hemolysis and polyhemagglutination, RBC (or platelet) components should be washed using 0.9% sodium chloride before transfusion. Exchange transfusion

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with plasma-reduced components may be necessary for infants with T-activation and ongoing hemolysis.39 In patients with T-activation, some physicians recommend completely avoiding transfusions of fresh frozen plasma, platelets, or other plasma-containing blood products. Others question the clinical importance of T-activation and recommend that if plasma-containing components are indicated, they should not be withheld.41 Recommendations, which are based on case reports, are conflicting and there are neither evidenced-based guidelines nor results of a randomized, controlled clinical trial to direct practice. The authors concur with the preponderance of clinical evidence, which favors not withholding plasma-containing blood components when they are indicated. The authors do not recommend that transfusion services, which routinely use murine or other monoclonal blood typing reagents, consider adding human plasma–derived typing reagents as a screening procedure to detect T-activation. Paroxysmal Nocturnal Hemoglobinuria PNH is an uncommon stem cell disorder manifested by complement-mediated hemolytic anemia, thrombophilia, and marrow failure.42–44 The mainstay of managing the typical Coombs-negative, treatment-resistant, intravascular hemolytic anemia is RBC transfusions.45 Promising results have been reported for managing hemolysis using eculizumab, a humanized monoclonal antibody to complement C5.46 However, the role for this new treatment has yet to be defined. In 1948, Dacie reported that blood transfusions exacerbated complement-mediated intravascular hemolysis in patients with PNH, increasing hemoglobinuria and hemoglobinemia.47 As a consequence, some hematologists request washed RBC components for routine transfusions in patients with PNH. Admittedly, post-transfusion hemolysis is rare in patients with PNH when washed RBC components are transfused,47 although it has been reported.48,49 However, it should be noted that most PNH patients do not experience hemolysis after RBC transfusions, even when whole blood is transfused.50 A retrospective review of 23 PNH patients who were transfused with a total of 556 units of whole blood, packed RBCs, leukocyte-poor RBCs, washed RBCs, frozen RBCs, and intraoperatively salvaged RBCs, identified only one case of post-transfusion hemolysis.51 This case occurred after transfusion of group O whole blood to a group AB-positive recipient. This specific serologic incompatibility is similar to that in the 1948 case reported by Dacie, which is the origin of the practice of washing RBC components before transfusion to patients with PNH.47 Based on this large-scale study, a supporting opinion from the PNH Interest Group,52 as well as the authors’ own uneventful personal experiences transfusing patients with PNH with unwashed AS-1 RBCs, we believe that transfusing washed RBC components to PNH patients is unwarranted.

Methods for Preparing Washed Red Blood Cells RBC components may be washed manually using a refrigerated centrifuge or, more commonly, an automated cell washer. Washing an RBC component using 1 to 2 L of 0.9% sodium chloride removes approximately 99% of plasma proteins, electrolytes, and antibodies but may result in loss of up to 20% of the RBCs depending on the protocol.53 Rarely,

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Alternatives to Washed Red Blood Cells For certain clinical situations, there may be alternatives to washed RBC components for reducing the potassium concentration or removing plasma proteins. For rapid transfusions in small infants, reconstituted whole blood (i.e., RBCs resuspended in fresh-frozen plasma shortly before transfusion), should dilute supernatant potassium to a safe concentration. According to the AABB Pediatric Hemotherapy Committee, “reconstituted whole blood . . . or whole blood (<5 days old) may be given [to infants and children <18 years] without the need for further justification in the setting of massive transfusions.”54 Additionally, selecting an RBC component stored in AS1, AS-3, or AS-5 preservative-storage solutions, rather than as packed CPDA-1–anticoagulated RBCs in plasma, should reduce the concentration of plasma proteins to a level tolerable for most patients with mild, recurrent allergic reactions.

VOLUME-REDUCED RED BLOOD CELL COMPONENTS Hospital transfusion services may prepare volume-reduced RBC components for newborns or other small children who require transfusions but whose capacity to receive additional intravenous fluids is limited. Volume-reduction methods are intended primarily for AS-1 and AS-3 RBC components (hematocrit 60%) because “packed” CPDA-1 RBC components (hematocrit 75% to 80%) are already concentrated.

Indications for Volume-Reduced RBC Components Volume-reduced RBC components are indicated when the intended recipient has a need for RBC transfusion (e.g., symptomatic anemia), but the patient’s circulatory system cannot tolerate the additional volume. In adults, this situation may be the consequence of renal or cardiac insufficiency. In newborns, it may result from competition between intravenous nutrition protocols, medications, and blood components for the relatively small volume that the infant’s circulation can tolerate. Transfusion of volumereduced RBC components in volume-sensitive infants and small children is controversial. Not all physicians agree that recentrifugation of conventional RBC components with additive solutions (hematocrit 60%) to prepare volume-reduced RBCs (hematocrit 85% to 87%) is a clinically meaningful procedure. Alternatives to volume-reduction of RBC components include transfusing less volume or selecting (“packed”) CPDA-1 RBC components, which have a higher hematocrit.

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Methods for Preparing Volume-Reduced Red Blood Cells AS-3 Red Blood Cells Conventional Red Blood Cells are prepared by removing supernatant plasma from Whole Blood following a “heavy spin” (5000 × g, 5 minutes).55 Removing 225–250 mL of plasma results in an RBC component with a hematocrit of 70% to 80%. The hematocrit of the final component may be decreased by removing proportionally less plasma.55 Strauss and colleagues developed a method to prepare multiple aliquots of RBCs for neonatal transfusions with hematocrit >90% using RBC components stored at 4°C for as long as 42 days.56 For this method, donor blood is collected in a primary bag containing CP2D anticoagulant (Leukotrap RC System, Miles Inc., Elkhart, Ind.), which is centrifuged at 5000 × g for 5 minutes. Platelet-rich plasma is transferred to a second bag, which is disconnected. Extended storage media (100 mL) (Nutricel, AS-3, Miles) is added to the storage bag, and after mixing, the RBCs are transferred via the leukocyte-reduction filter to another storage bag. A cluster of small-volume bags is attached to the storage bag using a sterile connecting device. When a transfusion is ordered, the storage bag is centrifuged in an inverted position to pack the AS-3 RBC component to a hematocrit of approximately 90%. Strauss modified the original method to centrifuge at 4000 × g for 4 minutes, not faster as in the original description.57 The volume of RBCs requested flows from the bottom of the storage bag through the outlet tubing into one of the small-volume bags. The aliquot is disconnected, and the residual contents of the storage bag are mixed thoroughly and returned to storage until the next aliquot is required. During storage, AS-3 RBCs are mixed and resuspended weekly. In the original study, measurements of extracellular potassium, hemoglobin, and lactic dehydrogenase from repeatedly mixed and centrifuged units that were stored in inverted position were comparable to those of uncentrifuged, conventionally stored AS-3 RBCs.56

WASHED AND VOLUME-REDUCED BLOOD COMPONENTS

recipients who have acute reactions to even small quantities of residual plasma require RBC components that have been washed using 4 to 6 L of saline. If the objective of washing is to remove leukocytes, platelets, and plasma, the cell washer may be programmed to remove the buffy coat, which will increase loss of RBCs. If RBC components are already leukocyte-reduced prior to washing, there is no requirement to remove the buffy coat and RBC loss will be minimized. Most transfusion services use cell washers with an “open” system, which limits the duration of refrigerated storage (1°C–6°C) to 24 hours.

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AS-1 Red Blood Cells The method described above for AS-3 RBC components has been modified to prepare AS-1 RBC components with hematocrits of approximately 85% to 87% after storage at 4°C for as long as 42 days.58 For this method, AS-1 RBC components (Adsol, Baxter Healthcare Corp., Deerfield, Ill.) are processed and stored by conventional methods with hematocrits of approximately 60%. When a transfusion is requested, the AS-1 RBC component is centrifuged in an inverted position at 4000 × g for 4 minutes. Aliquots are removed, as above. During storage, the primary AS-1 RBC component is remixed and stored until another transfusion is ordered and aliquots are removed. We concur with the authors of this method, who caution that “. . . this technique may not be desired by all centers, and if it is adopted, quality control studies should be performed to ensure the quality and sterility of the RBC aliquots.”58 Inverted Gravity Sedimentation Storing RBC components in the refrigerator “upside down” (inverted gravity sedimentation) will concentrate AS-1 RBC components to a hematocrit of approximately 68% by 72 hours.59 This simple manipulation provides a method for volume-reducing AS-1 RBC components in transfusion services that may not have access to an appropriate refrigerated centrifuge.

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WASHED PLATELET COMPONENTS Washed platelet components contain less plasma, but the procedure also decreases the total platelet content and may decrease platelet function. Therefore, washing platelet components is not recommended, except for relatively limited clinical indications60 (Table 29–2).

Indications for Washed Platelet Components Recurrent Allergic or Anaphylactic Transfusion Reactions Patients who require washed RBC components because of recurrent allergic or anaphylactic transfusion reactions may also require washed platelet components (see above). Neonatal Alloimmune Thrombocytopenia

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Neonatal alloimmune thrombocytopenia (NAIT) is a potentially fatal disease of the fetus or newborn that may occur when there is serologic incompatibility for human platelet antigens (HPAs) between mother and fetus. More than 16 different HPAs have been implicated in NAIT.61 Approximately 90% of cases of NAIT in Caucasians of European ancestry present in an HPA-1a–positive newborn or fetus of an HPA-1a–negative mother who has developed anti-HPA-1a.62 Approximately 6% to 19% of cases of NAIT in Caucasians are due to anti-HPA-5b and 0% to 2% are due to anti-HPA-1b.63,64 Mothers of Asian ancestry whose newborns have NAIT most often have antibodies specific for HPA-4 antigens.65 One approach to managing an at-risk pregnancy consists of using periumbilical blood sampling (PUBS) to monitor fetal platelet counts after 20 weeks of gestation and infusing the mother with intravenous immune globulin (IVIG) (1 g/ kg) weekly to decrease the risk of fetal thrombocytopenia.66 In this protocol, adding dexamethasone (1.5 mg) to weekly infusions of IVIG did not improve the response rate. In an alternative approach, the fetus’s platelet count is measured at 20 weeks of gestation and the mother receives weekly infusions of IVIG (1 mg/kg) if the fetus is thrombocytopenic.67 A second PUBS is performed at 26 weeks, and if the fetus remains thrombocytopenic, prednisone (60 mg daily) is added to weekly IVIG infusions. PUBS is repeated before delivery and, if thrombocytopenic, the fetus is transfused with platelets.67

Since maternal platelets are serologically compatible with the offending antibody in NAIT, the mother is a potential source of platelets for transfusion in the newborn.68 However, maternal platelets are collected in the mother’s plasma, which contains the offending antibody. Therefore, it is necessary to wash the maternal platelet component and resuspend the maternal platelets in compatible plasma, 0.9% sodium chloride, or a platelet storage solution. Platelet components may be washed by manual or automated methods using 0.9% sodium chloride, with or without adding ACDA.69 Such washing may result in loss of as many as 33% of the original platelets.70 Since washing presently requires an “open” system, and since platelets must be stored at 20°C to 24°C, washed platelet components must be transfused within 4 hours. A limited number of blood centers are able to supply HPAmatched platelet components collected from HPA-typed and qualified donors.70 Usually, the donor panels are limited to HPA-1a–negative platelet donors, since this is the most frequently required HPA phenotype. In some blood centers, these platelet donors are scheduled for platelet apheresis collections at frequent intervals, so that their platelet components qualify for “emergency release” protocols (provided that recent test results are acceptable). In the authors’ experience, serologically compatible platelet components collected from such call-in donors may be collected and emergencyreleased faster than collecting, testing, and processing platelet components from the postpartum mother. Donors of less common HPA phenotypes are more difficult to identify and recruit. When maternal platelets or HPA-matched platelets from allogeneic donors are transfused, conventional doses of platelets (10 mL/kg) should be adequate for most clinical situations. Nevertheless, monitoring post-transfusion platelet counts is essential, given the serious consequences of inadequate dosing in thrombocytopenic newborns.

Out-of-Group Platelet Components In many hospitals, platelet components from group O donors are transfused to group A, B, or AB recipients if ABO groupspecific platelet components are not available. Usually, the small volume of donor plasma, representing a “minortype” ABO incompatibility, does not cause overt hemolysis. Recipients of out-of-group platelet transfusions may develop a weakly positive direct antiglobulin test result, but that is typically the only evidence of incompatibility. Occasionally,

Table 29–2 Clinical Indications and Rationale for Washed Platelet Components Clinical Indication

Rationale

Allergic or anaphylactic reactions

Removes allergenic plasma proteins, whether or not they have been specifically identified May be effective in some adults but unproved in children Removes maternal alloantibodies from platelet components collected from the mother, whether or not serologic specificity has been identified Eliminates risk of hemolysis due to anti-A or -B when compatible platelet components are not available for susceptible progenitor cell transplantation or newborn recipients During ongoing hemolysis, reduces further hemolysis by eliminating IgM anti-T present in normal donors’ plasma No longer recommended

Febrile nonhemolytic transfusion reactions Neonatal alloimmune thrombocytopenia Out-of-group platelets T-activation Paroxysmal nocturnal hemoglobinuria

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Methods for Washing Platelet Components Methods have been developed for manual and automated washing using blood cell processors.75–77 Washed platelet components have a threefold increase in spontaneous activation, as well as impaired ADP-induced aggregation, compared with unwashed platelet components.74 Washing platelets requires skill and experience to minimize platelet loss, activation, and clumping.78 Automated cell processors are more likely to deliver a consistent result and are recommended. Kalman and Brown developed a protocol using the IBM 2991 Blood Cell Processor, which removed a mean of 99.6% of plasma proteins following a 1500-mL wash using 0.9% sodium chloride. That cell processor is currently marketed as the COBE 2991 Blood Cell Processor (COBE Laboratories, Lakewood, Colo.). Washed platelet components should be used immediately after washing owing to lack of substrates to support platelet metabolism during storage. In vitro studies of new additive solutions for washing platelets suggest that a postwash storage duration of up to 48 hours may be feasible.79

VOLUME-REDUCED PLATELET COMPONENTS Indications for Volume-Reduced Platelet Components There are two indications for transfusing volume-reduced platelets: to prevent circulatory overload and to lessen the volume of any potentially adverse constituents in the plasma of platelet components. Volume-reduction can be achieved either during collection and processing of collections (primary volume reduction) or subsequently by recentrifu-

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gation of stored platelet components (secondary volume reduction).79 Additional concentration of standard platelet components is controversial. Hypervolemia A typical argument to support the availability of such “super- or hyper-concentrated” platelet components for newborns is that a standard 50-mL unit of random donor platelet components represents more than half the blood volume of a 1-kg infant and may precipitate circulatory overload.80 In vitro studies of recentrifuged, volume-reduced platelet components demonstrated satisfactory viability, and in vivo studies have demonstrated satisfactory survival of 51r-labeled concentrated platelets and post-transfusion platelet count increments.81,82 Arguments against routinely reducing the volume of standard platelet components focus on the reliability of transfusing 5 to 10 mL/kg of standard platelet concentrates or apheresis platelets to increase the platelet count to >100 × 109 L.83 A secondary concern is that while satisfactory concentration of platelets may be achieved by experienced research technologists in a limited study, technologists working in routine transfusion service operations may not be able to achieve that level of quality control. A transfusion service undertaking recentrifugation of platelets must take special precautions to control for platelet loss, clumping, and dysfunction caused by additional handling.78 The AABB Pediatric Hemotherapy Committee published the results of a national survey of neonatal transfusion practices, noting that “because of the potential for harm, institutions transfusing volume-reduced platelets should monitor both the quality of the final product (i.e., the number of platelets, degree of clumping, and function) and in vivo effects such as post-transfusion increment in platelet count and adverse reactions, including altered vital signs and pulmonary distress.”84 The Committee made the observation that 61% of respondents reported a final desired volume of 10 to 15 mL, and an additional 30% desired 18 to 25 mL, both volumes being within the range likely to achieve the targeted platelet count increase using an unmodified platelet concentrate.

WASHED AND VOLUME-REDUCED BLOOD COMPONENTS

acute intravascular hemolysis may occur (e.g., when ABOincompatible apheresis platelet components from donors who have high-titer anti-A/A,B have been transfused to A1 recipients).71,72 As clinical practice shifts from transfusing pools of random donor platelet concentrates (where a high-titer unit is diluted) to transfusing more single-donor (apheresis) platelet components,71 more cases of hemolysis may be identified. Some transfusion services perform anti-A/ anti-A,B titers on group O single-donor platelet components prior to an “out-of-group” transfusion.73 However, there is lack of agreement as to what titer is clinically relevant and whether IgM or IgG antibody is more significant.73 Although washing of out-of-group platelet components removes incompatible plasma, the process may decrease platelet function,74 requires considerable skill and experience,59 and is not practiced routinely. In some hospitals, the practice of washing (or volumereducing) platelet components to prevent anti-A/A,B or anti-B hemolysis is limited to transfusions in progenitor cell transplant (PCT) recipients and newborns. In PCT recipients, transfusion support between myeloablation and engraftment may require washed or volume-reduced platelet components to avoid anti-A/A,B– or anti-B–associated hemolysis. Plasma in platelet concentrates may represent a significant percentage of a newborn’s blood volume, placing newborns at higher risk than adults for ABO-related hemolysis. Some hospitals routinely wash or volume-reduce out-of-group platelet components for newborns.

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Recurrent Febrile Nonhemolytic Transfusion Reactions In adults, the incidence of febrile nonhemolytic transfusion reactions (FNHTRs) is decreased when plasma-reduced platelet components are transfused.85,86 This effect, similar to that of prestorage leukoreduction, is attributed to decreased leukocyte-derived proinflammatory cytokines, which accumulate in plasma of stored platelet components.86,87 In children, a randomized, prospective, crossover study compared the frequency of acute reactions to post storage plasmaremoved platelet components and to standard platelets.88 Study platelet components were prepared by removing plasma from stored components and replacing it with an equal volume of ABO-compatible fresh frozen plasma (FFP). While there was a trend toward lower frequency of FNHTRs with post storage plasma removal, the results were not statistically significant.88 The investigators could not explain why FNHTRs occurred less frequently in children than in adults. On the basis of these findings, the authors do not recommend removing plasma (with or without replacement using FFP) as a method to reduce the incidence of FNHTRs in children. We believe that routine recentrifugation of platelet components is neither necessary nor prudent. As stated by the

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Table 29–3

Methods for Preparation of Secondary Volume-Reduced Platelet Components

Method Moroff et al, 198480 Pisciotto et al, 199195 Ali et al, 199496 Holme et al, 199481 Rock et al, 199897 Zilber et al, 200398 Schoenfeld et al, 200599

Starting Platelet Component Random donor Random donor Random donor Random donor Random donor Random donor Single donor (apheresis)

N

Volume of Final Platelet Component (mL)

Platelet Count of Final Platelet Component (×109/mL)

In Vitro Platelet Function Studied after Volume Reduction

12 6 20 20 12 21 20

15–20 20–25 30–35 30–34; 35–50 10 10, 20 90

Not reported 2.32 Not reported 1.95; 1.39 2.38 Not reported 1.90

Yes Yes No Yes Yes Yes Yes

In Vivo Platelet Efficacy Studied after Volume Reduction No Yes Yes Yes No No No

Modified from Schoenfeld H, Spies C, Jakob C. Volume-reduced platelet concentrates. Current Hematol Rep 2006;5:82–88.

AABB Committee on Pediatric Hemotherapy, “ . . . volume reduction of platelet concentrates . . . should be reserved for special infants for whom marked reduction of all intravenous fluids is truly needed.”84

Methods to Volume-Reduce Platelet Components Primary Volume Reduction

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Primary volume reduction of platelet concentrates occurs at the time of collection and processing of platelet components. Several studies have shown that platelet collections may be concentrated beyond current standards using new, high-efficiency apheresis collection devices with or without specialized platelet storage solutions.89–93 Schoenfeld has evaluated and compared these experimental platelet components.99 Since most hospital transfusion services do not have facilities to collect or adequately monitor the efficacy of such components, this discussion focuses on selective secondary volume reduction of standard platelet components. Secondary Volume Reduction Secondary volume reduction occurs after storage by recentrifugation to remove plasma and resuspend platelets in a decreased volume for immediate transfusion.94 There is no standard method for preparing volume-reduced platelet concentrates. The functional characteristics of secondary volume-reduced platelet components prepared by different methods have been studied (Table 29–3).80–81,95–99 If secondary volume reduction of platelet components is necessary, the authors recommend the method of Moroff and colleagues.80 This method uses standard platelet concentrates that may be stored for as long as 5 days before recentrifugation, a standard blood bank refrigerated centrifuge, and manual resuspension of the centrifuged platelets. Methods for collecting platelets by apheresis and storing them in platelet additive solutions in a reduced volume of plasma have also been developed. Proponents report that decreased plasma reduces allergic and febrile transfusion reactions, facilitates ABO-incompatible platelet transfusions, and is the preferred approach for some pathogen-inactivation methods.100–103

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REFERENCES 1. Circular of Information for the Use of Human Blood and Blood Components. Available at http://www.aabb.org/Documents/About_Blood/ Circulars_of_Information/coi0702.pdf. Accessed March 29, 2006. 2. Robertson LB. Transfusion of whole blood: a suggestion for its more frequent employment in war surgery. Br Med J 1917;2:38–40. 3. Castellanos A. La transfusion de globules. Arch Med Infant 1937; 6:319. 4. MacQuaide DH, Mollison PL. Treatment of anaemia with concentrated red cell suspensions. Br Med J 1940;2:555. 5. Friedberg RC, Chester A. Stem cell transplantation. In Mintz PD (ed). Transfusion Therapy: Clinical Principles and Practice. Bethesda, Md., American Association of Blood Banks, 2005, p 290. 6. Strauss RG. Data-driven blood-banking practices for neonatal RBC transfusions. Transfusion 2000;40:1528–1540. 7. Hall TL, Barnes A, Miller JR, et al. Neonatal mortality following transfusion of red cells with high plasma potassium levels. Transfusion 1993;33:606–609. 8. Luban NL. Massive transfusion in the neonate. Transfus Med Rev 1995;9:200–214. 9. Scanlon JW, Krakaur R. Hyperkalemia following exchange transfusion. J Pediatr 1980;96:108–110. 10. Estrin JA, Belani KG, Karnavas AG, et al. A new approach to massive blood transfusion during pediatric liver resection. Surgery 1986; 99:664–670. 11. Luban NL, Strauss RF, Hume HA. Commentary on the safety of red cells preserved in extended storage media for neonatal transfusions. Transfusion 1991;31:229–235. 12. Ramirez AM, Woodfield DG, Scott R, et al. High potassium levels in stored irradiated blood [letter]. Transfusion 1987;27:444–445. 13. Brugnara C, Churchill WH. Effect of irradiation on red cell cation content and transport. Transfusion 1992;32:246–252. 14. Davey RJ, McCoy NC, Yu M, et al. The effect of prestorage irradiation on posttransfusion red cell survival. Transfusion 1992;32:525–528. 15. Moore GL, Ledford ME. Effects of 4000 rad irradiation on the in vitro storage properties of packed red cells. Transfusion 1985;25:583–585. 16. Silva MA (ed). Standards for Blood Banks and Transfusion Services, 23rd ed. Bethesda, Md., American Association of Blood Banks, 2005. 17. Weiskopf RB, Schnapp S, Rouine-Rap K, et al. Extracellular potassium concentrations in red blood cell suspensions after irradiation and washing. Transfusion 2005;45:1295–1301. 18. Sandler SG, Malloy D, Malamut D, et al. IgA anaphylactic transfusion reactions. Transfus Med Rev 1995;9:1–8. 19. Sandler SG, Eckrich R, Malamut D, et al. Hemagglutination assays for diagnosis and prevention of IgA anaphylactic transfusion reactions. Blood 1994;84:2031–2035. 20. Sandler SG. How I manage patients suspected of having had an IgA anaphylactic transfusion reaction. Transfusion 2006;46:10–13. 21. Rogers RL, Javed TA, Ross RE, et al. Transfusion management of an IgA deficient patient with anti-IgA and incidental correction of IgA deficiency after allogeneic bone marrow transplantation. Am J Hematol 1998;57:326–330.

9/1/06 8:39:50 AM

Ch29-F039816.indd 417

52. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005;106:3699–3708. 53. Brecher ME (ed). Technical Manual, 15th ed. Bethesda, Md., American Association of Blood Banks, 2005, p 193. 54. Blanchette VS, Hume HA, Levy GJ, et al. Guidelines for auditing pediatric blood transfusion practices. Am J Dis Child 1991;145:787–796. 55. Brecher ME (ed). Technical Manual, 15th ed. Bethesda, Md., American Association of Blood Banks, 2005, p 804. 56. Strauss RG, Villhauer PJ, Cordle DG. A method to collect, store, and issue multiple aliquots of packed red blood cells for neonatal transfusions. Vox Sang 1995;68:77–81. 57. Personal communication. RG Strauss to SG Sandler. May 15, 2003. 58. Strauss RG, Burmeister F, Johnson K, et al. AS-1 red cells for neonatal transfusions: a randomized trial assessing donor exposure and safety. Transfusion 1996;36:873–878. 59. Sherwood WC, Clapper C, Wilson S. The concentration of AS-1 RBCs after gravity sedimentation for neonatal transfusion. Transfusion 2000;40:618–619. 60. Sandler SG, Ramasethu J. Washed and volume-reduced components. In Hillyer C, Strauss RG, Luban NL (eds). Handbook of Pediatric Transfusion Medicine. San Diego, Elsevier Academic Press, 2004, pp 113–120. 61. Skupski DW, Bussel JB. Alloimmune thrombocytopenia. Clin Obstet Gynecol 1999;42:335–348. 62. Uhrynowska M, Maslanka K, Zupanska B. Neonatal thrombocytopenia: incidence, serological and clinical observations. Am J Perinatol 1997;14:415–418. 63. McFarland JG. Platelet and neutrophil alloantigen genotyping in clinical practice. Transfus Clin Biol 1998;5:13–21. 64. Kroll H, Keifel V, Santoso S. Clinical aspects and typing of platelet alloantigens. Vox Sang 1998;74(Suppl 2):345–354. 65. Stroncek D. Neonatal alloimmune neutropenia and alloimmune thrombocytopenia. In Herman JH, Manno CS (eds). Pediatric Transfusion Therapy. Bethesda, Md., American Association of Blood Banks, 2002, pp 109–127. 66. Bussel JB, Berkowitz RL, Lynch L, et al. Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin. Am J Obstet Gynecol 1996;174:1414–1423. 67. Johnson JA, Ryan G, al-Musa A, et al. Prenatal diagnosis and management of neonatal alloimmune thrombocytopenia. Semin Perinatol 1997;1:45–52. 68. Adner MM, Fisch GR, Starobin SG, et al. Use of “compatible” platelet transfusions in treatment of congenital isoimmune thrombocytopenic purpura. N Engl J Med 1969;280:244–246. 69. Pineda AA, Zylstra VW, Clare DE, et al. Viability and functional integrity of washed platelets. Transfusion 1989;29:524–527. 70. Ranasinghe E, Walton JD, Hurd C, et al. Provision of platelet support for fetuses and neonates affected by severe fetomaternal alloimmune thrombocytopenia. Br J Haematol 2001;117:482–483. 71. Larsson L, Welsh VJ, Ladd DJ. Acute intravascular hemolysis secondary to out-of-group platelet transfusion. Transfusion 2000;40:902–906. 72. Pierce RN, Reich LM, Mayer K. Hemolysis following platelet transfusions from ABO incompatible donors. Transfusion 1985;25:60–62. 73. Josephson CD, Mullis NC, Van Demark C, et al. Significant numbers of apheresis-derived group O platelet units have “high-titer” anti-A/A,B: implications for transfusion policy. Transfusion 2004;44:805–808. 74. Schoenfeld H, Muhm M, Doepfmer U, et al. Platelet activity in washed platelet concentrates. Anesth Analg 2004;99:17–20. 75. Mustard JF, Perry DW, Ardlie N, Packham MA. Preparation of washed platelets from humans. Br J Haematol 1972;22:193–204. 76. Silvergleid AJ, Hafleigh E, Harbin M, et al. Clinical value of washedplatelet concentrates in patients with non-hemolytic transfusion reactions. Transfusion 1977;17:33–37. 77. Kalman ND, Brown DJ. Platelet washing with a blood cell processor. Transfusion 1982;22:125–127. 78. Smogorzewska A, Dzik W. Volume-reduced apheresis platelets. Transfusion 2005;45:651. 79. Schoenfeld H, Spies C, Jakob C. Volume-reduced platelet concentrates. Curr Hematol Rep 2006;5:82–88. 80. Moroff G, Friedman A, Robkin-Kline L, et al. Reduction of the volume of stored platelet concentrates for use in neonatal patients. Transfusion 1984;24:144–146. 81. Holme S, Heaton WA, Moroff G, et al. Evaluation of platelet concentrates stored for 5 days with reduced plasma volume. Transfusion 1994;34:39–43. 82. Simon TL, Sierra ER. Concentration of platelet units into small volumes. Transfusion 1984;24:173–175.

WASHED AND VOLUME-REDUCED BLOOD COMPONENTS

22. Meena-Leist CE, Fleming DR, Heye M, et al. The transfusion needs of an autologous bone marrow transplant patient with IgA deficiency. Transfusion 1999;39:457–459. 23. Sandler SG, Yu H, Rassai N. Risks of blood transfusion and their prevention. Clin Adv Hematol Oncol 2003;1:120–124. 24. Sandler SG, Silvergleid AJ (eds). Autologous Transfusion. Arlington, Va., American Association of Blood Banks, 1983, pp 1–9. 25. Kruger LM, Colbert JM. Intraoperative autologous transfusion in children undergoing spinal surgery. J Pediatr Orthop 1985;5:330–332. 26. Estrin JA, Belani KG, Karnavas AG, et al. A new approach to massive blood transfusion during pediatric liver resection. Surgery 1986;99:664–670. 27. Burman JF, Westlake AS, Davidson SJ, et al. Study of five cell salvage machines in coronary artery surgery. Transfus Med 2002;12:173–179. 28. McShane AJ, Power C, Jackson JF, et al. Autotransfusion: quality of blood prepared with a red cell processing device. Br J Anaesth 1987;59:1035–1039. 29. Yawn DH, Bull B. Intraoperative salvage: quality of products. In Maffei LM, Thurer RL (eds). Autologous Blood Transfusion: Current Issues. Arlington, Va., American Association of Blood Banks, 1988, pp 43–55. 30. Boldt J, Klind D, von Bormann B, et al. Blood conservation in cardiac operations: cell separation versus hemofiltration. J Thorac Cardiovasc Surg 1989;97:832–840. 31. Williams GD, Ramamoorthy C, Totzek FR, et al. Comparison of the effects of red cell separation and ultrafiltration on heparin concentration during pediatric cardiac surgery. J Cardiothorac Vasc Anesth 1997;11:840–844. 32. Reents W, Babin-Ebell J, Misoph MR, et al. Influence of different autotransfusion devices on the quality of salvaged blood. Ann Thorac Surg 1999;68:8–62. 33. Munoz M, Garcia-Vallejo JJ, Ruiz MD, et al. Transfusion of postoperative shed blood: laboratory characteristics and clinical utility. Eur Spine J 2004;13(Suppl 1):S107–S113. 34. Strumper EW, Weber S, Gielen-Wijffels R, et al. Clinical efficacy of postoperative autologous transfusion of filtered shed blood in hip and knee arthroplasty. Transfusion 2004;44:1567–1571. 35. De Haan J, Boonstra PW, Monnik SH, et al. Retransfusion of suctioned blood during cardiopulmonary bypass impairs hemostasis. Ann Thorac Surg 1995;59:901–907. 36. Bull BS, Bull MH. The salvaged blood syndrome. Blood Cells 1990;16:5–23. 37. Ramirez G, Romero A, Garcia-Vallejo JJ, et al. Detection and removal of fat particles from postoperative salvaged blood in orthopedic surgery. Transfusion 2002;42:66–75. 38. Van Loghem JJ, van der Hart M, Land ME: Polyagglutinability of red cells as a cause of severe haemolytic transfusion reaction. Vox Sang 1955;5:125. 39. Williams RA, Brown EF, Hurst D, et al. Transfusion of infants with activation of erythrocyte T antigen. J Pediatr 1989;115:949–953. 40. Ramasethu J, Luban NL. T activation. Br J Haematol 2001;112: 259–263. 41. Eder AF, Manno CS. Does red-cell T activation matter? Br J Haematol 2001;114:25–30. 42. Paeker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005;106:3699–3709. 43. Hillmen P, Lewis SM, Bessler M, et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med 1995;333:1253–1258. 44. Smith LJ. Paroxysmal nocturnal hemoglobinuria. Clin Lab Sci 2004;17:172–177. 45. Rosse WF, Nishimura J. Clinical manifestations of paroxysmal nocturnal hemoglobinuria: present state and future problems. Int J Hematol 2003;77:113–120. 46. Hill A, Hillmen P, Richards SJ, et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood 2005;106:2559–2565. 47. Dacie JV. Transfusion of saline-washed red cells in nocturnal haemoglobinuria (Marchiafava-Micheli disease). Clin Sci 1947;7:65. 48. Baranett EC, Dunlop JB, Pullar TH. Chronic haemolytic anemia with paroxysmal haemoglobinuria (Marchiafava syndrome): report of a case improved by splenectomy. NZ Med J 1951;50:39. 49. Hirsch J, Ungar B, Robinson JS. Paroxysmal nocturnal haemoglobinuria: an acquired dyshaemopoiesis. Aust Ann Med 1964;13:24. 50. Manchester RC. Chronic hemolytic anemia with paroxysmal hemoglobinuria. Ann Intern Med 1945;23:935. 51. Brecher ME, Taswell HF. Paroxysmal nocturnal hemoglobinuria and the transfusion of washed red cells: a myth revisited. Transfusion 1989;29:681.

29 417

9/1/06 8:39:51 AM

BLOOD BANKING

83. Strauss RG. Neonatal transfusion. In Anderson KC, Ness PM (eds). Scientific Basis of Transfusion Medicine: Implications for Clinical Practice, 2nd ed. Philadelphia, WB Saunders, 2000, pp 321–336. 84. Strauss RG, Levy GJ, Sotelo-Avila C, et al. National survey of neonatal transfusion practices. II. Blood component therapy. Pediatrics 1993;91:530–536. 85. Heddle NM, Klama L, Meyer R, et al. A randomized controlled trial comparing plasma removal with white cell reduction to prevent reactions to platelets. Transfusion 1999;39:231–238. 86. Heddle NM, Klama L, Singer J, et al. The role of the plasma from platelet concentrates in transfusion reactions. N Engl J Med 1994;331: 625–628. 87. Muylle L, Wouters E, Peetermans ME. Febrile reactions to platelet transfusion: the effect of increased interleukin 6 levels in concentrates prepared by the platelet-rich plasma method. Transfusion 1996;36:886–890. 88. Couban S, Carruthers J, Andreou P, et al. Platelet transfusions in children: results of a randomized, prospective, crossover trial of plasma removal and a prospective audit of WBC reduction. Transfusion 2002;42:753–758. 89. Vetlesen A, Mirlashari MR, Torsheim IA, Kjeldsen-Kragh J. Platelet activation and residual activation potential storage of hyperconcentrated platelet products in two different additive solutions. Transfusion 2005;45:1349–1355. 90. Allen DL, Samol J, Benjamin S, et al. Survey of the use and clinical effectiveness of HPA-1a/5b-negative platelet concentrates in proven or suspected platelet alloimmunization. Transfus Med 2004;14:409–417. 91. Dumont LJ, Krailadsiiri P, Seghatchian J, et al. Preparation and storage characteristics of white cell-reduced platelet concentrates collected by an apheresis system for transfusions in utero. Transfusion 2000;40:91–100. 92. Dumont LJ, Beddard R, Whitley P, et al. Autologous transfusion recovery of WBC-reduced high-concentration platelet concentrates. Transfusion 2002;42:1333–1339.

93. Rinder HM, Snyder EL, Tracey JB, et al. Reversibility of severe metabolic stress in stored platelets after in vitro plasma rescue or in vivo transfusion: restoration of secretory function and maintenance of platelet survival. Transfusion 2003;43:1230–1237. 94. Simon TL, Sierra ER. Concentration of platelet units into small volumes. Transfusion 1984;24:173–175. 95. Pisciotto PT, Snyder EL, Napychank PA, et al. In vitro characteristics of volume-reduced platelet concentrate stored in syringes. Transfusion 1991;31:404–408. 96. Ali AM, Warkentin TE, Bardossy L, et al. Platelet concentrates stored for 5 days in a reduced volume of plasma maintain hemostatic function and viability. Transfusion 1994;34:44–47. 97. Rock G, Haddad SA, Poon AO, et al. Reduction of plasma volume after storage of platelets in CP2D. Transfusion 1998;38:242–246. 98. Zilber M, Friedman Z, Shapiro H, et al. The effect of plasma depletion of platelet concentrates on platelet aggregation and phosphatidylserine expression. Clin Appl Thromb Hemost 2003;9:39–44. 99. Shoenfeld H, Muhm M, Doepfmer UR, et al. The functional integrity of platelets in volume-reduced platelet concentrates. Anesth Analg 2005;100:78–81. 100. Ringwald J, Walz S, Zimmermann R, et al. Hyperconcentrated platelets stored in additive solution: aspects on productivity and in vitro quality. Vox Sang 2005;89:11–18. 101. Isola H, Kientz D, Aleil B, et al. In vitro evaluation of Haemaonetics MCS+ apheresis platelet concentrates treated with photochemical pathogen inactivation following plasma volume reduction using the INTERCEPT Preparation Set. Vox Sang 2006;90:128–130. 102. Janetzko K, Lin L, Eichler H, et al. Implementation of the INTERCEPT Blood System for Platelets into routine blood bank manufacturing procedures: evaluation of apheresis platelets. Vox Sang 2004;86: 239–245. 103. Gulliksson H. Defining the optimal storage conditions for the longterm storage of platelets. Transfus Med Rev 2003;17:209–215.

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Ch29-F039816.indd 418

9/1/06 8:39:52 AM