Characterization of reactions after transfusion of cellular blood components that are white cell reduced before storage

Background: During the storage of cellular components before transfusion, cytokines that may mediate transfusion reactions are released from white cells (WBCs). Adverse effects of transfused cellular blood components therefore depend not only on the number of residual WBCs in blood components, but also on the timing of WBC reduction. Study Design and Methods: Febrile nonhemolytic transfusion reactions (FNHTRs), allergic reactions, and other reactions were characterized in recipients of 4728 units of red cells (RBCs) and 3405 bags of single-donor apheresis platelets (SDAPs), all of which underwent prestorage WBC reduction. To delineate the impact of prestorage versus poststorage WBC reduction of RBCs on transfusion reactions, these results were compared with reactions occurring after the transfusion to similar recipients of 6447 bags of RBCs that underwent poststorage WBC reduction by bedside filtration and 5197 units of SDAPs that underwent prestorage WBC reduction. The levels of interleukin (IL) 1 beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in a subset of 20 implicated cellular blood components at the time of transfusion reactions and correlated with the duration of storage before transfusion. Results: The incidence of reactions was greater after transfusions of SDAPs (5.49%) than of RBCs (1.63%). The incidence of FNHTRs after transfusion of RBCs that were WBC reduced before storage (1.1%) was significantly lower (p = 0.0045) than that after transfusion of RBCs that were WBC reduced after storage (2.15%). Although allergic reactions to RBCs that were WBC reduced before storage were also less common (0.41%) than those to RBCs that were WBC reduced after storage (0.51%), the difference was not significant (p = 0.067). At the time of reactions to RBCs and SDAPs that were reduced before storage, the level of IL-6 was negatively correlated (r = -0.54, p = 0.014) with the duration of storage before transfusion, and there was no correlation between the level of either IL-1 beta or IL-8 and the interval before transfusion. TNF-alpha was not detectable in any implicated component. Conclusion: FNHTRs, but not allergic reactions, were less common after transfusion of RBCs that were WBC reduced before storage than after the transfusion of those WBC reduced after storage at the bedside by filtration. The level of IL-6 in implicated cellular blood components that were WBC reduced before storage was inversely correlated with the length of storage before transfusion. Further studies are needed to determine whether the transfusion of cellular blood components that were WBC reduced before storage can both diminish the incidence of adverse reactions and improve outcome.     

Prestorage inline filtration of whole blood for obtaining white cell- reduced blood components

BACKGROUND: Preliminary studies have indicated that the inline filtration of whole blood is a feasible method of obtaining white cell (WBC)-reduced packaged red cells (RBCs) and WBC-reduced fresh-frozen plasma (FFP) while using only one filter. STUDY DESIGN AND METHODS: An inline WBC-reduction filter, specially designed for this purpose and integrated in a "top-top" system, was used in the preparation of 24 units of WBC-reduced RBCs (RBC-F) and FFP (FFP-F) in each of two transfusion centers (Vienna and Gottingen). Twelve conventionally prepared units of RBCs (RBC-C) and FFP (FFP-C) served as controls. WBC contamination was assessed in each unit with the Nageotte chamber. Several coagulation measures were evaluated by using standardized test systems. RESULTS: The median WBC contamination in RBC-F was 27,000 per unit in Vienna and 50,000 in Gottingen. In FFP-F, the median WBC contamination was 13,000 (Vienna) and 31,000 (Gottingen) per unit. Coagulation factors I, V, VIII, and XI in FFP-F were not different from those in FFP-C. In addition, markers for the activation of coagulation and fibrinolysis–that is, factor XIIa, prothrombin fragments, thrombin- antithrombin complexes and fibrinogen degradation products–were not greater in FFP-F. CONCLUSION: Blood components prepared from inline- filtered whole blood meet the standards for WBC-reduced RBCs and FFP. The protein profile of FFP-F is not altered, and markers for the activation of coagulation and fibrinolysis show no increase.     

Accurate quantitation of the low number of white cells in white cell- depleted blood components

A simple method of accurate quantification of low concentrations of white cells (WBCs) in WBC-depleted blood components was developed by using propidium iodide (PI) to stain the nuclei of WBCs. The method was validated by correlating the PI-determined WBC concentrations with those determined with Coulter S-plus IV counter in units of packed red cells (PRBCs) or random-donor platelets (RDPs). The correlations were linear and had coefficients of 0.99. The sensitivity of PI staining permitted the detection of concentrations of WBCs as low as 1 cell per microL of RDPs or 11 cells per microL of PRBCs. Therefore, PI staining will be useful in investigating the role of transfused WBC-depleted blood components in the prevention of primary alloimmunization to HLA antigens, as well in evaluating various new procedures with high efficiency in depleting WBCs from blood components.     

High-level long-term white blood cell microchimerism after transfusion of leukoreduced blood components to patients resuscitated after severe traumatic injury

BACKGROUND: Long-term white blood cell (WBC) microchimerism (MC), of at least 2 years, has been reported in trauma patients receiving fresh nonleukoreduced (non-LR) blood. It is unknown, however, whether this occurs with LR blood products that are nearly devoid of WBCs. Twenty-seven patients transfused with LR and non-LR blood products were studied after severe traumatic injury. A secondary aim was to explore donor-recipient mixed lymphocyte reactivity in vitro. STUDY DESIGN AND METHODS: To quantify MC, allele-specific real-time polymerase chain reaction assays were developed targeting HLA Class II sequence polymorphisms. Extensive validation showed that these assays reliably detect a single copy of target sequence in a complex allogeneic background without false positivity. RESULTS: At a median follow-up of 26 months (range, 24-39 months), long-term MC was observed in 3 of 20 patients (15%) who received non-LR blood products and 2 of 7 (29%) who received LR blood products. The maximum MC ranged from 0.40 to 4.90 percent of circulating WBCs and appeared, by Class II genotype analysis, to be attributable to a single donor. CONCLUSION: It is concluded that robust levels of long-term MC, apparently traceable to a single donor, occur at similar frequency despite leukoreduction of transfused blood products. Exploratory analysis of donor-recipient mixed lymphocyte reactivity suggests that long-term MC may require a state of bidirectional tolerance before transfusion.     

Risks associated with transfusion of cellular blood components in Canada

We provide a comprehensive review of risks associated with allogeneic red blood cell and platelet transfusions in Canada. The review focuses on clinically symptomatic noninfectious transfusion risks (acute and delayed hemolytic, febrile nonhemolytic [FNHTR], allergic, volume overload, transfusion-related acute lung injury, graft-versus-host disease, and posttransfusion purpura) and the risk of clinically significant disease from transfusion-transmitted infections. Data sources include information from Canadian Blood Services, Héma-Québec, Health Canada, and the Québec Hemovigilance System as well as published information from research studies and international hemovigilance systems. We estimate that in 2000 the aggregate risk of potentially severe reactions (excluding FNHTR and minor allergic reactions) was 43.2 per 100000 red cell units (95% confidence interval [CI]: 38.7-48.1), affecting 337 recipients, and 125.7 per 100000 platelet pools of 5 units (95% CI: 100.8-154.9), affecting 88 recipients. The most frequent potentially severe outcomes for red cell transfusion were hemolytic reactions and volume overload and for platelet transfusion were major allergic reactions and bacterial contamination. The current risk of human immunodeficiency virus and hepatitis C virus transmission is approximately 1 in 4 million and 1 in 3 million units, respectively. These estimates are useful for decisions concerning transfusion therapy, the informed consent process, and for evaluating efficacy of interventions to reduce risk.     

Rapid evaluation of risk of white particulate matter in blood components by a statewide survey of transfusion reactions

BACKGROUND: In January 2003, white particulate matter (WPM) was detected in blood components. Because the composition and cause of WPM was not understood at that time, there was uncertainty about whether WPM could endanger patient safety. To investigate possible adverse patient events associated with WPM, transfusion reaction rates were examined. STUDY DESIGN AND METHODS: A questionnaire was distributed to Georgia medical centers. Data collected included the number of components transfused and reported adverse reactions by component type from January 2002 through January 2003, and date, reaction type, and blood supplier for events in January 2003. RESULTS: Of 124 transfusion services contacted, 108 (87%) responded. During the survey period, there were 1213 reported transfusion reactions and 528,412 units transfused, or 2.3 reactions per 1000 units transfused; for RBCs, 2.4 (range, 1.8-3.1); plasma, 1.5 (range, 0.6-3.5); and PLTs, 3.4 (2.1-5.4) per 1000 units. Transfusion reaction rates by component for January 2003 did not differ significantly from the rate for January 2002 or for the calendar year. The 86 reported reactions that occurred in January 2003 were attributed to bacterial contamination (n = 2, 2.3%), other febrile nonhemolytic (n = 49, 57.0%), allergic (n = 14, 16.3%), and "other" reactions (n = 21, 24.4%); the proportions of reaction types did not differ significantly during the month. CONCLUSION: No overall changes in reported adverse reaction rates occurred over the survey period or in the proportion of reaction types during January 2003 when WPM was detected. Statewide surveillance of transfusion reactions could be useful to evaluate potential threats to blood safety.     

Febrile and allergic transfusion reactions after the transfusion of white cell-poor platelet preparations

BACKGROUND: Nonhemolytic transfusion reactions (NHTRs) frequently occur after platelet transfusions. White cell (WBC)-derived inflammatory cytokines can cause these reactions, but they are rarely found in WBC-poor platelet preparations. Transfusion reactions were investigated with regard to the residual WBC content in the stored platelet concentrate in two consecutive study periods.
STUDY DESIGN AND METHODS: In the first study period, platelet concentrates were WBC-reduced by bedside filtration. In the second period, all platelet concentrates were filtered before storage. Recipients who experienced transfusion reactions were examined with regard to their main clinical symptoms during and after transfusion. In the supernatant of the involved platelet concentrates, concentrations of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)α, macrophage inflammatory protein 1α, and RANTES were analyzed.
RESULTS: The incidence of transfusion reactions remained steady when the transfusion regimen was changed from bedside filtration to prestorage WBC filtration (1.63% and 1.56%; p = 0.84). In both periods, NHTRs were predominantly of allergic origin. Inflammatory mediators IL-1β, IL-6, IL-8, and TNFα were detectable in only a minority of platelet components involved in NHTRs. Platelet concentrates involved in allergic reactions contained high concentrations of RANTES (668 ± 223 ng/mL).
CONCLUSIONS: Prestorage WBC filtration did not reduce the incidence of these reactions, and inflammatory cytokines were of minor relevance. The proinflammatory platelet-derived chemokine RANTES, which accumulates even in WBC-reduced platelet concentrates, was associated with allergic transfusion reactions. Platelet-derived mediators may be a key to understanding NHTRs.     

Febrile and allergic transfusion reactions after the transfusion of white cell-poor platelet preparations

BACKGROUND: Nonhemolytic transfusion reactions (NHTRs) frequently occur after platelet transfusions. White cell (WBC)-derived inflammatory cytokines can cause these reactions, but they are rarely found in WBC-poor platelet preparations. Transfusion reactions were investigated with regard to the residual WBC content in the stored platelet concentrate in two consecutive study periods. STUDY DESIGN AND METHODS: In the first study period, platelet concentrates were WBC-reduced by bedside filtration. In the second period, all platelet concentrates were filtered before storage. Recipients who experienced transfusion reactions were examined with regard to their main clinical symptoms during and after transfusion. In the supernatant of the involved platelet concentrates, concentrations of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)alpha, macrophage inflammatory protein 1alpha, and RANTES were analyzed. RESULTS: The incidence of transfusion reactions remained steady when the transfusion regimen was changed from bedside filtration to prestorage WBC filtration (1.63% and 1.56%; p = 0.84). In both periods, NHTRs were predominantly of allergic origin. Inflammatory mediators IL-1beta, IL-6, IL-8, and TNFalpha were detectable in only a minority of platelet components involved in NHTRs. Platelet concentrates involved in allergic reactions contained high concentrations of RANTES (668 +/- 223 ng/mL). CONCLUSIONS: Prestorage WBC filtration did not reduce the incidence of these reactions, and inflammatory cytokines were of minor relevance. The proinflammatory platelet-derived chemokine RANTES, which accumulates even in WBC-reduced platelet concentrates, was associated with allergic transfusion reactions. Platelet-derived mediators may be a key to understanding NHTRs.     

Incidence of bacterial transmission and transfusion reactions by blood components.

Successful reduction of the risk of viral transmission via blood components has focused attention on the risk of transfusion-associated bacterial sepsis. The incidence of transfusion reactions due to bacteria is currently estimated at between 1 per 100,000 and 1 per 1,000,000 units in the case of packed red blood cells and between 1 per 900 and 1 per 100,000 units in the case of platelet concentrates. For autologous transfusion, only isolated case reports are available which do not permit a quantitative risk assessment. No reliable data on the risk of morbidity and mortality due to transfusion-associated bacterial infection are available for Germany at present. As platelet concentrates provide more favourable conditions for bacterial growth by virtue of being stored at room temperature, these blood components are thought to bear a considerably greater risk of bacterial contamination than red blood cells. The rate of contamination of platelet concentrates is cited at between 0.02% and 1.2%, depending on the production and bacterial culture techniques used, whereas the rate for packed red blood cells is between 0.1% and 0.2%. Risk reduction strategies include careful selection of blood donors, optimisation of donation and production techniques, and detection of bacteria in samples of blood components prior to transfusion. Also of importance for patient safety are quality assurance measures in the preparation for transfusion, in measures of patient monitoring, and investigation of transfusion reactions.     

Risk for postoperative infection after transfusion of white blood cell-filtered allogeneic or autologous blood components in orthopedic patients undergoing primary arthroplasty

BACKGROUND: This study was designed to obtain data on the incidence of postoperative infection in patients undergoing elective orthopedic surgery and receiving white blood cell (WBC)-filtered blood components prepared according to current standards. STUDY DESIGN AND METHODS: A total of 308 consecutive orthopedic patients who opted for preoperative autologous blood donation (PAD) for primary unilateral hip and knee replacement surgery were enrolled in a prospective observational study of the incidence of postoperative infection. Patients with contraindications for PAD or with any infectious disease were not included in the study. To identify probably confounding factors, differences between patient groups were analyzed first. Identified factors, which differed between groups, and variables describing blood supply were further tested in uni- and multivariate logistic regression analysis for their independent influence on development of postoperative infection. Infection rates were compared on the basis of actual transfusion groups. RESULTS: Of the 308 study patients, 101 were not transfused, 85 received their PAD, 100 received allogeneic WBC-filtered red blood cells (RBCs), and 22 were given autologous RBCs and additionally allogeneic WBC-filtered RBCs. Overall the infection rate was 6.82 percent (21/308). Infection rates varied significantly between transfusion groups (no transfusion, 6.9%; autologous RBCs, 1.2%; allogeneic WBC-filtered RBCs, 12.0%; both transfusion types, 4.6%; p = 0.03). Allogeneic recipients showed significantly more infections compared to autologous recipients (p = 0.0053). Multivariate regression analysis confirmed transfusion of allogeneic WBC-filtered RBCs as an independent variable predicting postoperative infection (odds ratio, 23.65; confidence interval, 1.3-422.1; p = 0.01). CONCLUSION: Differences in postoperative infection rates between allogeneic and autologous recipients are still observable, although universal WBC filtration has been introduced into clinical practice.     

A rare-event analysis model for quantifying white cells in white cell- depleted blood

An analysis model to detect and quantify white cells (WBCs) in red cell concentrates (RBCC) drawn from units of blood that are highly depleted of WBCs is described. WBC detection is performed by fluorescence analysis of 50 microL of RBCC labeled with propidium iodide, a DNA/RNA fluorophore. Quantification is performed by regression analysis of standard dilutions of RBCC in substantially WBC-free red cells. This RBCC diluent is obtained by filtration of blood through a new medium. The method proves to be precise (CV = 7%), efficient (+/- 30 min/aliquot), and linear (r = 0.99) to 6 log10 WBC depletion of the native product. The current technique is preferable to those suggested previously, such as ficoll concentration, which requires the sacrifice of the unit of blood for counting purposes, and to earlier fluorescence analysis techniques that do not employ WBC-free red cell diluents. The latter do not monitor extremely low concentrations of WBCs because they lack adequate signal-to-noise discrimination. The sensitivity of the described method allows for monitoring of WBC depletion procedures with greater efficiency than is currently available commercially.     

Safe transfusion of blood and blood components

Nurses are integral to the blood transfusion process. This article, which forms part of Nursing Standards clinical skills series, outlines the role of the nurse in evidence-based transfusion practice. Patient assessment, preparation, pre-transfusion checks, documentation and adverse reactions are discussed.     

Analysis of transfusion reactions associated with prestorage-pooled platelet components

BACKGROUND: The goal of this study was to assess transfusion reactions arising from prestorage-pooled platelet (PSPP) infusions compared with apheresis single-donor platelets (SDPs) and poststorage-pooled, whole blood–derived random-donor platelets (RDPs).
STUDY DESIGN AND METHODS: Over a span of 18 months, transfusion reaction records of patients receiving platelet (PLT) infusions were retrospectively reviewed at two academic, tertiary care hospitals. Chi-square analysis was used for statistical comparisons; significance was a p value of less than 0.05.
RESULTS: For the two sites, 10,251 prestorage-leukoreduced PLT products were infused including 4731 PSPPs, 3999 SDPs, and 1521 RDPs. Of the total infusions, 0.91% (93/10,251) were associated with a transfusion reaction. The aggregate transfusion reaction rate was 0.89% (42/4731) for PSPPs, 0.75% (30/3999) for SDPs, and 1.38% (21/1521) for RDPs. There were no significant differences in total reaction rate between PSPPs and the other PLT products (p > 0.05). Allergic transfusion reactions were the most common adverse event for PLT products evaluated (63/10,251; 0.61%) and febrile reactions were second most common (27/10,251; 0.26%). There were 2 suspected cases of sepsis (1 associated with PSPP and 1 associated with RDP; both culture negative) and 1 case of volume overload associated with RDP infusion. There were no significant differences in aggregate allergic or febrile reaction rates among the 93 PLT products evaluated (p > 0.05). No reports of transfusion-related acute lung injury or hemolysis were noted.
CONCLUSIONS: No difference in reactions rates was observed among PSPPs and the other PLT products. The transfusion reactions occurring in this population were not dependent on the type of PLT product infused.     

Survival after blood transfusion

BACKGROUND: Long‐term survival of transfusion recipients has rarely been studied. This study examines short‐ and long‐term mortality among transfusion recipients and reports these as absolute rates and rates relative to the general population. STUDY DESIGN AND METHODS: Population‐based cohort study of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all‐cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first registered transfusion. Three months after the first transfusion, 84.3 percent of recipients were alive. One‐, 5‐, and 20‐year posttransfusion survival was 73.7, 53.4, and 27.0 percent, respectively. Survival was slightly poorer in men than in women, decreased with increasing age, and was worst for recipients transfused at departments of internal medicine. The first 3 months after the first transfusion, the standardized mortality ratio (SMR) was 17.6 times higher in transfusion recipients than in the general population. One to 4 years after first transfusion, the SMR was 2.1 and even after 17 years the SMR remained significantly 1.3‐fold increased. CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion‐transmitted disease as well as for cost‐benefit estimation of new blood safety interventions.