C1q-Binding HLA Antibodies Do Not Predict Platelet Transfusion Failure in TRAP Study Participant

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1562-1562
Author(s):  
Rachael P. Jackman ◽  
Douglas Bolgiano ◽  
Mila Lebedeva ◽  
Sherrill J. Slichter ◽  
Philip J. Norris
Keyword(s):  
Conflicts Of Interest ◽  
Fluorescent Antibody ◽  
Study Participant ◽  
Class I ◽  
Detection Methods ◽  
Antibody Detection ◽  
Hla Antibodies ◽  
Luminex Assay ◽  
Single Antigen ◽  
Antibody Levels

Abstract Introduction: In the Trial to Reduce Alloimmunization to Platelets (TRAP) study, 101 of the 530 subjects became clinically refractory (CR) to platelet transfusions in the absence of detectable antibodies against HLA as measured by the lymphocytotoxicity assay (LCA). Using more sensitive bead-based detection methods we have previously demonstrated that while many of these LCA- patients do have anti-HLA antibodies, that these low to moderate level antibodies do not predict refractoriness. In addition to being less sensitive then bead based methods, the LCA screen only detects complement-binding antibodies. As these antibodies could be important for platelet rejection, we assessed if previously undetected complement-binding antibodies could account for some of the refractoriness seen in LCA- patients. Methods: 169 LCA- (69 CR, 100 non-CR) and 20 LCA+ (10 CR, 10 non-CR) subjects were selected from the TRAP study. Anti-class I HLA IgG and C1q binding antibodies were measured in serum or plasma using two different multi-analyte, semi-quantitative, bead-based fluorescent antibody detection assays: the LabScreen mixed Luminex assay, and the LabScreen single antigen class I assay with or without added EDTA (One Lambda). Groups were compared using an unpaired t-test, a=0.05, and correlation between variables was also assessed. Results: New measurements of anti-class I HLA IgG antibodies reliably reproduced earlier data with a strong correlation between the old and new measurements (R2=0.9736, p<0.0001). While some of the LCA- subjects did have detectable C1q-binding anti-class I HLA antibodies, and some LCA+ subjects did not, levels of these antibodies were significantly higher among LCA+ subjects (p<0.0001). Levels of C1q-binding anti-class I HLA antibodies were not significantly different between CR and non-CR among either the LCA- or LCA+ subjects. Conclusions: While complement-binding anti-class I HLA antibody levels were higher in the LCA+ subjects, higher levels of these antibodies were not seen in CR LCA+ patients as compared with non-CR LCA+ patients. Complement-binding anti-class I HLA antibodies do not account for refractoriness seen among the LCA- TRAP subjects. This work confirms that low to mid level anti-class I antibodies do not drive refractoriness to platelets, and suggests that antibody-independent mechanisms cause refractoriness in patients lacking higher levels of anti-HLA antibodies. Disclosures No relevant conflicts of interest to declare.

Prevalence and Significance of Pre-Formed Anti-HLA Antibodies in Hematopoietic Stem Cell Transplant Recipients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1174-1174
Author(s):  
Darshan Gautam Gandhi ◽  
Jennifer Holter ◽  
Mohamad Khawandanah ◽  
Robert B. Epstein ◽  
Julie Stoner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Failure ◽  
Hla Antigens ◽  
Class Ii ◽  
Class I ◽  
Hla Antibodies ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Antibody Levels

Abstract Abstract 1174 Poster Board I-196 Introduction: The presence of sensitization to HLA antigens has been an important consideration in solid organ transplantation. It is considered a standard process to check for donor-specific allogeneic (allo) antibodies (DSA) and monitor formation of such antibodies post-transplant which could predict early and late graft failure. Most of the current data regarding the importance of anti-HLA (human leukocyte antigen) antibodies is available from renal transplant where presence of HLA antibodies is clearly associated with an increased risk of early graft loss up to the magnitude of 21%. It is routine to perform desensitization to alleviate these antibodies in an effort to enhance their chances of engraftment. The role of and approach to prior sensitization in the hematopoietic stem cell transplantation (HSC) setting is far less clear. This is of unique importance as a wider range of donor cell sources and transplant applications are utilized to treat hematologic diseases. Many of our patients have had multiple transfusions in the past, been pregnant or have had prior HLA mismatched allograft, all of which predispose to development of anti-HLA antibodies. Here we analyze the prevalence of Class I and Class II antibodies as a primary goal and also see if they correlate with graft survival. Methods: 52 patients were followed between July 2008 and July 2009 with hematologic malignancies including leukemia's, lymphoma's, multiple myeloma and others. 37/52 underwent transplantation of which 14 were unrelated donor (URD), 5 cord blood (CB) and 8 sibling (sib) transplants. Donors with corresponding HLA were excluded. Post-transplantation with day 100 antibody testing was performed in eligible patients. Antibody determination was done by testing the patients' sera with a panel of fluorescent beads coated with single HLA antigens using a solid-phase Luminex™ platform. Cut-point of 1500 [mean fluorescence intensity (MFI) ≥ 1500 defined as positive] was used for performing statistical analyses. The prevalence of positive antibody levels was compared among the transplant groups using a Fisher's exact test. Level of expression of antibodies was evaluated with MFI <500 considered negative, 500-1500 weak, 1500-3000 intermediate and >3000 strong. High resolution HLA typing was performed. Results: Class I antibodies were positive in 24 out of 52 total (46%) with 95% CI: 32% to 61%.14/37 (38%) who underwent transplantation (95% CI: 22% to 55%), 12/27 (44%) undergoing allo transplant, CB (20%), sib (38%), and URD (57%) were positive. The prevalence did not differ significantly among the transplant groups (p=0.3). Class II antibodies were positive in 8 out of 52 total (15%) with 95% CI: 7% to 28%. 5/37 (14%) who underwent transplantation (95% CI: 5% to 29%), 4/27 (15%) undergoing allo transplant, Sib (0%), CB (20%) and URD (21%) were positive. The prevalence did not differ significantly among the transplant groups (p=0.6). In females, 18/28 (64%) were positive for Class I or Class II antibodies of which 5/6 (83%) underwent URD transplants. Persistent antibody levels were detected in 3 of 4 patients tested at day 100 post transplant. Conclusions: Based on this limited pilot study we conclude that there is a high prevalence of anti-HLA antibodies present in recipients at the time of HSC transplantation. However detection of such antibodies did not jeopardize engraftment from various donor sources when HLA donor specific reactions are excluded. Bray et al showed higher incidence of graft failure associated with DSA. Takanashi et al showed that in CB transplants, antibodies were not significant unless the corresponding HLA was present in the CB unit. Based on these studies, we excluded donors with corresponding HLA. All but one patient, in whom donor specific anti-HLA antibodies were identified, achieved sustained marrow engraftment. The long term implications of antibody evolution and specificity to sustained marrow engraftment, graft vs. host and graft vs. tumor effects remain to be clarified. A larger prospective study will need to be conducted to definitely evaluate these relationships including our own which is currently under way. Disclosures: No relevant conflicts of interest to declare.

DynaChip Anti-HLA Antibody Analysis In Sera of Patients Following Allo-HSCT From HLA-Mismatched Unrelated Donors.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4575-4575
Author(s):  
Miroslaw Markiewicz ◽  
Urszula Siekiera ◽  
Tomasz Kruzel ◽  
Monika Dzierzak-Mietla ◽  
Patrycja Zielinska ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Hla Class I ◽  
Class I ◽  
Hla Antibodies ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Study Results ◽  
Reactive Groups ◽  
Unrelated Donors ◽  
Class Ii Antigens

Abstract Abstract 4575 Introduction: Anti-HLA antibodies constitute potentially important factor that may influence outcomes of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT). The rationale of this study was to detect presence of anti-HLA antibodies in recipients of allo-HSCT from HLA-mismatched unrelated donors. Patients and Methods: Anti-HLA-A,B,C,DR,DQ,DP antibodies were identified in sera collected from 46 recipients of allo-HSCT from HLA-mismatched unrelated donors. Sera were collected between 1 month and 5.5 years after allo-HSCT, and additionally before allo-HSCT in 17 pts. We have used microchips spotted with purified HLA class I and HLA class II antigens to allow binding of anti-HLA antibodies present in tested sera to the surface of the microchip, pre-optimised reagents and DynaChip Processor (Dynal Invitrogen Corporation) for assay processing, data acquisition and analysis. Results: Antibodies against HLA class I, II or I and II were detected in 15%, 11% and 35% of pts whereas no antibodies were detected in 39% of patients. Antibodies were directed against HLA-A, B, C, DR and DQ in 37%, 46%, 35%, 48% and 35% of pts, respectively. Pre-transplant anti-HLA antibodies have been detected in 7 pts (41%) out of 17 tested before allo-HSCT. In this group percent of Panel Reactive Antibodies (% PRA) increased following allo-HSCT in 3 pts and decreased in 4. In 5 out of 10 remaining pts without pre-transplant antibodies, %PRA increased post-transplant. DynaChip software allowed to define specificities of HLA-A,B,C,DR and DQ antibodies on low and high resolution levels. The specificity of antigens that masked results of antibody identification has been also defined in 2 pts. At this stage we did not define exactly whether detected anti-HLA antibodies were donor-specific. Cross-reactive groups (CREG's) analysis has been also used to compare antibodies’ reactivity. Anti-HLA-DP antibodies were not detected in the examined group of transplanted patients. Conclusions: Presented preliminary study results indicate, that anti-HLA antibodies can appear post-transplant in mismatched allo-HSCT recipients. Further analysis aiming to evaluate their influence on transplant outcomes is ongoing. We intend to extend the search for anti-HLA antibodies with use of Luminex LabScreen method. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Generation of iPSC-Derived Human Megakaryocytes for Flow Cytometric Detection of Platelet-Specific Alloantibodies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 740-740
Author(s):  
Nanyan Zhang ◽  
Peter Newman
Keyword(s):  
Conflicts Of Interest ◽  
Flow Cytometric Analysis ◽  
Hla Class I ◽  
Blood Type ◽  
Class I ◽  
Antibody Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transfusion Therapy ◽  
Flow Cytometric ◽  
Simple Flow

Abstract Antibodies that form against human platelet alloantigens (HPAs) are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia, posttransfusion purpura, and multitransfusion platelet refractoriness. Some of HPAs are relatively rare in the population, and difficult to obtain for purposes of transfusion therapy and diagnostic testing. In addition, HPA alloantisera often contain antibodies against human leucocyte antigen (HLA) class I, thereby limiting antibody detection to glycoprotein (GP)-specific assays such as the modified antigen capture enzyme-linked immunosorbent assay (MACE) and the monoclonal immobilization of platelet antigen (MAIPA), which are tedious and require solubilization of platelet GPs that may cause the loss of epitopes. In this study we aimed to generate gene-edited, HPA-specific, megakaryocytes (MKs) derived from human induced pluripotent stem cells (iPSCs) that could be used for simple flow cytometric detection of specific HPA alloantibodies present in patient sera. The HPA-3a/HPA-3b alloantigen system, also known as Baka/Bakb, is caused by a single T13809G nucleotide substitution in the ITGA2B gene, resulting in an Ile874Ser amino acid polymorphism near the C terminus of the integrin αIIb subunit (GPIIb). Here we targeted HPA-3 system because alloantibodies targeting HPA-3 are often hard to detect with current detection methods, in part due to the requirement for cell type-specific glycosylation. To prevent interference of anti-A or anti-B antibodies in patient sera, a blood type O iPSC line (OT1-1) was generated from human peripheral blood mononuclear cells derived from a healthy donor using integration-free episomal vectors. The gene for β2 microglobulin (B2M) was first ablated from the OT1-1 iPS cell line using CRISPR/Cas9 to prevent binding of HLA class I alloantibodies. The resulting B2M knockout (B2MKO) cells were then additionally gene edited to convert the endogenous HPA-3a alloantigenic epitope present on B2MKO OT1-1 cells to HPA-3b. Two different guide RNAs targeting sequences that flank exon 26 of the ITGA2B gene were designed such that the entire exon harboring the HPA-3 polymorphic site was removed. A plasmid harboring a template replacing exon 26 with the G13809 mutation, flanked by 600 bp homology arms, was cotransfected into the B2MKO OT1-1 iPSCs together with the two CRISPR/Cas9 guide RNA constructs. iPSC clones containing the desired targeted T13809G mutation were identified by a diagnostic MfeI digestion specific for the G13089-bearing HPA-3b allele. Sequence analysis confirmed conversion of T13089 to G in these HPA-3b clones. Flow cytometric analysis showed the HPA-3a iPSCs, when differentiated into CD41+/CD42b+ MKs, specifically reacted with HPA-3a, but not HPA-3b, patient sera, while the HPA-3b iPSC-derived MKs lost reactivity with HPA-3a patient serum, and gained the reactivity with HPA-3b patient sera. Taken together, we have established genetically modified iPSC-derived MKs expressing specific HPAs that are suitable for simple flow cytometry-based detection of HPA alloantibodies in patient sera, with low non-specific background binding. This system provides intact antigens on the cell surface with carbohydrate moieties that likely mimic those found on human platelets, thus facilitating the detection of HPA alloantibodies that are normally hard to detect with current methods. Application of this strategy to genetically edit this and other clinically-important HPAs holds great potential for producing Designer Platelets for diagnostic, investigative and ultimately therapeutic use. Disclosures No relevant conflicts of interest to declare.

Heparin-Induced Thrombocytopenia: Comparison Between the Standard Gel-Particle Assay (PaGIA) and the Functional Flow Cytometric Assay.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5060-5060
Author(s):  
Aaron Tomer
Keyword(s):  
Conflicts Of Interest ◽  
Multiorgan Failure ◽  
Relative Sensitivity ◽  
Serotonin Release ◽  
Detection Methods ◽  
Antibody Detection ◽  
Flow Cytometric Assay ◽  
Heparin Induced Thrombocytopenia ◽  
Flow Cytometric ◽  
Relative Specificity

Abstract 5060 Background Heparin-induced thrombocytopenia and thrombosis (HIT) is an immune-mediated complication that may develop in patients sensitized to heparin. Approximately 5% of patients treated with full dose heparin develop clinical HIT, with about half develop thrombosis that may be associated with severe morbidity and death. However, antibodies may be detected in up to 30% of patients. Thus, current antibody-detection methods carry certain limitations, which pose a serious clinical dilemma in the diagnosis and treatment of HIT. Objectives To compare the gel-particle immuno-assay (PaGIA) for the detection of antibodies against heparin-PF4 complex, with the functional flow cytometric assay (FCA) which determines the capacity of the patient's serum to activate platelets in the presence of heparin, similar in concept to the gold-standard, the radioactive Serotonin-release assay. Methods Sequential samples from patients clinically suspected for HIT were tested by both PaGIA and the FCA (Tomer 1997, 1999). Results 118 samples were tested. Positive: 9 (7.6%) patients tested positive by PaGIA, compared to 19 (16.1%) by the FCA. 7,out of the 9 (77.8%) PaGIA -positive samples were also positive by the FCA (relative sensitivity). Negative: 97 out of 109 gel-negative samples (89.0%) were also negative by the FCA (relative specificity). Thrombosis occurred in 3 of the 9 PaGIA-positive (33%) patients, and in 7 of the 19 FCA-positive (36.8%) patients. Of the 12 PaGIA -negative but FCA-positive patients, 4 (33%) had thrombosis. Death rate was also higher among FCA-positive (n=3) compared to PaGIA-positive (n=1) patients. Of the two PaGIA -positive but FCA-negative patients, one had APLA syndrome (APS) with chronic thrombocytopenia, and one had sepsis with cardiogenic shock and multiorgan failure. ROC-Plot: Overall, the FCA showed significantly higher correlation with the clinical presentation of HIT (4Ts score), compared to the PaGIA (AUC 0.86 vs. 0.62, p<0.001) Conclusion The functional FCA demonstrates superior sensitivity and specificity compared to the antibody- detection PaGIA gel-particle assay. The feasible functional FCA (results in 1.5 hr) might be useful for initial diagnosis of HIT, and particularly for confirmation of HIT in patients with confounding presentation, including negative antibody-detection assay. Disclosures No relevant conflicts of interest to declare.

Antibody Monitoring System to Support the Single-Antigen Luminex Assay in Donor-Specific Antibody Detection

2012 ◽  
Vol 94 (10S) ◽  
pp. 1164
Author(s):  
H. S. Hwang ◽  
S. Y. Kim ◽  
H. E. Yoon ◽  
B. H. Chung ◽  
B. S. Choi ◽  
...  
Keyword(s):  
Monitoring System ◽  
Specific Antibody ◽  
Antibody Detection ◽  
Luminex Assay ◽  
Single Antigen

scholarly journals Anti-HLA Antibodies in Neonatal Alloimmune Thrombocytopenia - Is There Any Clinical Significance?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4647-4647 ◽  
Author(s):  
Lilach Bonstein ◽  
Nardeen Atweh ◽  
Nuhad Haddad ◽  
Yariv Fruchtman
Keyword(s):  
Platelet Count ◽  
Antibody Titer ◽  
Conflicts Of Interest ◽  
Hla Class I ◽  
Class I ◽  
Hla Antibodies ◽  
Neonatal Thrombocytopenia ◽  
Alloimmune Thrombocytopenia ◽  
Sample Case ◽  
Hla Antibody

Abstract Background: Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal alloantibodies raised against paternally inherited alloantigens carried on fetal platelets. Platelets express both HLA class I and specific human platelet antigens (HPA). Although anti-HLA class I antibodies are often detectable in pregnant women, NAIT is considered to be mainly associated with antibodies against HPA. Cases where NAIT has been caused by antibodies against HLA class I are relatively rare and the role of these antibodies in NAIT remains debatable. We hereby describe a sample case of NAIT proved to be caused solely by anti-HLA antibodies and discuss laboratory measures aimed at identification of pregnancies at risk of NAIT related to anti-HLA class I antibodies based on a series of similar cases. Methods: This sample case presents laboratory work-up on a young mother who delivered her first son with a platelet count of 20x109/L, minor petechiae and normal WBC count. Thrombocytopenia in the newborn resolved spontaneously two weeks after birth. Laboratory investigation included platelet immunofluorescence test (PIFT), monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, genotyping of both parents and the newborn for platelet antigens, including rare antigens, and HLA antibody identification using the panel reactive antibodies (PRA) assay (Luminex, USA). A serum sample of this mother, drawn during her second pregnancy, and those of ten other women referred to our laboratory with a similar obstetric history of neonatal thrombocytopenia, were evaluated for the anti-HLA antibody titer using the MAIPA assay. Results: The Rambam Platelet & Neutrophil Immunology Laboratory, as well as 32 other laboratories worldwide, that participated in the 2014 International Workshop organized by the ISBT Platelet Immunobiology Working Party failed to detect anti-HPA antibodies in the mother's serum during her second pregnancy, despite using the most sensitive serological analysis and molecular methods. Only strong anti-HLA antibodies with no single specificity were found in the analyzed samples by all the laboratories. Her second child was born by caesarean section with a platelet count of 50x109/L and maternal anti-HLA antibodies were found in his serum and on his platelets. The anti-HLA antibody titer of the mother, determined by the MAIPA assay, was greater than 1:1024, with antibodies being multi-specific, as demonstrated by PRA. The anti-HLA antibody titer ≥1:16 was found to correlate with low platelet counts in the additional ten cases tested, as opposed to the titer of ≤1:4 in cases with mild and not clinically significant neonatal thrombocytopenia. Conclusions: The presence of anti-HLA class I antibodies should be considered as a potential cause of NAIT, especially in cases with a very high titer of antibodies. The mechanism underlying the effect of these antibodies on fetal platelets needs to be further investigated. Disclosures No relevant conflicts of interest to declare.

On the Detection of Anti-HLA Antibodies Using Single Antigen Bead Luminex Assay

2013 ◽  
Vol 96 (4) ◽  
pp. e24-e26 ◽  
Author(s):  
Rex Friedlander ◽  
Prabhakar Putheti ◽  
Elder Diaz ◽  
Arvind Menon ◽  
Blanca Ponce ◽  
...  
Keyword(s):  
Hla Antibodies ◽  
Luminex Assay ◽  
Single Antigen

30-P: Technical Variation in HLA Antibody Levels Measured by Single Antigen Luminex Assay is Directly Proportional to Total Bound Antibody

2010 ◽  
Vol 71 ◽  
pp. S39
Author(s):  
Christian P. Larsen ◽  
Phillip J. Summers ◽  
Aaron T. Whiteley ◽  
Lee Ann Baxter-Lowe
Keyword(s):  
Luminex Assay ◽  
Single Antigen ◽  
Antibody Levels ◽  
Hla Antibody

A Fully-Automated Screening Method for Anti-HLA Antibodies: Implications for Screening Plasma Donations To Prevent Transfusion-Related Acute Lung Injury (TRALI).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 959-959
Author(s):  
Elizabeth Culler ◽  
Sheilagh B. Barclay ◽  
Robert A. Bray ◽  
Howard M. Gebel ◽  
Christopher D. Hillyer ◽  
...  
Keyword(s):  
Hla Class I ◽  
Class I ◽  
Antibody Detection ◽  
Additional Patient ◽  
Hla Antibodies ◽  
Automated Method ◽  
Automated Screening ◽  
Negative Controls ◽  
Hla Antibody ◽  
Donor Plasma

Abstract Background: TRALI is a potentially fatal complication of transfusion. Although the pathogenesis is not completely understood, and may involve a “multi-hit” mechanism, transfusion of donor plasma containing anti-HLA and/or anti-neutrophil antibodies appears to play an important role. In previous studies, up to 22% of all blood components were found to contain HLA antibodies (Bray et al, Human Immunology, 65, 240–4, 2004). Based on the possible involvement of HLA antibodies in TRALI, some blood services no longer provide plasma from female donors for transfusion, since these donors are more likely to have these antibodies due to pregnancy. An alternative, more specific approach to prevent transfusion of HLA antibody-containing plasma, and possibly reduce the risk of TRALI, is to screen plasma prior transfusion. However, no automated method is yet available with sufficient throughput to screen blood donors for HLA antibodies. Methods: The 3Ti Aegis is a novel open-architecture automated blood typing platform that uses fluorescence cytometry. The Aegis was readily configured for detecting anti-HLA Class I antibodies in donor plasma by modifying the commercially-available FlowPRA Class I Screening Test (One Lambda, Canoga Park, CA) to include a phycoerythrin (PE)-labeled secondary antibody. Positive and negative control samples, as well as patient specimens previously demonstrated to contain HLA antibodies, were evaluated to determine the accuracy of the automated Aegis method. Results: Positive and negative controls were readily distinguished from one another whether testing was performed manually (according to manufacturer’s instructions) and acquired on a BD FACScan cytometer, or performed using the fully-automated method on the 3Ti Aegis. For the Aegis, the mean fluorescence intensities for positive and negative controls were 156.2 and 14.4, respectively. For the manual method, the signal to noise separation was comparable (692.5 and 28.9, respectively). Six additional patient samples, which had previously identified anti-Class I antibodies, also tested positive with the Aegis system. Estimated staining and acquisition times on the Aegis for 96 samples are 2 hours and 1.5 hours, respectively, which is comparable to the times for manual testing Conclusions: The Aegis can perform accurate, high throughput, completely automated screening of plasma donations for HLA Class I antibodies prior to transfusion. Future work will focus on developing combined Class I and II screening beads, as well as beads for detecting common anti-neutrophil antibodies, to produce a comprehensive TRALI antibody detection package for the Aegis platform. The Aegis is the first device to make pretransfusion HLA antibody testing practical, and may reduce the incidence of TRALI and accompanying transfusion fatalities.

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