bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients with neoplastic and nonneoplastic hematologic diseases acquire CTLA‐4 antibodies after blood transfusion
Authors: Pistillo Maria Pia , Tazzari Pier Luigi , Gaudiano Carlo , Cilla Vito , Kato Tomohiro , Matsui Toshihiro , Nishioka Kusuki , Capanni Paolo , Conte Roberto , Ferrara Giovanni Battista 
Published: March 2003

BACKGROUND: The presence of antibodies to CTLA‐4, a negative regulator of T‐cell activation, was investigated in multiply transfused patients with malignant and non‐ malignant hematologic diseases. A previous study showed that, in multiply transfused patients, an immune response against nuclear matrix proteins can be induced by WBCs undergoing apoptosis during RBC unit storage. This study evaluated whether the same phenomenon could be involved in the induction of CTLA‐4 antibodies in the patients analyzed.STUDY DESIGN AND METHODS: Patient sera were tested for binding to the recombinant full‐length CTLA‐4 β‐galactosidase fusion protein by an ELISA. Immuno‐fluorescence stainings were performed to analyze the CTLA‐4 epitopes recognized by the antibodies and to detect such epitopes in the apoptotic cells present in the RBC units.RESULTS: CTLA‐4 antibodies were found in multiply transfused patients with β‐thalassemia (40%) and with other hemolytic diseases (33%) including leukemias (42%). A higher incidence of CTLA‐4 antibodies was found in patients receiving non‐WBC‐reduced blood (88%) than in those receiving WBC‐reduced blood (26%). Immunofluorescence staining showed that WBCs undergoing apoptosis in the RBC unit expressed CTLA‐4 epitopes.CONCLUSIONS: The apoptotic WBCs present in the RBC units, after cold storage, express CTLA‐4 epitopes. These epitopes can be released and induce formation of CTLA‐4 antibodies with profound implications in the development of autoimmune disorders and in facilitating tumor dissemination and metastasis.
Evaluation of a whole‐blood WBC‐reduction filter that saves platelets: in vitro studies
Authors: Larsson Stella , Gulliksson Hans , Paunovic Dragica 
Published: March 2003

BACKGROUND: In this study, a new WBC‐reduction in‐line filter that removes WBCs but not platelets was evaluated. Three WBC‐reduced blood components were prepared: RBCs, plasma, and platelet concentrates (PCs).STUDY DESIGN AND METHODS: Whole‐blood components (n = 30) were filtered within 2 to 4 hours after collection and then were centrifuged and separated into RBCs, plasma, and WBC‐reduced buffy coat. Saline‐adenine‐glucose‐mannitol solution was added to the RBCs. The WBC‐reduced buffy coats were stored overnight; on the following day, PCs were prepared from pooled WBC‐reduced buffy coats and stored in a medium composed of approximately 35 percent CPD plasma and 65 percent platelet additive solution (T‐Sol, Baxter). The WBC‐reduction capacity of the filter, the recovery of cells after filtration, and the in vitro storage of RBCs (n = 10) and platelets (n = 6) were evaluated.RESULTS: Mean and maximum WBC counts after filtration were 0.08 × 106 and 0.3 × 106, respectively, per filtered whole‐blood unit. Recovery of RBCs (mean values) after filtration was 90 percent in whole‐blood components and 73 percent in RBCs. Recovery of platelets (mean values) was 81 percent after filtration and 66 percent in PCs. The in vitro storage study of RBCs showed results comparable with previously published data, except for a lower degree of hemolysis. In the in vitro platelet storage study, results were compared with those of standard preparations. In all essentials, similar results were found.CONCLUSION: The results of the present study suggest that effective WBC reduction meets current standards and satisfactory recovery after filtration. The storage characteristics for RBCs and PCs are similar to those of standard preparations. Use of a whole‐blood in‐line filter to save platelets is a new option for whole‐blood processing, which may simplify WBC reduction and blood component preparation, as well as reduce costs in the future.
Influence of temperature, filter wettability, and timing of filtration on the removal of WBCs from RBC concentrates
Authors: Van Der Meer Pieter F. , Pietersz Ruby N.I. , Reesink Hendrik W. 
Published: March 2003

BACKGROUND: The efficacy of the removal of WBCs from buffy coat‐reduced RBC concentrates by filtration is determined by many variables. The aim of this study was to investigate the influence of the filtration temperature, the wettability of the filter material, and the timing of the filtration after collection.STUDY DESIGN AND METHODS: The investigation used commercially available filters: 3 dry “online” filters (Cellselect FR, Fresenius Hemocare; BioR‐01‐max, Fresenius; Leucoflex LCG1, MacoPharma) and one wet “inline” filter (Leucoflex LCR4, MacoPharma) that contained saline‐adenine‐glucose‐mannitol additive solution for RBCs and differed from the online version only in wettability. After buffy coat removal and suspension in saline‐adenine‐glucose‐mannitol, filtrations were performed immediately at room temperature (RT) and after 2 hours' storage of the RBC concentrates at 4°C, while the Leucoflex LCR4 was also tested after 24 hours' storage of the RBC concentrates at 4°C. Sets of 12 pooled experiments were performed to prevent donor‐dependent differences.RESULTS: The Cellselect FR gave significantly better WBC removal from RBC concentrates at 4°C than at RT, with residual WBCs of 1.44 ± 0.58 × 106 and 2.78 ± 1.23 × 106, respectively (p<0.001). The BioR‐01‐max gave no significant difference: 0.62 ± 0.27 × 106 WBCs (at 4°C) versus 0.61 ± 0.25 × 106 WBCs (at RT). Filtration with the Leucoflex LCG1 resulted in 0.06 ± 0.03 × 106 and 0.07 ± 0.07 × 106 WBCs at 4°C and RT, respectively, which is not a significant difference. The Leucoflex LCR4, however, gave 2.08 ± 0.84 × 106 WBCs at RT, 0.52 ± 0.44 × 106 WBCs at 4°C after 2 hours' cooling, and 0.05 ± 0.10 × 106 WBCs at 4°C after 24 hours' cooling (all p<0.001).CONCLUSION: Temperature, filter wettability, and timing of filtration after collection influence the efficacy of a filter for RBC concentrates. These variables need to be established, validated, and controlled before a filter can be selected for routine use.
IL‐10 increases the number of CFU–GM generatedby ex vivo expansion of unmanipulated human MNCsand selected CD34+ cells
Authors: Wagner Thomas , Fritsch Gerhard , Thalhammer Renate , Höcker Paul , Lanzer Gerhard , Lechner Klaus , Geissler Klaus 
Published: March 2003

BACKGROUND: Ex vivo expansion strategies with different cytokine combinations are currently used by several groups as a means of increasing the number of HPCs for a variety of special clinical applications. Because there is little information on the potential role of IL‐10 in such ex vivo expansion models, the effect of this cytokine on the generation of myeloid progenitor cells in suspension cultures was investigated.STUDY DESIGN AND METHODS: On the basis of data from the literature and from new experiments, the combination of SCF and IL‐3 at concentrations of 100 ng per mL and 100 U per mL, respectively, was chosen as the standard cocktail. The addition of IL‐10 to such cultures resulted in a marked and dose‐dependent potentiation of myeloid progenitor cell production.RESULTS: Using unmanipulated leukapheresis components from 13 individuals (including lymphoma and cancer patients and normal donors), the expansion multiple of CFU–GM after 14 days as compared with pre‐expansion values was 9.54 ± 2.31 times by SCF/IL‐3 and 46.38 ± 7.37 times by the combination of SCF/IL‐3 and 100 ng per mL of IL‐10 (p<0.001). IL‐10 also potentiated CFU–GM generation from selected CD34 PBMNCs (n = 9) with an expansion of 17.22 ± 7.04 times versus 45.67 ± 16.78 times using the SCF/IL‐3 and SCF/IL‐3/IL‐10 combination, respectively (p<0.05). Moreover, expansion‐promoting effects of IL‐10 were observed in liquid cultures containing MNCs from bone marrow (n = 4) and cord blood (n = 3), but did not reach statistical significance because of the small number of samples.CONCLUSION: These results suggest IL‐10 as a useful cytokine to optimize progenitor cell‐expansion strategies for clinical application.
Determinants of transfusion‐associated bacterial contamination: results of the French Bacthem Case‐Control Study
Authors: Perez Paul , Salmi L. Rachid , Folléa Gilles , Schmit Jean‐Luc , De Barbeyrac Bertille , Sudre Philippe , Salamon Roger ,   for the Bacthem Group the French Haemovigilance Network
Published: March 2003

BACKGROUND : Transfusion‐associated bacterial contamination (TABC), probably the most frequent transfusion‐transmitted infection, may induce serious adverse events. Systematic information and documentation on determinants are lacking.STUDY DESIGN AND METHODS : The Bacthem Study is a French matched case‐control study assessing TABC determinants. Included were cases of TABC reported in France in a 2‐year period, as determined from uniform definitions. Information on recipient‐, blood component‐, and donor‐related potential determinants was collected on site. ORs were estimated by conditional logistic regression.RESULTS : Of the 158 cases of suspected TABC reported, 41 that involved transfusion with 25 RBCs and 16 platelet concentrates were included. Gram‐negative rods accounted for nearly half of the bacteria species involved and for all six deaths. In comparison with the risk of TABC for patients receiving RBCs for anemia, the risk was higher for patients receiving RBCs for pancytopenia (OR, 7.3; 95% CI, 1.3‐41.0) and for those receiving platelets for thrombocytopenia (OR, 5.3; 95% CI, 1.2‐24.1). Other potential determinants were platelet transfusion for pancytopenia (OR, 4.5; 95% CI, 0.5‐40.0), immunosuppressive treatment (OR, 2.8; 95% CI, 0.7‐10.6), shelf‐life of more than 1 day for platelets or 8 days for RBCs (OR, 2.6; 95% CI, 0.7‐9.6), and more than 20 previous donations by donors (OR, 1.9; 95% CI, 0.7‐5.3).CONCLUSION : This first comparative study revealed TABC determinants that suggest approaches for prevention.
Changes in immunologic properties of group A RBCs during treatment with an A‐degrading exo‐α‐N‐acetylgalactosaminidase
Authors: Hoskins Lansing C. , Boulding Erwin T. 
Published: March 2003

BACKGROUND: Blood group A RBCs theoretically can be converted to universal‐donor group O cells by incubation with α‐N‐acetylgalactosaminidase (A‐zyme). The purpose of this study was to compare the extent of A‐zyme treatment required to abolish several immunologic responses of group B or O recipients to group A RBCs.STUDY DESIGN AND METHODS: A1 RBCs were incubated for 2 hours at 37°C in buffer alone (control) or with 0.1 to 5.0 units (U) of A‐zyme per mL of packed cells. They were then tested for 1) immune adherence (% rosetting) and activation of monocytic cells (% erythrophagocytosis, TNFα production), 2) activation of immune hemolysis, and 3) hemagglutination with Dolichos biflorus lectin and pooled human anti‐A serum.RESULTS: A 2‐hour incubation with ≤5.0 U of A‐zyme per mL of packed cells abolished monocytic cell adherence and phagocytosis of group A1 RBCs coated with IgG3 A MoAb. Epitopes of A binding to IgG3 anti‐A A005 MoAb and BG‐2 MoAb differed in A‐zyme sensitivity. TNFα production in group B or O whole blood in response to the addition of A1 cells varied, but it essentially was abolished when group A cells were treated with 0.1 to 1.0 U of A‐zyme per mL of packed cells. A epitopes mediating immune hemolysis and hemagglutination with D. biflorus lectin were also cleaved by <5 U of A‐zyme per mL of packed cells. In contrast, hemagglutination with polyclonal anti‐A typing serum was diminished by only 1 to 2 serial titer dilutions.CONCLUSION: A epitopes mediating immune hemolysis and immune adherence to and activation of monocytic cells are highly sensitive to A‐zyme cleavage, as compared to those mediating hemagglutination with monoclonal and polyclonal anti‐A.
Anemia‐induced increase in the bleeding time:implications for treatment of nonsurgical blood loss
Authors: Valeri C. Robert , Cassidy George , Pivacek Linda E. , Ragno Gina , Lieberthal Wilfred , Crowley James P. , Khuri Shukri F. , Loscalzo Joseph 
Published: March 2003

BACKGROUND: Preoperative bleeding time (BT) does not correlate with postoperative bleeding in patients subjected to surgical procedures. A significant positive correlation has been reported between the BT 2 hours after cardiopulmonary bypass surgery and the nonsurgical blood loss during the first 4 hours after bypass surgery. This study was done to investigate the effect of Hct and platelet count on the BT measurement in normal, healthy men and women.STUDY DESIGN AND METHODS: To assess the relative effect of RBCs and platelets on the BT, 22 healthy male and 7 healthy female volunteers were subjected to the removal of 2 units of RBCs (360 mL), followed by the return of the platelet‐rich plasma (PRP) from both units and the infusion of 1000 mL of 0.9‐percent NaCl. Four of the men and all seven women received their RBCs 1 hour after their removal. Shed blood levels of thromboxane B2 (TXB2), 6‐keto prostaglandin F1α, and peripheral venous Hct were measured. BTs were measured in 15 men and 13 women before and after a plateletpheresis procedure to collect 3.6 × 1011 platelets per unit.RESULTS: The 2‐unit RBC apheresis procedure produced a 60‐percent increase in the BT associated with a 15‐percent reduction in the peripheral venous Hct and a 9‐percent reduction in the platelet count. The plateletpheresis procedure produced a 32‐percent decrease in the platelet count, no change in peripheral venous Hct, and no change in the BT. After the removal of 2 units of RBCs, the shed blood TXB2 level decreased significantly. Reinfusion of 2 units of RBCs restored the BT and restored the TXB2 level to the baseline levels.CONCLUSION: The acute reduction in Hct produced a reversible platelet dysfunction manifested by an increase in BT and a decrease in the shed blood TXB2 level at the template BT site. Return of the RBCs restored both the BT and the shed blood TXB2 level to normal. The platelet dysfunction observed with the reduction in Hct was due in part to a reduction in shed blood TXB2 and other, unknown mechanisms.
Platelet transfusion refractoriness associated withHPA‐1a (PlA1) alloantibody without coexistent HLA antibodies successfully treated with antigen‐negative platelet transfusions
Authors: Pappalardo Philip A. , Secord Ann R. , Quitevis Philippe , Haimowitz Marcia D. , Goldfinger Dennis 
Published: March 2003

BACKGROUND: Alloimmune‐mediated refractoriness to platelet transfusion is most commonly due to antibody to HLA antigens in multiply transfused or multiparous patients. Published reports of poor transfusion response due to antibodies to platelet‐specific antigens are rare and often confounded by the presence of coexistent antibodies against HLA antigens.CASE REPORT: A case is presented of a multiparous woman with acute myelogenous leukemia whose sole cause of transfusion refractoriness was antibody to platelet antigen HPA‐1a. She responded dramatically to HPA‐1a‐negative platelet transfusion.CONCLUSION: This case provides strong serologic and clinical evidence that platelet transfusion refractoriness may result from antibodies to platelet‐specific antigens.
Prospective RBC phenotype matching in a stroke‐prevention trial in sickle cell anemia: a multicenter transfusion trial
Authors: Vichinsky Elliott P. , Luban Naomi L.C. , Wright Elizabeth , Olivieri Nancy , Driscoll Catherine , Pegelow Charles H. , Adams Robert J. ,   for the Stroke Prevention Trial in Sickle Cell Anemia
Published: March 2003

BACKGROUND: Most sickle cell anemia patients undergo transfusion therapy to prevent complications. The Stroke Prevention Trial in Sickle Cell Anemia showed that transfusion therapy is effective in the primary prevention of stroke. Despite its efficacy, transfusion therapy is limited by alloimmunization. The purpose of this study was to determine if a multicenter trial could implement a transfusion program utilizing phenotypically matched blood to reduce alloimmunization.STUDY DESIGN AND METHODS: One hundred thirty children underwent RBC phenotyping and antibody screening with review of blood bank records. The protocol required use of WBC‐reduced RBCs, which were matched for E, C, and Kell. Monthly alloantibody testing and review of transfusion forms were performed to determine compliance and the occurrence of any adverse events.RESULTS: Patient RBCs expressed a low frequency of Kell (2%), E (20%), and C (25%) antigens. Sixty‐one patients received 1830 units. Ninety‐seven percent of all units were WBC reduced. Only 29 units were inadvertently not matched for E, C, and Kell. Five patients (8%) developed a clinically significant alloantibody. Four developed a single antibody to E or Kell. Three patients (5%) developed a warm autoantibody. There were 11 transfusion reactions and 8 transfusion‐associated events. Transfusion reactions included 6 febrile reactions (0.33%/unit), 3 allergic (0.16%/unit), and 2 hemolytic (0.11%/unit). Associated events included 4 episodes of hypertension (0.22%/unit), 3 crises (0.16%/unit), and 1 transient ischemic attack (0.05%/unit).CONCLUSION: This is the first multicenter study to show that extended RBC phenotyping can be implemented nationwide. Compared to studies, the alloimmunization rate dropped from 3 percent to 0.5 percent per unit, and hemolytic transfusion reactions dropped by 90 percent. It is recommended that all transfused sickle cell anemia patients be antigen matched for E, C, and Kell. Patients should be closely monitored during transfusions to avoid preventable risks.
DNA analysis for the Dombrock polymorphism
Authors: Rios Maria , Hue‐Roye Kim , Lee Agnes H. , Chiofolo Joseph T. , Miller Jeffrey L. , Reid Marion E. 
Published: March 2003

BACKGROUND: RBC typing for Doa and Dob is notoriously difficult, and inaccurate typing can predispose patients to hemolytic transfusion reactions. The DO1/DO2 polymorphism is associated with three nucleotide changes: 378 C>T, 624 T>C and 793 A>G. While the 378 C>T‐ and 624 T>C‐containing codons are silent mutations, the 793 A>G polymorphism in codon 265 encodes asparagine for Doa and aspartic acid for Dob.STUDY DESIGN AND METHODS: Described here are two PCR‐RFLP assays, one using the Mnl I site associated with 624C (DO2) and the other altering two nucleotides within the sense primer, which allows recognition of 793G by the Eam 1105 I.RESULTS: The assays have been performed on over 100 samples for which the RBC typing of one or both antigens was known. Eight samples had been historically mistyped by hemagglutination.CONCLUSION: This RFLP assay provides a practical method for typing donor blood for Dombrock alleles.
Screening for WBC antibodies by lymphocyte indirect immunofluorescence flow cytometry: superior to cytotoxicity and ELISA?
Authors: Lubenko Anatole , Rodi Katherine M. , Johnson Andrew C. 
Published: March 2003

BACKGROUND: Cytotoxic WBC antibodies are found in patients who have refractoriness to platelet transfusion (RPT) or are experiencing febrile transfusion reactions (FTRs) and in sera giving so called nonspecific hemagglutination by IAT (N/S IAT). Sera from such patients were screened for WBC antibodies regardless of the ability to fix complement using a flow cytometric (FC) lymphocyte indirect immunofluorescence test (LIFT) to compare FC‐LIFT with a routine lymphocytotoxicity test (LCT) for WBC antibody detection.STUDY DESIGN AND METHODS: Serum from 104 patients with RPT, 87 with FTR, and 147 with N/S IAT were tested in parallel by using FC‐LIFT and LCT. Sera giving discrepant results were re‐tested with an HLA class I antibody ELISA to assess whether they were HLA‐specific.RESULTS: Of the sera tested, 175 were LIFT positive, and 146 were LCT positive. Fifty‐five had antibodies that were detectable only by LIFT; 26 were positive only by LCT. Of these 81 discrepant sera, 30 of 63 were positive in HLA ELISA.CONCLUSION: FC‐LIFT detects more WBC antibodies than does LCT or ELISA, and it is a superior screening technique. Because some cytotoxic antibodies are detectable only by LCT, comprehensive WBC antibody screening would require the application of both techniques. However, because FC assessments of cytotoxicity have been described, LCTs may become redundant for WBC antibody screening.
K, Fya, and Jka phenotyping of donor RBCs on microplates
Authors: Diedrich Beatrice , Andersson Jan , Sallander Suzanne , Shanwell Agneta 
Published: March 2003

BACKGROUND: In many cases, the search for compatible blood for patients with clinically significant RBC alloantibodies is difficult and time‐consuming. To date, it has been considered necessary only to phenotype the blood donors for ABO group and D. There has been long experience with automated routine analysis (ABO, C, c, D, E, and e typing and RBC antibody screening), using robotic dispensers and computerized interpretation of microplate results. The purpose of this study was to explore the possibilities of also phenotyping for K, Fya, and Jka, as antibodies directed against these antigens (together with Rh antigens) are the most common clinically significant alloantibodies in the Swedish population.STUDY DESIGN AND METHODS: One thousand thirty‐one EDTA samples from blood donors were phenotyped for K, Fya, and Jka by use of an IAT with PEG on microplates. The findings were compared to those using conventional IAT in tube's and the microcolumn gel test (DiaMed‐ID, DiaMed).RESULTS: All typing results with the microplate method were correct. All reactions for K and Fya typing could be interpreted by the computer. The results for Jka were indeterminate in 1.4 percent (14/1031) of the samples.CONCLUSION: The PEG‐IAT microplate method gave reliable results that were suitable for routine phenotyping, thus making available a stock of phenotyped blood at reasonable cost, ready for delivery when required.
Effects of different concentrations of anticoagulant on the in vitro characteristics of autologous whole blood
Authors: Cober Nancy , Lacasse Margaret , Bart Bevan , Rock Gail 
Published: March 2003

BACKGROUND: Routinely, 450 mL of blood is collected into 63 mL of CPDA‐1, for a final anticoagulant:blood ratio of approximately 1:7 in a whole‐blood autologous unit. If less than 300 mL of blood is to be collected, the AABB standards suggest that there should be a proportionate decrease in anticoagulant. Data from an autologous blood program showed a range in volume from 92 mL to 667 mL per bag, which reflects an anticoagulant:blood ratio of 2:1 to 1:10.STUDY DESIGN AND METHODS: To determine the effects of these ratios on the in vitro function of RBCs at various anticoagulant ratios, blood was collected into different amounts of anticoagulant, and various measurements were made during storage.RESULTS: The number of RBCs and the MCV remained constant over time, regardless of the anticoagulant dilution used. Plasma free Hb increased with time with all dilutions. At a 1:2 ratio, it rose from 734 mg per L on Day 1 to 1805 mg per L on Day 35, and at 1:8, it was 355 mg per L for Day 1 and 854 mg per L on Day 35. Plasma sodium decreased and the potassium increased over time with all dilutions. From Day 1 to Day 35, there was a nine‐fold increase in potassium at both the 1:2 and 1:8 dilutions (2.4 to 22.9 mmol/L, 3.2 to 29.6 mmol/L, respectively). The LDH increased over time and the pH decreased in all of the dilutions. Osmotic fragility remained constant at the 1:8 dilution but decreased at all of the other dilutions with storage, with 44‐percent fragility on Day 35 at the 1:2 ratio. The WBC and platelet counts decreased consistently over time. Overall, 1 percent of the autologous units were below the cutoff volume of 300 mL at which an adjustment of the anticoagulant volume is required.CONCLUSION: Plasma Hb and plasma potassium concentrations are considerably higher in low‐volume units, which indicates that deviation from standard collection procedures is deleterious to RBCs.