bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatal graft‐versus‐host disease associated with transfusions of HLA‐ matched, HLA‐homozygous platelets from unrelated donors
Authors: Benson K. , Marks A.R. , Marshall M.J. , Goldstein J.D. 
Published: March 2003

BACKGROUND: Transfusion‐associated graft‐versus‐host disease (TA‐GVHD) due to blood from HLA‐homozygous related and unrelated blood donors has been described. CASE REPORT: Fatal TA‐GVHD due to the transfusion of HLA‐matched platelets from an unrelated HLA‐homozygous donor is reported. A 61‐year‐old man with a history of diabetes mellitus and myelodysplastic syndrome was diagnosed with acute myelogenous leukemia in November 1991. Induction chemotherapy resulted in aplasia, which was followed by a normocellular marrow with mild dysplasia and continued karyotypic abnormalities. High‐dose chemotherapy was given in a second attempt to achieve complete remission. HLA‐matched platelets were ordered when platelet refractoriness developed. The patient was HLA‐ heterozygous for HLA‐A and ‐B antigens (A2, 29; B37, 44). Over the next 7 days, four unirradiated HLA‐matched plateletpheresis units were transfused; one was probably homozygous for both HLA‐A and ‐B antigens (A2, ‐; B44, ‐) and was transfused first, and three were probably homozygous for an HLA‐B antigen (A2, 29; B44, ‐) and were white cell reduced. No blood relatives served as donors. Seven days after the first HLA‐matched platelet transfusion, fever, chills, and diarrhea developed; 2 days later, a rash was present. Liver enzymes increased markedly. Renal and respiratory failure ensured. A skin biopsy was consistent with GVHD. Despite immunosuppressive therapy, the patient died 19 days after the first HLA‐matched platelet transfusion.CONCLUSION: TA‐GVHD has been recognized in immunocompromised, HLA‐ heterozygous patients receiving blood from blood relatives who are HLA‐ homozygous. patients receiving blood from either blood relatives or non‐ blood relatives who are HLA‐homozygous. This HLA‐heterozygous patient received transfusions of unirradiated, class I HLA‐homozygous platelets, which were specifically ordered as HLA‐matched, and his death was attributed to TA‐GVHD. Consideration should always be given to providing irradiated blood for immunosuppressed patients, especially when HLA‐matched platelets are used, to prevent TA‐GVHD.
A “new” low‐incidence red cell antigen, LOCR, associated with altered expression of Rh antigens
Authors: Coghlan G. , McCreary J. , Underwood V. , Zelinski T. 
Published: March 2003

Background: Mild cases of hemolytic disease of the newborn were being studied when it was recognized that the propositi's red cells carried a novel antigen.Study Design and Methods: Serologic and genetic studies of a new low‐incidence antigen, LOCR (International Society of Blood Transfusion series number 700.53), were performed.Results: The antigen is associated with altered expression of the Rh antigen c in two unrelated families and in a third proposita and with an altered expression of e in a fourth proposita. The lods for the gene controlling LOCR relative to Rh are 2.107 at θ = 0.00; that is, they fall short of the requirement for inclusion of the antigen in the Rh blood group system. LOCR is excluded from the ABO, MNS, Lutheran, Kell, Duffy, Kidd, Xg, Chido/Rodgers, Kx, and Gerbich blood group systems. Genetic evidence suggests it is not part of the Yt, Colton, or LW systems.Conclusion: Serologic evidence that LOCR is associated with altered expression of c or e strongly suggests that LOCR is part of the Rh blood group system. However, the genetic evidence falls short of the level required for system assignment.
Effect on cardiovascular function and iron metabolism of the acute removal of 2 units of red cells
Authors: Sherman L.A. , Lippmann M.B. , Ahmed P. , Buchholz D.H. 
Published: March 2003

BACKGROUND: The collection from a donor of 2 red cell units at one time would decrease recipient exposure to viruses and alloantigens. If the donor is a large person, the blood volume lost and the postdonation hemoglobin and/or hematocrit should be within acceptable limits. If the donor is a large person, the blood volume lost and the postdonation hemoglobin and/or hematocrit should be within acceptable limits. The effect on cardiovascular function and iron metabolism requires description.STUDY DESIGN AND METHODS: Manual 2‐unit erythropheresis was performed on eight donors, with the plasma returned. Donors had treadmill testing of maximum aerobic power (VO2max) before donation, 24 hours after, and 8 to 11 weeks after. Serial samples were drawn for iron metabolism studies.RESULTS: Donors weighed 61.2 to 74.8 kg, and 9.6 to 11.4 percent of their blood volume was removed. Mean VO2max decreased from 84 percent of that predicted before donation to 74 percent 24 hours afterward. By 8 to 11 weeks, hemoglobin returned to acceptable donor levels and mean VO2max was 92 percent of that predicted. Mean hemoglobin fell from 14.4 to 11.7 g per dL (144 to 117 g/L) and rose to 13.9 g per dL (139 g/L) at 16 weeks. At 16 weeks, serum iron (120 ± 47 vs. 83 ± 33 micrograms/dL [21 ± 8 vs. 15 ± 6 mumol/L]), ferritin (40 ± 24 vs. 18 ± 10 ng/mL [40 ± 20 vs. 20 ± 10 micrograms/L]), and free erythroprotoporphyrin (19 ± 5 vs. 28 ± 5 micrograms/dL [0.34 ± 0.09 vs. 0.50 ± 0.09 mumol/L]) differed significantly from baseline levels. No major donor symptoms occurred.CONCLUSION: Two‐unit erythropheresis was done with blood volume loss and postdonation hemoglobin no worse than those that would occur in a 50‐kg donor donating 450 mL. Cardiovascular effects and donor symptoms were mild. Two‐unit red cell donations would be clinically advantageous, and they warrant further studies of both utility and donor safety.
Alloimmune neonatal neutropenia resulting from immunization to a high‐ frequency antigen on the granulocyte Fc gamma receptor III
Authors: Bux J. , Hartmann C. , Mueller‐Eckhardt C. 
Published: March 2003

BACKGROUND: Alloimmune neonatal neutropenia is mainly caused by NA‐ or NB1‐specific alloantibodies. An antibody in the serum of a Turkish mother who had given birth to an infant with alloimmune neonatal neutropenia showed no NA or NB specificity and was therefore investigated further.STUDY DESIGN AND METHODS: The number of antibody‐ binding sites was calculated by determination of elutable IgG from granulocytes using a quantitative sandwich enzyme‐linked immunosorbent assay. Complement activation was tested by immunofluorescence (C3d) and cytotoxicity tests. The antigen was identified using the antigen‐ capture assay, monoclonal antibody‐specific immobilization of granulocyte antigens, and a modified immunoprecipitation method based upon biotinylation of proteins and visualization by luminescence (luminoimmunoprecipitation). Family study and determination of antigen frequency were done by immunofluorescence and agglutination tests.RESULTS: A noncytotoxic, granulocyte‐specific alloantibody that recognized the Fc gamma receptor III, independent of the NA phenotype, was detected, and 242,000 binding sites per cell were calculated. Of granulocytes from 150 randomly selected German blood donors, the alloantibody bound to all. The maternal cells were typed NA1/NA2‐ and NB1‐positive.CONCLUSION: These data reveal the presence of a previously unrecognized, high‐frequency epitope on the granulocyte Fc gamma receptor III. Luminoimmunoprecipitation proved to be a simple, nonradioactive technique that was useful in identifying the molecule involved.
Direct oral questions to blood donors: the impact on screening for human immunodeficiency virus
Authors: JOHNSON E.S. , DOLL L.S. , SATTEN G.A. , LENES B. , SHAFER A.W. , KAMEL H. , CASANOVA R.J. , PETERSEN L.R. 
Published: March 2003

BACKGROUND: In December 1990, the Food and Drug Administration recommended that all United States blood centers implement a policy of asking prospective donors direct oral questions (DOQs) about human immunodeficiency virus (HIV) risk behaviors to increase the safety of the blood supply.STUDY DESIGN AND METHODS: To evaluate the impact of the DOQ policy, HIV‐related deferral and HIV seroprevalence data were analyzed at four American Red Cross blood centers for the year before the policy change and the year after. An epidemiologic analysis with stratification was conducted, including the calculation of odds ratios (OR) and 95‐percent CIs.RESULTS: Two of the four blood centers showed an overall significant increase in HIV‐related deferral after implementation of the DOQ policy: OR = 4.04, (95% CI = 3.41, 4.76); OR = 2.93, (95% CI = 2.67, 3.21). The increase in HIV‐related deferral was higher for women. HIV seroprevalence decreased at all four centers, including the two that did not see an increase in HIV‐related deferrals. Seroprevalence declined by 14 percent in the two centers with increases in HIV‐related deferral, which was neither significant nor attributable to DOQs.CONCLUSION: Given that HIV antibody screening cannot detect HIV‐seronegative (but infectious) “window‐period” donations, the deferral of at‐risk donors may offer some additional protection to the blood supply. However, evidence was not found of an increase in safety of the blood supply as measured by HIV seroprevalence.
Multiple‐unit and second transfusions of red cells enzymatically converted from group B to group O: report on the end of phase 1 trials
Authors: Lenny L.L. , Hurst R. , Zhu A. , Goldstein J. , Galbraith R.A. 
Published: March 2003

BACKGROUND: It has previously been shown that 1 and 2 units (200 – 400 mL) of red cells (RBCs) enzymatically converted from group B to group O by treatment with alpha‐galactosidase (ECO RBCs) are safe and efficacious when transfused to normal group O or A persons.STUDY DESIGN AND METHODS: The current report describes studies in which 1) normal group A and O subjects received large volumes of these cells (3 units), 2) some group O subjects underwent transfusion several months later, and 3) ECO RBCs were prepared by the use of recombinant coffee bean alpha‐galactosidase and transfused to a group O subject, to demonstrate the in vivo equivalence of ECO RBCs, whether prepared with native or recombinant alpha‐galactosidase.RESULTS: Clinical evaluation (hematologic tests, chemistry analysis, urinalysis) and serologic analyses did not reveal any evidence of subtle or acute transfusion reaction or significant increase in preexisting anti‐B titer. ECO RBC survival within the circulation of the recipients was normal (24‐hour survival, 95.5 +/− 0.9%; t1/2, 34.7 +/− 6.1 days; n = 8 transfusions), and the efficacy of the transfusions was manifested in elevations in recipient hemoglobin and hematocrit (hemoglobin increase, 1.5 +/− 0.6 g/dL; hematocrit increase, 3.6 +/− 1.6%; n = 8 transfusions).CONCLUSION: ECO RBCs are safe and efficacious when transfused more than once or in multiple‐unit volumes to group O or A subjects, and ECO RBCs prepared with recombinant or native enzyme are equivalent in vivo.
Mammalian genotoxicity assessment of methylene blue in plasma: implications for virus inactivation
Authors: Wagner S. J. , Cifone M. A. , Murli H. , Dodd R. Y. , Myhr B. 
Published: March 2003

BACKGROUND: The risk of adverse consequences of virus‐inactivation procedures for plasma and cellular blood components must be less than the risk of transfusion‐associated viral disease. Previous studies demonstrated that methylene blue, which is currently used in Europe for virus inactivation in fresh‐frozen plasma, can elicit mutations in bacterial test systems. This study investigates the potential for methylene blue genotoxicity in two mammalian test systems.STUDY DESIGN AND METHODS: Different concentrations of methylene blue were prepared in plasma (heat‐treated at 56 degrees C for 1 hour to reduce cytotoxicity) and used, without illumination, in an in vitro mouse lymphoma cell assay designed to detect forward mutations in the gene encoding thymidine kinase. The assay was performed in the presence or absence of rat liver S9 microsomal fraction. Similarly prepared samples of methylene blue in heat‐treated plasma were used in an in vivo mouse micronucleus assay. Each system included a negative vehicle control (heat‐treated plasma without methylene blue) and a positive control consisting of a known genotoxic agent.RESULTS: Intravenous administration to mice of 62 mg per kg of methylene blue did not increase the frequency of micronuclei in polychromatic red cells harvested from bone marrow. However, methylene blue concentrations of 10 micrograms per mL (with S9 activation) and 30 micrograms per mL (without S9 activation) significantly increased the thymidine kinase mutation frequency of mouse lymphoma cells to approximately 110 × 10(‐ 6), from a spontaneous frequency of 28 × 10(‐6).CONCLUSION: Methylene blue is mutagenic in cultured mammalian cells. In contrast, results from the mouse micronucleus assay suggest that the genotoxicity is not expressed in vivo. Considerably more investigation will be required to assess the genotoxic potential of intravenously administered methylene blue used in virus‐inactivation procedures, because of the likelihood of the formation of methylene blue photoproducts or the impact of metabolic conversion of methylene blue to leukomethylene blue in vivo.
Protection of human polymorphonuclear leukocyte function from the deleterious effects of isolation, irradiation, and storage by interferon‐γ and granulocyte‐colony‐stimulating factor
Authors: Rex J. H. , Bhalla S. C. , Cohen D. M. , Hester J. P. , Vartivarian S. E. , Anaissie E. J. 
Published: March 2003

BACKGROUND: Fungal infections represent a difficult challenge to clinicians caring for neutropenic patients with hematologic malignancies, as antifungal therapy often has limited success in that setting. One promising yet problematic alternative approach is leukocyte transfusion. The isolation of polymorphonuclear leukocytes (PMNs) induces apoptosis and functional deterioration, and irradiation to prevent transfusion‐associated graft‐versus‐host disease causes further functional deterioration.STUDY DESIGN AND METHODS: The ability of interferon‐gamma and granulocyte‐colony‐stimulating factor (G‐CSF), used both alone and in combination, to protect PMNs after 0 or 20 hours' storage in cell culture (as a model for function after transfusion) and irradiation with 0, 5, or 30 Gy was studied.RESULTS: Without cytokine treatment, 20‐hour‐old PMNs showed marked apoptosis, no appreciable chemotaxis, and no ability to kill Candida albicans. In contrast, cytokine treatment significantly reduced apoptosis and protected chemotaxis, C. albicans killing, and surface‐receptor expression from both storage and irradiation. Although the majority of the benefit appeared to be due to G‐CSF, consistent trends suggested better function of PMNs after combined treatment with interferon‐gamma and G‐CSF.CONCLUSION: Judicious use of cytokines may preserve PMN function. These findings have important implications for the transfusion of PMNs to cytopenic patients.
Anti‐A and/or anti‐B is not detectable in some patients who underwent ABO‐incompatible bone marrow transplantation
Authors: Maeda K. , Taniwaki K. , Santo T. , Itsukuma T. , Ito M. , Anan K. , Misawa M. , Ohe Y. , Kai S. , Hara H. 
Published: March 2003

BACKGROUND: Recently, anti‐A and/or anti‐B produced by B cells from donor marrow could not be detected for more than 20 weeks in some patients who had undergone ABO‐incompatible bone marrow transplantation (BMT).STUDY DESIGN AND METHODS: Twelve to 72 weeks after 11 patients underwent ABO‐incompatible BMT, titers of anti‐A and anti‐B were assayed, A and B antigens were identified by routine methods and flow cytometry, direct and indirect antiglobulin tests were performed, and the red cell antibody was eluted.RESULTS: In some patients who underwent ABO‐incompatible BMT, anti‐A and/or anti‐B produced by the B cells from the donor marrow could not be detected after BMT when red cells taken from the patients before BMT carried the corresponding antigen‐that is, when hematopoiesis had already changed the cells to the donor's type according to ABO blood typing. Furthermore, some blood samples from those patients gave positive results in direct antiglobulin tests. Blood typing of patients after BMT showed mixed‐ field agglutination. In one patient, the half‐life of red cells assayed with 51Cr was 22.4 days (30.0 +/− 4.0 days for normal controls).CONCLUSION: Although many hypotheses could be considered to explain the present data, the possibility is proposed that anti‐A and/or anti‐B in the sera must have been consumed in some patients who underwent ABO‐ incompatible BMT. This may lead to problems such as difficulty of ABO typing, positive direct antiglobulin tests, and a relatively short life span of red cells.
Patterns of care for and outcomes of Pneumocystis carinii pneumonia among persons with transfusion‐acquired AIDS
Authors: Bennett C.L. , Horner R.D. , Aboulafia D. , Weinstein R.A. 
Published: March 2003

BACKGROUND: The most common human immunodeficiency virus (HIV)‐related cause of death in persons with transfusion‐acquired (TA) AIDS has been Pneumocystis carinii pneumonia (PCP). While better treatment for PCP accounts for improved survival among HIV‐infected homosexual or bisexual men, the extent to which others have benefitted from these developments is unknown.STUDY DESIGN AND METHODS: Patterns of PCP care among persons with TA‐AIDS, intravenous drug users, and homosexual or bisexual men are compared.RESULTS: TA‐AIDS patients were older (mean, 46 years vs. < 40 for others, p < 0.05), more severely ill (59% had an alveolar‐arterial oxygen gradient > 48.5 torr vs. 41% of others, p < 0.05), and less likely to have received PCP prophylaxis (16% of TA‐AIDS patients versus 24–41% of others, p < 0.05). PCP care and outcomes also differed: TA‐AIDS patients were less than half as likely to have early use of PCP medications (relative odds ratio = 0.45; 95% CI, 70% vs. > 80% for others, p < 0.05), more likely to be intubated (22% vs. 9–13% of others, p < 0.05), and more likely to die in‐hospital (26% vs. 13‐ 22% of others, p < 0.05). After controlling for differences in severity of illness, insurance, age, and hospital characteristics, TA‐AIDS patients were 45 percent as likely to have early PCP therapy (95% CI, 22%, 91%) as were persons in high‐risk groups.CONCLUSION: For persons whose only risk factor was transfusion, recognition of the HIV infection and its complications appears to be problematic, which may help explain poorer outcomes in persons with HIV‐related PCP.
A Bombay individual lacking H and Le antigens but expressing normal levels of α‐2‐ and α‐4‐fucosyltransferases
Authors: Shechter Y. , Etzioni A. , Levene C. , Greenwell P. 
Published: March 2003

BACKGROUND: The rare Bombay phenotype is usually due to a primary genetic defect in an alpha‐2‐ or alpha‐4‐fucosyltransferase. The present study was done to investigate a patient with normal transferases, who exhibits the Bombay phenotype. CASE REPORT: Red cells of the patient, his parents, and siblings were phenotyped for A, B, and H antigens. The presence of B, H, and Le transferases in serum and saliva was measured.RESULTS: The parents and siblings were all group B, Le(a‐b‐). The propositus was typed as Oh, Le(a‐b‐). His serum contained anti‐A, anti‐B, and anti‐H. Normal levels of B, H, and Le transferases were found in all family members including the patient.CONCLUSION: In an unusual case, a person has the Bombay phenotype, but normal levels of transferases in serum and saliva. A general defect in fucose metabolism seems to be the primary abnormality in this case.
Flow cytometric detection of platelet‐reactive antibodies and application in platelet crossmatching
Authors: Kohler M. , Dittmann J. , Legler T.J. , Lynen R. , Humpe A. , Riggert J. , Neumeyer H. , Pies A. , Panzer S. , Mayr W.R. 
Published: March 2003

Background: Alloimmunization against HLA or platelet antigens can cause refractoriness to platelet transfusions in multiply transfused patients. Crossmatching of platelet concentrates is effective in overcoming this problem.Study Design and Methods: A flow cytometric assay was used for simultaneous detection of lymphocyte‐reactive and platelet‐reactive antibodies in a single sample using fluorescein isothiocyanate‐labeled anti‐IgG. This assay was compared with the monoclonal antibody‐specific immobilization of platelet antigens (MAIPA) assay in selected sera containing HLA and platelet antibodies. In a further study, this assay was compared with lymphocytotoxicity test results from thrombocytopenic patients, for whom platelet concentrates were ordered. The results of both assays were then correlated with the 1‐hour corrected count increment, with a corrected count increment greater then 7500 considered as an adequate transfusion response.Results: The results of the MAIPA and flow cytometric assay in detecting platelet‐reactive antibodies correlated well (p<0.0001, r = 0.84). The sensitivity and specificity of the flow cytometric assay in detecting platelet‐reactive antibodies were 94.7 and 96.3 percent, when the MAIPA assay was taken as a reference. In unselected sera from patients, the sensitivity and specificity of the flow cytometric assays were, respectively, 72.7 and 91.7 percent in detecting lymphocyte‐ reactive antibodies and 70.6 and 77.7 percent in detecting platelet‐ reactive antibodies, when the lymphocytotoxicity test was used as a reference. With regard to an adequate transfusion response, the sensitivities and efficiencies were 20.0 and 82.1 percent, 33.3 and 84.3 percent, and 70.0 and 88.6 percent for the lymphocytotoxicity test and the lymphocyte‐reactive and platelet‐reactive flow cytometric assays, respectively.Conclusion: Flow cytometric crossmatching appears to be an effective method of detecting platelet‐reactive antibodies that may affect the success of platelet transfusions. This procedure is well‐suited for routine conditions and can be performed within 2 hours.
Genotyping of the human platelet antigen systems 1 through 5 by multiplex polymerase chain reaction and ligation‐based typing
Authors: Legler T. J. , Kohler M. , Mayr W.R. , Panzer S. , Ohto H. , Fischer G. F. 
Published: March 2003

BACKGROUND: Platelet‐specific antibodies may be involved in refractoriness to platelet transfusions, disorders such as neonatal alloimmune thrombocytopenia, and post‐transfusion purpura. Genotyping for the major human platelet antigen (HPA) systems HPA‐1 through HPA‐5 is of considerable help in establishing the diagnoses of these diseases.STUDY DESIGN AND METHODS: A new genotyping method is described. Alleles of all five systems are amplified in a multiplex polymerase chain reaction. Subsequently, aliquots of the amplification products are thermocycled in the presence of a pair of allele‐specific oligonucleotide probes and a heat‐stable ligase. After heat denaturation, the probes hybridize adjacent to complementary sequences of the amplification product. In a perfect match, the two probes become covalently joined. Detection of the ligation product is performed with an enzyme‐linked immunosorbent assay.RESULTS: Complete concordance of genotypes between the ligation‐based typing and established genotyping methods was determined in 54 Austrian (HPA‐1, −2, −3, and −5) and 56 Japanese (HPA‐4) individuals. Ligation‐based genotyping of HPA‐1 polymorphism using platelet‐derived RNA as starting material gave concordant results in all 15 cases tested.CONCLUSION: Multiplex polymerase chain reaction in combination with ligation‐based typing allows fast typing of large numbers of platelet donors and screening for critical antigens in pregnant women.