RESUMEN
BACKGROUND AND OBJECTIVES: In Canada, plasma sent for fractionation is tested for both parvovirus B19 (B19V) and hepatitis A virus (HAV). This study compared positivity rates of B19 and HAV nucleic acid tests (NATs) in Canadian plasma samples for the pre-COVID-19 restriction era (2015 to end of February 2020 [Q1] 2020) and the post-COVID-19 restriction era. MATERIALS AND METHODS: Pooled EDTA plasma specimens were tested within 24 months of blood draw using the Procleix Panther System (Grifols Diagnostic Solutions Inc, San Diego, CA, USA) for B19V and HAV detection. Reactive pools were resolved by individual specimen testing. RESULTS: Between 1 January 2015, and 31 March 2022, 3,928,619 specimens from Canadian plasma donors were tested for B19V. For the same period, 3,922,954 specimens were tested for HAV. To account for a lag in specimen testing for up to 24 months, the data were divided into: (1) a pre-pandemic period (1 January 2015-31 March 2020; B19V tested n = 2,412,701, B19V NAT-positive n = 240 [0.01%], HAV tested n = 2,407,036, HAV NAT-positive n = 26 [0.001%]); (2) a two-year mixed-impact period (1 April 2020-31 March 2022; B19V tested n = 968,250, B19V NAT-positive n = 14 [0.001%], HAV tested n = 968,250, HAV NAT-positive n = 2 [0.0002%]); and (3) a pandemic-impact period (1 April 2022-31 March, 2023; B19V tested n = 597,668, B19V NAT-positive n = 3 [0.0005%], HAV tested n = 597,668, HAV NAT-positive n = 1 [0.0002%]). CONCLUSION: The percentage of B19V- and HAV-positive donations was significantly reduced from the pre-pandemic period to the pandemic-impact period.
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Donantes de Sangre , COVID-19 , Parvovirus B19 Humano , Humanos , COVID-19/sangre , COVID-19/epidemiología , Canadá/epidemiología , Hepatitis A/sangre , Hepatitis A/epidemiología , SARS-CoV-2 , Masculino , Femenino , Virus de la Hepatitis A , Infecciones por Parvoviridae/sangre , Infecciones por Parvoviridae/epidemiologíaRESUMEN
BACKGROUND: Tn syndrome is an acquired form of polyagglutination arising from somatic mutations of hematopoietic stem cells. Tn red blood cells (RBCs) are agglutinable by naturally occurring anti-Tn antibodies in most adult sera. Current ABO typing reagents are monoclonal and do not detect polyagglutination on forward typing. However, herein we describe a case of Tn activation that was suspected due to cross-reactivity with a monoclonal anti-A reagent. STUDY DESIGN AND METHODS: A 63-year-old man with myeloproliferative neoplasm, who historically typed as group O, demonstrated unexpected mixed field reactivity with anti-A reagent using a gel-based method. However, manual tube testing was consistent with the patient's historical group O type. RESULTS: Lectin testing demonstrated reactivity with Salvia sclarea and Glycine soja, but not Arachis hypogea. The patient's RBCs produced positive crossmatches with healthy donor sera, but reactivity was eliminated by ficin pretreatment of the RBCs. Ficin treatment also resolved typing discrepancies on gel-based typing. No reactivity was noted using cord blood sera, and N antigen expression was diminished upon phenotyping. Tn activation was confirmed by detection of a novel 4-nucleotide deletion (c.395-398del) in exon 3 of C1GALT1C1 resulting in a truncated glycosyltransferase. CONCLUSION: This case of acquired Tn polyagglutination due to a novel mutation was first suspected from an ABO phenotyping discrepancy. It highlights the cross-reactivity of anti-A reagent with Tn antigen when tested on a common gel-based method. Furthermore, the case demonstrates that review of patient history and test information can clarify discrepancies and guide resolution.
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Sistema del Grupo Sanguíneo ABO , Ficaína , Adulto , Antígenos de Carbohidratos Asociados a Tumores , Tipificación y Pruebas Cruzadas Sanguíneas , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVES: Blood group genotyping has been used in different populations. This study aims at evaluating the genotypes of common blood group antigens in the Omani blood donors and to assess the concordance rate with obtained phenotypes. MATERIAL AND METHODS: Blood samples from 180 Omani donors were evaluated. Samples were typed by serological methods for the five blood group systems MNS, RH (RHD/RHCE), KEL, FY and JK. Samples were genotyped using RBC-FluoGene vERYfy eXtend kit (inno-train©). Predicted phenotypic variants for 70 red blood cell antigens among the MNS, RH (RHD/RHCE), KEL, FY, JK, DO, LU, YT, DI, VEL, CO and KN blood group systems were assessed. RESULTS: Simultaneous phenotype and genotype results were available in 130 subjects. Concordance rate was >95% in all blood group systems with exception of Fy(b+) (87%). Homozygous GATA-1 mutation leading to erythroid silencing FY*02N.01 (resulting in the Fy(b-)ES phenotype) was detected in 81/112 (72%) of genotyped samples. In addition, discrepant Fyb phenotype/genotype result was obtained in 14/112 samples; 13 of which has a heterozygous GATA-1 mutation and one sample with a wild GATA genotype. D and partial e c.733C>G variants expressing the V+VS+ phenotype were found in 22/121 (18.2%) and 14/120 (11.7%) of the samples, respectively. Di(a-b+), Js(a-b+), Yt(a+b-) and Kn(a+b-) genotype frequencies were 99.4%, 95.8%, 91.9% and 97.7%, respectively. CONCLUSION: In conclusion, we report a high frequency of FY*02N.01 allele due to homozygous c.-67T>C GATA-1 single-nucleotide variation. This is the first study reporting the detailed distribution of common and rare red cell genotypes in Omani blood donors.
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Antígenos de Grupos Sanguíneos , Alelos , Donantes de Sangre , Antígenos de Grupos Sanguíneos/genética , Genotipo , Humanos , FenotipoRESUMEN
BACKGROUND AND OBJECTIVES: Under the ISBT, the Working Party (WP) for Red Cell Immunogenetics and Blood Group Terminology is charged with ratifying blood group systems, antigens and alleles. This report presents the outcomes from four WP business meetings, one located in Basel in 2019 and three held as virtual meetings during the COVID-19 pandemic in 2020 and 2021. MATERIALS AND METHODS: As in previous meetings, matters pertaining to blood group antigen nomenclature were discussed. New blood group systems and antigens were approved and named according to the serologic, genetic, biochemical and cell biological evidence presented. RESULTS: Seven new blood group systems, KANNO (defined numerically as ISBT 037), SID (038), CTL2 (039), PEL (040), MAM (041), EMM (042) and ABCC1 (043) were ratified. Two (039 and 043) were de novo discoveries, and the remainder comprised reported antigens where the causal genes were previously unknown. A further 15 blood group antigens were added to the existing blood group systems: MNS (002), RH (004), LU (005), DI (010), SC (013), GE (020), KN (022), JMH (026) and RHAG (030). CONCLUSION: The ISBT now recognizes 378 antigens, of which 345 are clustered within 43 blood group systems while 33 still have an unknown genetic basis. The ongoing discovery of new blood group systems and antigens underscores the diverse and complex biology of the red cell membrane. The WP continues to update the blood group antigen tables and the allele nomenclature tables. These can be found on the ISBT website (http://www.isbtweb.org/working-parties/red-cell-immunogenetics-and-blood-group-terminology/).
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Antígenos de Grupos Sanguíneos , COVID-19 , Eritrocitos , Humanos , Antígenos de Grupos Sanguíneos/genética , Transfusión Sanguínea , Inmunogenética , Pandemias , Eritrocitos/inmunologíaRESUMEN
Despite the recent advancements in transfusion medicine, red blood cell (RBC) alloimmunization remains a challenge for multiparous women and chronically transfused patients. At times, diagnostic laboratories depend on difficult-to-procure rare reagent RBCs for the identification of different alloantibodies in such subjects. We have addressed this issue by developing erythroblasts with custom phenotypes (Rh null, GPB null and Kx null/Kell low) using CRISPR/Cas9 gene-editing of a human induced pluripotent stem cell (hiPSC) parent line (OT1-1) for the blood group system genes: RHAG, GYPB and XK. Guide RNAs were cloned into Cas9-puromycin expression vector and transfected into OT1-1. Genotyping was performed to select puromycin-resistant hiPSC KOs. CRISPR/Cas9 gene-editing resulted in the successful generation of three KO lines, RHAG KO, GYPB KO and XK KO. The OT1-1 cell line, as well as the three KO hiPSC lines, were differentiated into CD34+ CD41+ CD235ab+ hematopoietic progenitor cells (HPCs) and subsequently to erythroblasts. Native OT1-1 erythroblasts were positive for the expression of Rh, MNS, Kell and H blood group systems. Differentiation of RHAG KO, GYPB KO and XK KO resulted in the formation of Rh null, GPB null and Kx null/Kell low erythroblasts, respectively. OT1-1 as well as the three KO erythroblasts remained positive for RBC markers-CD71 and BAND3. Erythroblasts were mostly at the polychromatic/ orthochromatic stage of differentiation. Up to ~400-fold increase in erythroblasts derived from HPCs was observed. The availability of custom erythroblasts generated from CRISPR/Cas9 gene-edited hiPSC should be a useful addition to the tools currently used for the detection of clinically important red cell alloantibodies.
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Sistemas CRISPR-Cas , Diferenciación Celular , Linaje de la Célula , Eritroblastos/metabolismo , Edición Génica , Células Madre Pluripotentes Inducidas/metabolismo , Biomarcadores , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/metabolismo , Línea Celular , Eritroblastos/citología , Técnicas de Silenciamiento del Gen , Hematopoyesis , Histocitoquímica , Humanos , Inmunofenotipificación , Células Madre Pluripotentes Inducidas/citología , ARN Guía de Kinetoplastida/genéticaRESUMEN
BACKGROUND: The Scianna (SC) blood group system comprises seven antigens. They reside on the erythroblast membrane-associated glycoprotein (ERMAP). The ERMAP and RHCE genes are juxtaposed to each other on chromosome 1. We report a novel SC antigen. STUDY DESIGN AND METHODS: Blood samples came from a patient and his two sisters in Saudi Arabia. To investigate the antibody specificity we used the column agglutination technique and soluble recombinant ERMAP protein. The significance of anti-SCAR was evaluated by the transfusion history and a monocyte monolayer assay. We determined the genomic sequence of ERMAP and RHCE genes. RESULTS: The patient's serum showed an antibody of titer 8 against a high-prevalence antigen. The soluble recombinant ERMAP protein inhibited the antibody. The propositus genotyped homozygous for an ERMAP:c.424C>G variant, for which his sisters were heterozygous. The c.424C>G variant occurred in the SC*01 allele in one haplotype with the RHCE*03 (RHCE*cE) allele. No signs of hemolysis occurred following an incompatible blood transfusion. The monocyte monolayer assay was negative. CONCLUSIONS: We characterized a high-prevalence antigen, with the proposed name "SCAR," which is the eighth antigen of the Scianna blood group system (proposed designation 013.008). Individuals homozygous for ERMAP:p.(Gln142Glu) protein variant can produce anti-SCAR. Although we did not observe any sign of hemolysis at this time, the anti-SCAR prompted a change of the treatment regimen. A review of the known reports indicated that all SC alloantibodies of sufficient titer should be considered capable of causing hemolysis.
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Anemia de Células Falciformes/terapia , Antígenos de Grupos Sanguíneos/genética , Butirofilinas/genética , Reacción a la Transfusión/sangre , Alelos , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/genética , Antidrepanocíticos/uso terapéutico , Antígenos de Grupos Sanguíneos/inmunología , Transfusión Sanguínea/métodos , Butirofilinas/inmunología , Femenino , Genotipo , Haplotipos , Heterocigoto , Homocigoto , Humanos , Hidroxiurea/uso terapéutico , Isoanticuerpos/genética , Masculino , Monocitos/metabolismo , Polimorfismo de Nucleótido Simple , Prevalencia , Sistema del Grupo Sanguíneo Rh-Hr/genética , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Arabia Saudita/epidemiología , Reacción a la Transfusión/genética , Adulto Joven , Talasemia beta/complicacionesRESUMEN
BACKGROUND: The continual identification of rare blood among donors is critical to support national programs like the American Rare Donor Program (ARDP). Some blood centres require consent from donors to be registered with a national registry. This situation provides an opportunity to determine whether a donor's willingness to register is associated with a change in donation behaviour. METHODS: Rare donors were identified by molecular typing. The average number of donations per year was compared for each donor prior to and after receiving a consent letter. Donors were categorized as either accepting or declining the request. Non-parametric t tests compared the statistical significance within and between categories. Rare types were overlaid with consensus data to look for trends using data visualization techniques. RESULTS: A total of 270 molecularly typed rare donors received letters over 4 years. Half of the donors (132, 49%) agreed to participate in the ARDP. Overall, donation frequency increased after the letter when enrolled. Both Caucasian and non-Caucasian donors increased their donations after enrolling providing an additional 159 red blood cell units over 3 years. Declining participation did not change donation frequency. Data visualization showed that enrolled donors were more affluent, high school and college educated, and lived in their home for longer periods of time. CONCLUSION: A donor's willingness to enrol in the ARDP was associated with a post-response increase in donation frequency. New interventions to reach non-Caucasian donors may be a prerequisite to increase donation frequency and a willingness to be a rare blood donor.
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Donantes de Sangre/educación , Seguridad de la Sangre/métodos , Visualización de Datos , Técnicas de Genotipaje/métodos , Adulto , Donantes de Sangre/psicología , Seguridad de la Sangre/psicología , Humanos , Consentimiento Informado , Educación del Paciente como Asunto/métodosRESUMEN
BACKGROUND: Typically minor ABO incompatible platelet products are transfused without any incident, yet serious hemolytic transfusion reactions occur. To mitigate these events, ABO 'low titer' products are used for minor ABO incompatible transfusions. We sought to understand the role of IgM/IgG and complement activation by anti-A on extravascular hemolysis. METHODS: Samples evaluated included (i) Group O plasma from a blood donor whose apheresis platelet product resulted in an extravascular transfusion reaction, (ii) Group O plasma from 12 healthy donors with matching titers that activated complement (N = 6) or not (N = 6), and (iii) Group O sera from 10 patients with anti-A hemolysin activity. A flow cytometric monocyte erythrophagocytosis assay was developed using monocytes isolated by immunomagnetic CD14-positive selection from ACD whole blood of healthy donors. Monocytes were frozen at - 80 °C in 10% dimethyl sulfoxide/FBS and then thawed/reconstituted on the day of use. Monocytes were co-incubated with anti-A-sensitized fluorescently-labeled Group A1 + RBCs with and without fresh Group A serum as a source of complement C3, and erythrophagocytosis was analyzed by flow cytometry. The dependency of IgM/IgG anti-A and complement C3 activation for RBC erythrophagocytosis was studied. Anti-A IgG subclass specificities were examined for specific samples. RESULTS: The plasma and sera had variable direct agglutinating (IgM) and indirect (IgG) titers. None of 12 selected samples showed monocyte-dependent erythrophagocytosis with or without complement activation. The donor sample causing a hemolytic transfusion reaction and 2 of the 10 patient sera with hemolysin activity showed significant erythrophagocytosis (> 10%) only when complement C3 was activated. The single donor plasma and two sera demonstrating significant erythrophagocytosis had high IgM (≥ 128) and IgG titers (> 1024). The donor plasma anti-A was IgG1, while the patient sera were an IgG3 and an IgG1 plus IgG2. CONCLUSION: High anti-A IgM/IgG titers act synergistically to cause significant monocyte erythrophagocytosis by activating complement C3, thus engaging both Fcγ- and CR1-receptors.
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Incompatibilidad de Grupos Sanguíneos , Reacción a la Transfusión , Sistema del Grupo Sanguíneo ABO , Humanos , Inmunoglobulina G , Inmunoglobulina MRESUMEN
BACKGROUND: The provision of units with antigen-negative attributes is required for alloimmunized transfusion recipients and to avoid alloimmunization among patients on chronic transfusion support. Recent evidence confirms that the demand for antigen-typed units is increasing. STUDY DESIGN AND METHODS: A cloud-based search engine was designed by the blood center to find antigen-negative units. The service provided access to historical antigen information for units in hospital inventories. The hospital transfusion service was required to confirm the antigen phenotype. The results of 16 hospitals' use over 5 years were analyzed to determine trends and value of the service. The time commitment of the cloud-based query was compared to the hospital performing manual phenotyping with an outcome of at least one unit found with the desired antigen-negative attribute(s). RESULTS: Hospitals were located between 4 miles and 200 miles away from the blood center. A total of 6,081 queries were submitted over the 5 years, with an overall 50% success rate of finding at least one unit. Single antigen queries accounted for 67% of total searches, with two antigen queries and three or more antigen queries accounting for 24% and 9% of the units found, respectively. The cloud-based antigen query was most efficient for combined antigen frequencies <0.5 for two or more antigen-negative attributes. CONCLUSION: A cloud-based search engine provides hospitals with access to historical antigen information housed at the blood center. Future refinements may consider regulatory submission of a process to provide confirmed historical information through this cloud-based program.
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Nube Computacional , Bases de Datos Factuales , Inventarios de Hospitales/métodos , Motor de Búsqueda/métodos , Donantes de Tejidos/estadística & datos numéricos , HumanosRESUMEN
BACKGROUND: The clinical and laboratory features of hemolytic disease of the newborn can be challenging to diagnose during pregnancy in the apparent absence of a blood group antibody. Low-frequency antibodies go undetected due to the lack of appropriate antigen-positive reagent red blood cells (RBCs). CASE REPORT: A pregnant woman of Southeast Asian descent was referred to a maternal-fetal medicine outpatient clinic due to a complicated obstetric history and a negative antibody screen. This initial visit at 29 weeks and 0 days' gestational age (GA) was unremarkable. A hydropic infant, born at 29 weeks and 5 days' GA, succumbed on the seventh day of life. Comprehensive laboratory testing was performed after birth. The hospital blood bank performed a maternal antibody identification. Direct antiglobulin test was performed on the cord blood. A reference laboratory confirmed an anti-Mia , performed paternal Mia phenotyping, and identified a hybrid glycophorin B-A-B GP*Mur allele. DISCUSSION: Maternal alloimmunization to low-frequency antigens remains a challenge. Southeast Asians make up a significant percentage in some US locations. Worldwide reports on the frequency of maternal alloimmunization of the MNS system can be used to guide the use of specific reagent RBCs for testing. Such strategies rely on the identification of blood donor units for reagent manufacture and use in perinatal antibody screens. CONCLUSION: The incidence of Mia and related antibodies is significant among Southeast Asians. In North America, prenatal antibody screening cells are not routinely chosen to match this population. The clinical and societal implications are discussed.
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Eritroblastosis Fetal/etiología , Isoanticuerpos/inmunología , Sistema del Grupo Sanguíneo MNSs/inmunología , Adulto , Asiático , Prueba de Coombs , Eritroblastosis Fetal/inmunología , Femenino , Feto/inmunología , Glicoforinas/inmunología , Humanos , Masculino , América del Norte , EmbarazoRESUMEN
BACKGROUND: Human immunoglobulin G (hIgG) includes four different subtypes (IgG1, IgG2, IgG3, and IgG4). Due to genetic variations, each IgG subtype contains different isoallotypes. It was previously shown that a Food and Drug Administration-approved monoclonal anti-IgG failed to recognize 2 of 15 recombinant, human IgG3 anti-Kell (K1) isoallotypes (rIgG3-03 and rIgG3-13) by indirect antiglobulin test (IAT). STUDY DESIGN AND METHODS: We expressed and purified 15 recombinant human rIgG3 anti-K1 isoallotypes and investigated their antigen binding and ability to induce phagocytosis using homozygous (KK) and heterozygous (Kk) K1-positive red blood cells (RBCs) by gel IAT, flow cytometry, and a monocyte monolayer assay (MMA) with peripheral blood monocytes and cultured inflammatory (M1) and anti-inflammatory (M2) macrophages. RESULTS: MMA results showed that differences in the Fc region of rIgG3 anti-K1 led to distinctive phagocytic activity with both monocytes and M1 macrophages. rIgG3-18 and rIgG3-19 showed an enhanced ability to induce phagocytosis. Differences in Fc regions also led to variations in the number of antibodies bound to KK RBCs. Despite the differences in phagocytic activity, all 15 rIgG3 clones are predicted to induce clinically significant hemolysis if K1-positive blood was transfused into patients. CONCLUSION: These results argue that antiglobulin reagents that fail to detect isoallotype rIgG3-03 or rIgG3-13 could present a transfusion risk or lack of detection of a potentially clinically significant anti-K1 in hemolytic disease of the fetus and newborn.
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Inmunoglobulina G/inmunología , Pruebas Inmunológicas/normas , Sistema del Grupo Sanguíneo de Kell/inmunología , Fagocitosis/inmunología , Antígenos/inmunología , Antígenos/metabolismo , Eritrocitos/inmunología , Hemólisis/inmunología , Humanos , Alotipos de Inmunoglobulinas/inmunología , Isoanticuerpos/inmunologíaRESUMEN
Maternal alloantibody-mediated hemolytic disease of the fetus and newborn (HDFN) ranges from no or mild symptoms to severe hydrops and intrauterine fetal demise. Hemolytic anti-D-mediated HDFN proceeds via a long-known mechanism, to which three other pathways to fetal/neonatal anemia may be added: (0) Fetal erythrocyte destruction can proceed by extravascular phagocytosis. (1) An apoptotic pathway has been described for anti-Kell, and anti-Ge3. (2) Erythropoietic suppression may arise from altered or deformed erythroblast architecture in anti-M-mediated disease. (3) Clonal escape from erythropoietic suppression is hypothesized to arise from maternal anti-Jra immune pressure, albeit this requires further elucidation. Alloantibody-mediated anemic disease of the fetus and newborn (ADFN) is a designation we favor for cases when hemolysis or hyperbilirubinemia are not the dominant features, such as those provoked by anti-Kell, anti-Ge3, anti-M, and anti-Jra.
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Anemia/genética , Eritroblastosis Fetal/inmunología , Hemólisis/inmunología , Sistema del Grupo Sanguíneo de Kell/inmunología , Anemia/fisiopatología , Femenino , Feto , Humanos , Recién NacidoRESUMEN
The U antigen (MNS5) is one of 49 antigens belonging to the MNS blood group system (ISBT002) carried on glycophorins A (GPA) and B (GPB). U is present on the red blood cells in almost all Europeans and Asians but absent in approximately 1.0% of Black Africans. U negativity coincides with negativity for S (MNS3) and s (MNS4) on GPB, thus be called S-s-U-, and is thought to arise from homozygous deletion of GYPB. Little is known about the molecular background of these deletions. Bioinformatic analysis of the 1000 Genomes Project data revealed several candidate regions with apparent deletions in GYPB. Highly specific Gap-PCRs, only resulting in positive amplification from DNAs with deletions present, allowed for the exact genetic localization of 3 different breakpoints; 110.24- and 103.26-kb deletions were proven to be the most frequent in Black Americans and Africans. Among 157 CEPH DNAs, deletions in 6 out of 8 African ethnicities were present. Allele frequencies of the deletions within African ethnicities varied greatly and reached a cumulative 23.3% among the Mbuti Pygmy people from the Congo. Similar observations were made for U+var alleles, known to cause strongly reduced GPB expression. The 110- and 103-kb deletional GYPB haplotypes were found to represent the most prevalent hereditary factors causative of the MNS blood group phenotype S-s-U-. Respective GYPB deletions are now accessible by molecular detection of homo- and hemizygous transmission.
RESUMEN
Donor red cell genotyping provides efficiencies to identify "in demand" blood donors for transfusion recipients requiring antigen-negative blood. Donor red cell genotype information can be used to label units with historical types and introduced throughout the supply chain from the blood center to the hospital transfusion service and has potential to be used in recruitment strategies.
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Donantes de Sangre , Visualización de Datos , Selección de Donante/métodos , Eritrocitos/metabolismo , Ensayos Analíticos de Alto Rendimiento/métodos , Etiquetado de Productos , Antígenos de Grupos Sanguíneos/análisis , Antígenos de Grupos Sanguíneos/metabolismo , Tipificación y Pruebas Cruzadas Sanguíneas/métodos , Tipificación y Pruebas Cruzadas Sanguíneas/normas , Transfusión Sanguínea/métodos , Transfusión Sanguínea/normas , Selección de Donante/normas , Eritrocitos/química , Genotipo , Técnicas de Genotipaje/métodos , Ensayos Analíticos de Alto Rendimiento/normas , Humanos , Tamizaje Masivo/métodos , Tamizaje Masivo/normas , Polimorfismo de Nucleótido Simple , Etiquetado de Productos/métodos , Etiquetado de Productos/normasRESUMEN
BACKGROUND: Heavy workload in hospital transfusion services and blood centers necessitates the implementation of automated platforms. We evaluated the performance of Erytra Eflexis (Diagnostic Grifols), a recently developed midsize automated instrument for pretransfusion testing, in comparison with a US Food and Drug Administration (FDA)-cleared device (Erytra). Reproducibility and repeatability of the results were also investigated. STUDY DESIGN AND METHODS: Studies were conducted using the same card technology and reagents at three US sites. Tests were performed on 9174 specimens from hospital patients (55.61%) and blood donors (43.39%). Evaluations included 18,413 ABO/D/reverse typing; 9084 Rh phenotypes, 4640 K phenotypes, 2052 antibody screenings, 1232 antibody identifications, 469 direct antiglobulin tests, 612 IgG crossmatches, and 700 ABO-compatibility crossmatches. A reference blood panel was also sent to each center, for a total of 3900 replicate tests. Concordance between results with the two instruments and performance among the different centers were statistically evaluated. RESULTS: Agreement between instruments was 99.84% for 37,202 test results, with 61 discrepancies (0.16%). Percentages of positive and negative agreement were 99.82% and 99.85%, respectively. No discrepancies were observed in 12,276 tests for direct ABO/D grouping. Discrepancies were observed during antibody identification (n = 19), antibody screening (n = 15), and reverse grouping (n = 10). Investigations of the discrepancies were resolved in favor of the study instrument in 55.73% of the cases. Erytra Eflexis obtained the expected results in the reproducibility analysis. CONCLUSION: This multicenter study demonstrates that Erytra Eflexis with its gel card technology and reagents is reliable and substantially equivalent to the FDA-cleared instrument used as the reference.
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Tipificación y Pruebas Cruzadas Sanguíneas/instrumentación , Seguridad de la Sangre/instrumentación , Transfusión Sanguínea , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Tipificación y Pruebas Cruzadas Sanguíneas/métodos , Seguridad de la Sangre/métodos , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: The overall number of red blood cell (RBC) units distributed to hospitals throughout the world and in the United States has decreased lately. This study was performed to determine if the number of antigen-negative RBC units distributed to hospitals has followed this trend. STUDY DESIGN AND METHODS: Stratified by ethnicity, data on total RBC distributions and antigen-negative RBC distributions from six large blood collectors in the United States were obtained from 2009 through 2016. An antigen-negative unit was defined as a unit with a specific RBC phenotype that had been specially ordered as such by a hospital. RESULTS: Overall, 10,103,703 RBC units were distributed by these six blood collectors; 650,516 (6.4%) were distributed as antigen-negative units. While the overall number of RBCs distributed decreased by 27.2% between 2009 and 2016, the number of antigen-negative RBC distributions increased by 39.5%. In each year, the majority of the distributed antigen-negative RBCs were donated by whites. However, antigen-negative RBC units from black or African American donors were distributed in a disproportionately high fraction compared to the overall number of RBCs distributed from these donors. Most of the one through four antigen-negative RBCs were donated by whites. However, as antigen matching became more extensive, the proportion of units distributed from black or African American donors increased such that they were the predominant donors of five or more antigen-negative units. CONCLUSION: Blood collectors will need to be aware of the trend of increasing antigen-negative distributions despite decreased overall distributions.
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Antígenos de Grupos Sanguíneos/análisis , Transfusión de Eritrocitos/estadística & datos numéricos , Etnicidad/estadística & datos numéricos , Grupos Raciales/estadística & datos numéricos , Bancos de Sangre/estadística & datos numéricos , Bancos de Sangre/tendencias , Donantes de Sangre/estadística & datos numéricos , Incompatibilidad de Grupos Sanguíneos/prevención & control , Tipificación y Pruebas Cruzadas Sanguíneas , Transfusión de Eritrocitos/tendencias , Femenino , Humanos , Masculino , Prescripciones , Estados UnidosRESUMEN
Gerbich (Ge) antigens are high frequency red cell antigens expressed on glycophorin C (GYPC) and glycophorin D. Hemolytic disease of the fetus and newborn (HDFN) due to Gerbich antibody is rare and presents a clinical challenge, as Gerbich negative blood is scarce. We report a case of HDFN due to maternal Ge3 negative phenotype and anti-Ge3 alloimmunization, successfully managed by transfusion of maternal blood. Molecular testing revealed that the mother has homozygous deletion of exon 3 of GYPC, the father is homozygous wildtype for GYPC, and the infant is obligate heterozygote expressing Ge3.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Biomarcadores/análisis , Prestación Integrada de Atención de Salud , Enfermedades Hematológicas/terapia , Hemólisis , Adulto , Terapia Combinada , Femenino , Enfermedades Hematológicas/inmunología , Enfermedades Hematológicas/metabolismo , Humanos , Recién Nacido , MasculinoRESUMEN
The GYPC gene encodes the glycophorins C and D. The two moieties express 12 known antigens of the Gerbich blood group system and functionally stabilize red blood cell membranes through their intracellular interaction with protein 4.1 and p55. Three GYPC exon deletions are responsible for the lack of the high-frequency antigens Ge2 (Yus type, exon 2 deletion), Ge2 and Ge3 (Gerbich type, exon 3 deletion), and Ge2 to 4 (Leach type, exons 3 and 4 deletion), but lack exact molecular description. A total of 29 rare blood samples with Yus (GE:-2,3,4) and Gerbich (GE:-2,-3,4) phenotypes, including individuals of Middle-Eastern, North-African or Balkan ancestry were examined genetically. All phenotypes could be explained by 4 different Yus alleles, characterized by deletions of exon 2 and adjacent introns, and 3 different Gerbich alleles, with deletions of exon 3 and adjacent introns. A 3600 base pair GYPC region, encompassing exon 2 and flanking region, shares a high degree of sequence homology with a region flanking exon 3, probably representing an evolutionary duplication event. Defining the expression of Gerbich variants presently relies on rare serological reagents. Our approach substitutes the serological characterization with a precise genotype approach to identify the rare Yus and Gerbich alleles.
Asunto(s)
Antígenos de Grupos Sanguíneos/genética , Incompatibilidad de Grupos Sanguíneos/genética , Puntos de Rotura del Cromosoma , Eliminación de Gen , Glicoforinas/genética , Alelos , Antígenos de Grupos Sanguíneos/inmunología , Incompatibilidad de Grupos Sanguíneos/inmunología , Transfusión Sanguínea , Niño , Exones/genética , Femenino , Antecedentes Genéticos , Humanos , Isoanticuerpos/genética , Masculino , Fenotipo , Reacción en Cadena de la Polimerasa/métodosRESUMEN
Anti-CD38 is used to treat relapsed or treatment-refractory multiple myeloma. CD38 monoclonal antibodies, however, can interfere with routine blood bank serologic tests. Agglutination is observed at the indirect phase of testing as the drug binds to red blood cells (RBCs). Resolving the testing interference causes delays issuing RBC units to patients with anemia. A number of devised methods to eliminate or bypass the effects of anti-CD38 on serologic tests are in use but no panacea exists. The limitations of each method require each testing site tailor an approach to best fit their needs. We present perspectives and testing practices from a hospital transfusion medicine service and an Immunohematology Reference Laboratory managing pretransfusion samples with anti-CD38.
Asunto(s)
ADP-Ribosil Ciclasa 1/inmunología , Anticuerpos Monoclonales/inmunología , Eritrocitos/metabolismo , Humanos , Pruebas Serológicas/métodos , Medicina Transfusional/métodosRESUMEN
BACKGROUND: Anti-CD38 therapy causes interference with both the direct and the indirect antiglobulin tests. We describe the experience from an Immunohematology Reference Laboratory and model cost options for providing safe transfusions. STUDY DESIGN AND METHODS: Phenotyping, genotyping, and antibody identification orders were retrospectively reviewed in the setting of anti-CD38 therapy. The data were used to model the added cost of transfusion support. Four approaches were evaluated: 1) thiol-treated reagent red blood cells (RRCs) in antibody investigations with K- red blood cell (RBC) transfusions, 2) patient phenotyping or 3) genotyping with antigen-matched RBC transfusions, and 4) a combination of interval thiol-treated RRC antibody investigations with genotype antigen-matched RBC transfusions. RESULTS: Sixty-two patients were identified as receiving anti-CD38 therapy. Thiol-treated RRC antibody investigations (28/62 patients) were favored over genotyping (23/62) and combination testing (11/62). Patient phenotyping failed to detect useful antigen information on eight patients: seven Fyb silencing mutations and one partial e. A thiol-treated RRC antibody investigation was the least expensive testing method for the first transfusion, but four- and five-antigen-matched RBC transfusions were equal in cost within five and 21 transfusion events, respectively. CONCLUSION: Genotyping provided a more accurate antigen status than phenotyping patient RBCs. Patients requiring long-term transfusion support benefit from antigen matching when matching less than four antigens. Ultimately, the decision to genotype or use thiol-treated RRC antibody investigations will vary for each hospital blood bank.