Statistical Analysis of Monocyte Monolayer Assay Validation in Brazilian Blood Donors

Aims: To validate the monocyte monolayer assay (MMA) technique concerning its suitability for blood donor screening and its cost per test performed. The MMA is an in vitro simulation of the behavior of the antibodies, demonstrating the reactions that would occur in the endothelial reticulum system after a transfusion of incompatible red blood cells, indicating the risk of a hemolytic transfusion reaction and therefore of the clinical significance of the antibodies. Study Design: Blood samples of alloimmunized patients, selected at random from a blood donation bank, were submitted to validation tests recommended by the Brazilian National Health Surveillance Agency for the approval of new testing procedures. Place and Duration of Study: The following Brazilian institutions were involved between June 2009 and July 2010: Immunohematology laboratory of the Hematology and Hemotherapy Center of Santa Catarina state in Florianópolis, Department of Medicine (Medical Unit IV) and Department of Radiology of the Institute of Medical Sciences, Hospital Lahore in São Paulo. Methodology: Ninety samples of alloimmunized patients treated by the Santa Catarina blood donors were used. The validation tests evaluated the selectivity, linearity, precision, and accuracy of the MMA method and determined the limits of detection and quantification. External validation of the method was performed by comparing these results with those of an independent laboratory in São Paulo, while making sure that the latter was blind to the results of the former. The coefficient of variation was used to express the MMA testing precision of 5 replicates across 5 different concentration levels. Type I error for evaluating statistical significance was set at 5%. Results: Selectivity assessment of the impact of multiple alloantibodies on the MMA test result showed no statistically significant difference (P>0.05) across the titers of 64, 256, and 2048, each with three replications, thus confirming the test specificity. Homoscedasticity of the monocyte index (MI) data was not refuted by Levine's test with the F-value of 0.746, much below the value of 3.056 needed to achieve a statistical significance level of P<0.05. MI linearity against the logarithm of the alloantibody concentration was shown in a simple linear regression where the latter predicted 83% of the variation in the former, and the regression slope of 0.4 (95% confidence interval 0.32, 0.48). The limits of detection and quantification on the logarithm scale were 0.28 and 0.84, respectively. External validation found no statistically significant difference between the MMA test results from the two independent laboratories. The coefficient of variation of <15% indicated good MMA testing precision under routine laboratory conditions. Conclusion: The assay met all validation criteria and was therefore effective in assessing the clinical significance of alloantibodies.

Analysis of red blood cell alloimmunization among inpatients: 104 588 cases / 中国输血杂志

【Objective】 To analyze the yield, specificity and detection time of red blood cell(RBC)alloimmunization in 104 588 inpatients. 【Methods】 The clinical information of patients who underwent at least one antibody screening in our hospital from November 2017 to December 2019 was retrospectively analyzed. The demographic characteristics, transfusion history, pregnancy history and antibody screening results of patients were collected. The RBC alloantibody yield, specificity and detection time were analyzed, and differences of transfusion units and frequency between patients with and without alloimmunization were compared. 【Results】 Eight hundred cases of alloantibodies with clinical significance were detected in blood samples of 723 patients, with a positive rate of 0.7% (723/104 588). The incidence rate of alloimmunization in females was higher than that in males (0.9% vs 0.5%, P<0.05). Rh alloantibodies accounted for 76.4%(611/800), of which 61.4%(375/611)were anti-E. Transfusion units and frequency of patients with alloimmunity were higher than those without(median: 6.0 vs 4.0, P<0.05; 4.0 vs 2.0, P<0.05, respectively). And 67.5% of RBC alloantibodies were detected within 6 months, with the median (IQR) detection time of 97.0 (22.5-247.0) days. 【Conclusion】 Routine antibody screening should be performed before transfusion in order to reduce the occurrence of adverse reactions, and Rh typing transfusion with compatible crossmatch should be performed if necessary.

Frequency of antigen Dia on the blood donor population of the Hemocenter coordinator of the Hemopa Foundation

ABSTRACT Introduction: Erythrocyte phenotyping is a very important test in the adoption of prophylactic measures to reduce transfusion reactions/alloimmunizations in polytransfused patients. The blood group Diego, in its current, form has 22 antigens, of which 4 are immunogenic, being Dia/Dib and Wra/Wrb, while the others are less expressive. The antigen Dia is of low incidence among whites and blacks, however, it is common in the South American indigenous and Asian Mongolian populations. It is also considered a system of clinical importance for its immunogenicity. Method: The present study aimed to carry out a retrospective and descriptive survey of the frequency of the Dia antigen in the blood donor population at the HEMOPA Foundation Coordinating Blood Center from 12/2018 to 1/2000. The data obtained were from the HEMOPA Foundation SBS Progress and SBS WEB Systems databases. Results: During this period, 941,744 blood bags were collected and, of these, 930 bags were phenotyped for the Dia antigen, of which 842 were negative and 88 (9.7%) positive. The research showed that, among the positive donors for the antigen Dia, 88.6% were brown, 3.4%, black and 8%, white. In the statistical analysis, the frequency observed was higher in browns. Conclusion: In the present investigation, we concluded that our region has a relatively higher frequency of the Dia antigen, when compared to the rest of Brazil, and it occurs more often in browns.

Anti-Chido/Rodgers antibodies in a patient with infectious disease / Anticuerpos anti-Chido/Rodgers en paciente con enfermedad infecciosa

Introduction: Red cell alloimmunization is an immune response against foreign red cell antigens, usually occurring due to sensibilization in blood transfusions and pregnancies. The Chido (Ch) and Rodgers (Rg) antigens are present in about 96-98 percent of the population in general. Patients who have antibodies against antigens of high frequency in the population are a problem for transfusion medicine. Objectives: To describe the case of a patient diagnosed with AIDS and invasive cancer of the rectum with a recent hospitalization for lower gastrointestinal bleeding and anemia with the presence of anti-Ch and anti-Rg and the difficulties and solutions found for handling the case. Case presentation: Anti-Ch and anti-Rg have not been found to cause a hemolytic transfusion reaction (HTR) or hemolytic disease of the fetus and newborn (HDFN). However, the clinical presentation and laboratory findings including the immunohematological workups concerning the reaction are discussed, with a special emphasis on the benefit of identifying such an antibody and providing a compatible blood unit for transfusion support of the patient. Conclusions: When an antibody against a high-frequency erythrocyte antigen is identified in African or American-descent, anti-Ch or anti-Rg should be considered and that transfusion tests should not be delayed due to its clinical importance(AU)

Introducción: La aloinmunización de glóbulos rojos es una respuesta inmune frente a antígenos de glóbulos rojos extraños, que pueden ocurrir por sensibilización en transfusiones de sangre y embarazos. Los antígenos Chido (Ch) y Rodgers (Rg) están presentes en aproximadamente el 96-98 por ciento de la mayoría de la población. Los pacientes que tienen anticuerpos contra antígenos de alta frecuencia poblacional son un problema para la medicina transfusional. Objetivos: Describir caso de un paciente diagnosticado de AIDS y cáncer invasivo de recto con hospitalización reciente por hemorragia digestiva baja y anemia con presencia de anti-Ch y anti-Rg y las dificultades y soluciones encontradas para el manejo del caso. Presentación de caso: No se ha encontrado que Anti-Ch y anti-Rg causen reacciones hemolíticas transfusionales y enfermedad hemolítica del recién nacido. Sin embargo, se discuten la presentación clínica y los hallazgos de laboratorio, incluidos los estudios inmunohematológicos con respecto a la reacción, con especial énfasis en el beneficio de identificar dicho anticuerpo y obtener una unidad de sangre para transfusión que respalde al paciente con respecto a proporcionar una unidad compatible. Conclusiones: Cuando se identifica anticuerpos contra un antígeno eritrocitario de alta frecuencia, en afrodescendientes o americanos, se deben considerar Anti-Ch o anti-Rg y no retrasar las pruebas de transfusión por su importancia clínica(AU)

Guía de manejo obstétrico y del recién nacido en madre aloinmunizada / Guidelines for the obstetric management of an alloimmune mother and her newborn / Guia de manejo obstétrico e neonatal em mães aloimunizadas

Resumen: La aloinmunización es una respuesta biológica frente a la exposición de antígenos no propios. La gestación, las transfusiones de hemocomponentes, los trasplantes de órganos sólidos y células hematopoyéticas, así como el consumo de drogas intravenosas exponen a las pacientes al desarrollo de aloanticuerpos antieritrocitarios. El hallazgo de los mismos debe cumplir con las instancias diagnósticas para identificar la probabilidad de estar asociados a enfermedad hemolítica feto neonatal (EHFN) y su oportuna derivación a policlínica de alto riesgo obstétrico (ARO) para su correcto seguimiento. Es fundamental que sean los laboratorios de inmunohematología de los servicios de hemoterapia y medicina transfusional los encargados de los estudios diagnósticos de aloinmunización eritrocitaria(1). En este sentido hemos elaborado esta guía con el objetivo de protocolizar de manera multidisciplinaria el manejo de las embarazadas aloinmunizadas y sus recién nacidos.

Abstract: Alloimmunization is the biological response to exposure to non-HLA antigens. Pregnancy, transfusion of blood components, solid organ and hematopoietic cell transplantation, as well as intravenous drug use expose patients to the development of anti-erythrocyte antibodies. When the latter are found, they must match diagnostic criteria to identify the potential association to hemolytic disease of the fetus and newborn (HDFN) and its timely referral to the high-risk obstetric risk polyclinic for due follow-up. It is of the essence for erythrocyte alloimmunization diagnostic tests to be carried out by the immunohematology laboratories of the Hemotherapy and Transfusional Medicine services. To that end, we have prepared these guidelines with the purpose of providing a multidisciplinary protocol for the handling of maternal alloimmunization and alloimmunization of the newborn.

Resumo: A aloimunização é uma resposta biológica à exposição a antígenos não próprios. A gravidez, as transfusões de hemocomponentes, os transplantes de órgãos sólidos e células hematopoiéticas, bem como o uso de drogas intravenosas expõem os pacientes ao desenvolvimento de anticorpos antieritrocitários. O achado destes deve obedecer a critérios diagnósticos para identificar a doença e a probabilidade de estarem associados a doença hemolítica feto neonatal (DHPN) e seu encaminhamento oportuno para uma unidade de alto risco obstétrico para acompanhamento adequado. É fundamental que os laboratórios de imuno-hematologia dos serviços de Hemoterapia e Medicina Transfusional se encarreguem dos estudos diagnósticos da aloimunização eritrocitária. Elaboramos este guia com o objetivo de estabelecer um protocolo multidisciplinar para o manejo de gestantes aloimunizadas e seus recém-nascidos.

Inmunización feto materna contra antígenos de HLA en mujeres de una población paraguaya / Fetomaternal immunization against HLA antigens in women from a Paraguayan population

El embarazo es la única causa natural de inmunización contra el sistema de Antígenos Leucocitarios Humano (HLA). Durante la gestación hay paso de leucocitos fetales a través de la placenta, lo que puede desencadenar en la madre una respuesta inmunológica contra los antígenos HLA fetales de origen paterno, con la consecuente producción de anticuerpos. El objetivo del estudio fue conocer la prevalencia de sensibilización a antígenos HLA inducida por embarazos en mujeres paraguayas y estudiar las características y especificidades de los anticuerpos encontrados. Realizamos un estudio descriptivo, prospectivo, de corte transversal de 319 mujeres paraguayas, que acudieron al Laboratorio Central de Salud Pública entre abril de 2017 y abril de 2018 utilizando la tecnología LUMINEX para la detección de anticuerpos anti- HLA. Se encontraron anticuerpos anti-HLA en 46% de las mujeres multíparas. Se detectaron anticuerpos contra todos los antígenos testados. La gran mayoría de los sueros resultaron ser poliespecíficos. Concluimos que al aumentar el número de gestas no solo aumenta la probabilidad de una mujer de desarrollar anticuerpos anti- HLA, sino que también parece aumentar la cantidad de especificidades desarrolladas y el título de los anticuerpos

Pregnancy is the only natural cause of immunization against the Human Leukocyte Antigen (HLA) system. During pregnancy, fetal leukocytes pass through the placenta, which can trigger an immunological response in the mother against the fetus paternal HLA antigens, with the consequent production of antibodies. The objective of this study was to determine the prevalence of pregnancy-induced HLA antigen sensitization in Paraguayan women and to study the characteristics and specificities of the antibodies found. We conducted a descriptive, prospective, cross-sectional study of 319 Paraguayan women, who attended the Central Laboratory of Public Health between April 2017 and April 2018 using LUMINEX technology to detect anti-HLA antibodies. We found anti-HLA antibodies in 46% of multiparous women. Antibodies against all tested antigens were detected. The vast majority of the sera exhibited multiple specificities. We conclude that increasing the number of gestations not only increases a woman's likelihood of developing anti-HLA antibodies, but it also appears to increase the number of developed specificities and titers of antibodies

Safety of RhD alloimmunization / 中国输血杂志

【Objective】 To explore the safety of RhD-positive red blood cells (RBCs) immunization schedules in RhD-negative volunteers, so as to facilitate the development of domestic anti-D immunoglobulin. 【Methods】 From January 2018 to April 2020, 23 RhD negative volunteers with informed consent were enrolled and divided into initial immunization group and booster immunization group. The initial immunization included first immunization, second immunization and third immunization. Four groups, i. e. 3 cases of 20 mL, 8 of 30 mL, 6 of 40 mL, and 6 of 50 mL, were involved in initial immunization. After the initial immunization response, booster immunizations were performed every 3 months. According to the anti-D titer before each immunization, the booster immunization doses were set to 0.5, 1 and 2 mL. Whole blood samples of 5mL/ person (time) were collected 24 h and 1 week after each infusion, and the blood routine, liver, kidney and blood coagulation function and anti-D titer were detected. The differences of detection (index) values at 24 h and 1 week after the first immunization and booster immunization in each (dose) group were compared. 【Results】 No statistically significant differences were observed in hemolysis index values (all within the range of medical reference values) 24 h or 1 week after initial immunization among RhD positive RBCs of 20, 30, 40 and 50mL(P>0.05). The differences between the hemolysis index values and the basic values before the immune response (all within the range of medical reference values) after 0.5 or 1 mL booster immunizations were also not statistically different (P>0.05). However, the differences (μmol/L)between total bilirubin levels and the basic values before the immune response (1.55±1.87, 6.29±2.66) were significantly different after 2 mL booster immunization (P<0.05). 【Conclusion】 No risks affecting the safety of RhD negative volunteers was found in the immunization schedule proposed in this study.

Detection of red cell alloantibodies in thalassaemia patients

Background: ?-thalassaemia patients receive regular blood transfusion to thrive. Due to antigen disparity between the blood donors and these patients they develop red cell alloantibodies due to alloimmunization.' The objective of this study is to predict the frequency of red cell alloimmunization amongst ?-thalassaemia major patients receiving regular blood transfusion.Methods: This study including 106 patients with ?-thalassaemia was conducted in the department of Transfusion Medicine, S. C. B. Medical College, Cuttack for a period of 12 months. Alloantibodies to different red cell blood group antigens in multi-transfused thalassaemia patients were detected using the glass bead technology for blood group serology in the present study.Results: Out of 106 ?-thalassaemia major patients included in the study, 7.5% of patients developed alloantibodies, all being clinically significant. The alloantibodies were anti-E, anti c, anti e and anti-D. The rate of incidence of these alloantibodies was 3.8%, 1.9%, 0.9% and 0.9% respectively.' There was a significant association between alloantibody formation with number of transfused packed red cells (Mann-Whitney Test: p value = 0.035) and age at first transfusion (p value = 0.001). The factors having no association with alloimmunization to red cell antigens are age and gender.Conclusions: Alloimmunization to various erythrocyte blood group antigens is a common problem in multi-transfused ?-thalassaemia patients. There is an association between number of transfused packed red cells and age at first transfusion with alloantibody formation in the study.

Prevalence of red blood cell alloimmunization in multiply transfused patients

Introduction: To analyze the prevalence of alloantibodies in multiply transfused patients. Methods: This study was a retrospective, exploratory and descriptive study with a quantitative approach. The study sample comprised 185 patients transfused at a referral service in the city of Passo Fundo, Rio Grande do Sul, from January 2016 to February 2018. Results: Overall, the antibodies identified were as follows: anti-E in 47 patients (18%), anti-D and anti-K in 28 patients each (11%), anti-C in 21 patients (8.1%), and inconclusive antibody results in 23 patients (8.9%). Females were a majority (55.7%), mean age was 48.8 years and mean quantity of blood transfused was 7.2 bags. Cardiovascular disorders were the most common comorbidities, in 39 patients (21.2%), followed by oncological disorders, in 38 patients (18.4%). Conclusion: Alloimmunization is an important and frequent clinical condition that increases the risk of hemolytic reactions and is associated with significant patient morbidity and mortality. (AU)

Procedencia y fenotipo del sistema Rh en donantes negativos en un Hemocentro colombiano / Origin and phenotype of the Rh system in negative donors in a Colombian hemocenter

percentIntroducción: El sistema Rh está compuesto por más de 56 antígenos capaces de producir enfermedad hemolítica, definidos por métodos serológicos. Los más importantes y, por ello denominados antígenos mayores del sistema, son los antígenos D, C, c, E y e. Estos antígenos se ubican sobre dos proteínas que se expresan en la membrana de los eritrocitos Rh D y RhCE. Objetivo: Determinar la frecuencia de los antígenos C, c, E y e del sistema Rh en donantes de sangre Rh negativos del Hemocentro Centro Oriente Colombiano. Métodos: Estudio descriptivo de corte transversal que incluyó 193 donantes voluntarios de sangre del Hemocentro Centro Oriente Colombiano, la fenotipificación de los antígenos del sistema Rh se realizó utilizando la técnica en tarjeta gel. Se calculó la frecuencia fenotípica de los antígenos del sistema Rh, en porcentajes y para el procesamiento de la información se utilizó el paquete estadístico SPSS versión 21.0 donde se realizó el análisis de los datos de la población. Como criterios de inclusión ser donante voluntario de sangre y de exclusión, estar hemoclasificado como antígeno DEL, D débil y D parcial. Resultados: Las muestras analizadas fueron obtenidas de la tubuladura central de la unidad fraccionada de glóbulos rojos, identificándose tres fenotipos con la siguiente frecuencia: cde/cde (95,86 por ciento), cde/cdE (3,10 por ciento) y cde/Cde (1,04 por ciento). Los participantes del estudio provenían de diversos municipios del departamento de Boyacá y otras regiones del país como llanos Orientales, Santander y Cundinamarca. Los antígenos del sistema Rh son altamente polimórficos a nivel de poblaciones, dada la importancia inmunológica de los antígenos del sistema Rh, los cuales se ven directamente relacionados con el desarrollo de anemia hemolítica postransfusional y perinatal, la fenotipificación ampliada brinda mayor seguridad transfusional y seguimiento al estado del feto o neonato(AU)

Introduction: The Rh system is composed of more than 56 antigens capable of producing hemolytic disease, defined by serological methods; being the most important and therefore the largest antigens of the system, the antigens D, C, c, E and e. These antigens are located on two proteins that are expressed in the membrane of erythrocytes Rh D and RhCE. Objective: To determine the frequency of the C, c, E and e antigens of the Rh system in Rh negative blood donors of Hemocentro Centro Oriente Colombiano. Methods: A cross-sectional descriptive study that included 193 blood donors from the Hemocentro Centro Oriente Colombiano, phenotyping the antigens of the Rh system, using the gel card technique. The phenotypic frequency of the Rh antigen was calculated, in percentages and for the processing of the information, the statistical package SPSS version 21.0 was used in Spanish where all the analysis of the population data was performed. With inclusion criteria to be a voluntary blood donor and exclusion, be hemoclasified as DEL antigen, weak D and partial D. Results: The analyzed samples were obtained from the central tubulant of the fractionated unit of red blood cells, three phenotypes were identified with a frequency of :cde / cde95.86 percent, cde / cdE 3.10 percent and cde / Cde 1, 04 percent; it was evidenced that the participants come from diverse municipalities of the department of Boyacá and other regions of the country like Eastern Plains, Santander and Cundinamarca. The Rh factor and the antigens of the Rh system are highly polymorphic at the population level, given the immunological importance of the antigens of the Rh system, which are directly related to the development of post transfusion hemolytic anemia and perinatal hemolytic disease, the extended phenotyping provides greater transfusional safety and follow-up to the status of the fetus or neonate(AU)

Hemolytic disease of newborn caused by multiple Rh antibodies

Hemolytic disease of Fetus and Newborn (HDFN) usually results due to natural occurring antibodies or alloimmunization in mother but the presence of multiple red cell antibodies increases the risk of development of significant HDFN. Here author reported a case of hemolytic disease of fetus and newborn in a preterm baby caused by multiple maternal antibodies. Direct Antiglobulin Test (DAT) on neonate blood sample was positive (3+) with monospecific DAT showed IgG type which was confirmed by heat elution. Antibody identification of eluate was done using commercial 11-cell panel by gel method showing specificity to anti-D and anti-C antibody which was differentiated from anti-G by sequential adsorption and elution studies. Neonate was treated with double volume exchange transfusion (DVET) using leucoreduced, irradiated O Rh D and C negative PRBC suspended in AB plasma and discharged 6th day in a stable condition. So, all pregnant women should be at least advised for ICT irrespective of Rh D negative status. If ICT is positive, they should be referred to higher center for proper Immunohematological work up, so that proper blood unit for DVET could be identified.

Distribution of RH and Kell (K) blood group antigens among blood donors in a tertiary care hospital of Jammu region, India

Background: Knowledge about the frequency of red cell antigen phenotype is very important for the creation of donor data bank and to minimize the risk of alloimmunization. This requires the determination of immunological characteristics of blood products and blood recipients by performing phenotyping of clinically significant blood group antigens. The aims and objectives were to study the distribution of Rh and Kell (K) antigen among blood donors of different ethnic groups in a tertiary care hospital.Methods: This was prospective observational cross sectional one-point analysis study which was carried out over a period of one year with effect from November 2015 to October 2016 in the Postgraduate Department of Immunohematology and Blood Transfusion Medicine, Shri Maharaja Gulab Singh (SMGS) Hospital, Government Medical College, Jammu and Kashmir, India. It comprised of voluntary and replacement donors and categorized into different ethnic groups i.e Dogras, Gujjar Muslims, Non-Gujjar Muslims, Kashmiri Pandits, Sikhs and Christian. Donors selection criteria was as per Drug and Cosmetic Act.Results: A total of 500 (Five hundred) blood samples from the donors of all blood groups were typed for the presence of Rh (D, C, E, c, e) and Kell (K) antigens. Out of these 500 samples, 420 were antigen typed by conventional tube technique and 80 samples were typed by column agglutination technique using glass beads. As per ethnicity, maximum donors were Dogras (74%) followed by Non-Gujjar Muslims (9.4%), Gujjar Muslims (9%), Sikhs (5.6%), Kashmiri Pandits (1.4%) and Christians were the least in frequency (0.6%). On phenotyping for Rh and Kell antigens ‘e’ antigen have the ubiquitous distribution and was found to have the highest frequency 486 (97.2%) followed by ‘D’ antigen 472 (94.4%), ‘C’ antigen 426 (85.2%), ‘c’ antigen 320 (64.0%) and ‘E’ antigen 103 (20.6%). Overall frequency of Kell (K) antigen was 2.6%.Conclusions: Knowledge of red cell antigen phenotype frequencies in a population with different ethnic groups can help in creating donor data bank and database for the distribution of blood groups for preparing inhouse cell panels and providing proper antigen compatible blood for patients with multiple alloantibodies and also reduce the risk of RBC antigen alloimmunization along with their complications.

Anticuerpos antiplaquetarios en pacientes cubanos en espera de trasplante renal / Platelet antibodies in cuban patients waiting for renal transplantation

Introducción: Los antígenos específicos de plaquetas, conocidos como antígenos de plaquetas humanas (HPA, del inglés human platelet antigens), se incluyen dentro del espectro de antígenos de histocompatibilidad no-HLA, debido a que los anticuerpos anti-HPA participan en el rechazo del trasplante, además de ser causa del fenómeno de refractariedad plaquetaria. Objetivo: Caracterizar los anticuerpos contra antígenos específicos de plaquetas en pacientes cubanos en espera de trasplante renal. Métodos: Se investigaron muestras de sangre de 901 pacientes mediante la técnica de inmovilización de antígenos plaquetarios con anticuerpos monoclonales. Resultados: En 78 pacientes se detectaron anticuerpos anti-HPA, que en el 87,17 por ciento reconocían los antígenos presentes en el complejo GP-IIb/IIIa. Estos anticuerpos fueron del tipo IgG en el 78,2 por ciento, IgA en el 11,53 por ciento e IgM en el 46,15 por ciento. Conclusiones: En pacientes cubanos en espera de trasplante renal son frecuentes los Ac anti-HPA, en su mayoría del tipo IgG dirigidos contra antígenos presentes en el complejo GP-IIb/IIIa(AU)

Introduction: Platelet-specific antigens, known as human platelet antigens (HPA), are included within the spectrum of non-HLA histocompatibility antigens, because HPA antibodies participate in the rejection of transplantation, besides being a cause of the phenomenon of platelet refractoriness. Objective: To characterize antibodies against platelet-specific antigens in Cuban patients awaiting kidney transplantation. Methods: The technique monoclonal antibodies immobilized platelets antigens was applied to blood samples from 901 patients. Results: HPA antibodies were detected in 78 patients, which in 87.17 percent recognized the antigens present in the GP-IIb / IIIa complex. These antibodies were in 78.2 percent of the IgG class, in 11.53 percent IgA and IgM in 46.15 percent. Conclusions: HPA antibodies, mostly of the IgG class and directed to antigens present in the GP-IIb/IIIa complex, are common in Cuban patients awaiting kidney transplantation(AU)

Red Blood Cell Alloimmunization in Korean Patients With Myelodysplastic Syndrome and Liver Cirrhosis

Red blood cell (RBC) alloimmunization varies across human populations and ethnic groups. We evaluated the characteristics of RBC alloimmunization and compared the risk of alloimmunization in Korean patients with myelodysplastic syndrome (MDS) and liver cirrhosis (LC), two representative diseases in which chronic transfusion is required. In total, 115 MDS patients and 202 LC patients transfused with RBCs between 2013 and 2015 were retrospectively included. Twenty patients (6.3%) were newly alloimmunized (five MDS patients, 4.3%; 15 LC patients, 7.4%). The median number of RBC units transfused in alloimmunized patients was nine (interquartile range, 4–15 units). As the number of transfused RBC units increased, the cumulative risk of alloimmunization was higher in LC than in MDS patients (P=0.001). The most common alloantibody detected in patients was anti-E (45%), followed by anti-c (17%), anti-e (10%), anti-C (7%), anti-Fyb (7%), and anti-Jka (7%). The present data indicate the need for matching of extended RBC antigens (Rh, Duffy, and Kidd systems) for chronically transfused patients with MDS and LC in Korea.

Prevalence of Unexpected Antibodies in Pregnant Korean Women and Neonatal Outcomes / 대한수혈학회지

BACKGROUND: In pregnant women, the frequency of irregular antibodies that cause hemolytic disease of the fetus and newborn (HDFN) vary between study populations. The clinical manifestations of HDFN differ according to the specificities and degree of irregular antibodies. This study examined the frequency and nature of maternal alloimmunization and neonatal outcomes. METHODS: Pregnant women, who underwent irregular antibody screening for prenatal testing at an obstetrics clinic in a single center, were enrolled. Those who screened positive for irregular antibodies were selected as the test group, and age- and obstetrics history-matched pregnant women were selected as the control group to evaluate the pregnancy outcomes according to irregular antibodies. RESULTS: The prevalence of irregular antibodies was 2.78% (42/1,508). With the exception of an unidentified antibody, anti-D was the most frequently identified antibody, followed in order by anti-E and anti-Le(a). The rate of fetal death was higher in the test group (6/37, 16.2%) than in the control group (1/37, 2.7%) (P=0.047). Eight pregnant women had anti-C or anti-D, one woman had a stillbirth, and four living neonates developed hyperbilirubinemia. Of six pregnant women with anti-E alone or with other alloantibodies, three experienced a spontaneous abortion or stillbirth. Among the six newborns with maternal anti-Le(a) and anti-Jk(a), four developed hyperbilirubinemia, but their mothers did not experience a spontaneous abortion or stillbirth. CONCLUSION: The prevalence of unexpected antibodies among pregnant Korean women was 2.78%. A significant difference in neonatal outcomes was observed, including the death rate, prematurity, and hyperbilirubinemia, depending on the specificity of the unexpected antibody.

Incidence of Red Blood Cell Alloantibody Formation after Platelet Concentrate Transfusions / 대한수혈학회지

BACKGROUND: In platelets transfusion, alloimmunization against the HLA and HPA antigen present in the white blood cells/platelets of the donor blood occurred. In addition, unexpected red blood cell alloantibodies might be produced by the alloimmunization of red blood cells antigens in the transfused platelet component. Therefore, this study examined the incidence of red blood cell alloantibodies after platelet transfusion. METHODS: From January to December 2018, adult patients who requested platelet concentrates or single donor platelets were enrolled. The results of pre/post-transfusion test, including antibody screening test and antibody identification test, were collected the incidence of red blood cell alloantibody formation was then analyzed, retrospectively. RESULTS: A total of 685 patients received 11,894 units of platelet concentrates and 1,402 units of single donor platelets. The median patient age was 64 years and the number of blood transfusions was 4.1. The amount of transfusion per session was 7.3 units, and the total transfused platelet concentrates was 30.9 units. New red blood cell alloantibodies were detected in 0.9% of all patients, and the identification results were observed as unidentified non-specific antibody in 66.7% and anti-E antibodies in 33.3%. The incidence of alloantibody was proportional to the frequency and amount of platelet transfusion. CONCLUSION: This paper reported the incidence of red blood cell alloantibody after platelet transfusion for the first time in Korea. Although matched platelet concentrates supply may be not practical in terms of cost-effectiveness, it may be useful to recognize the possibility of red blood cell alloimmunization and expand the understanding of extended matching transfusion.

Red blood cell alloimmunization among hospitalized patients: transfusion reactions and low alloantibody identification rate

ABSTRACT Background: Unexpected red blood cell alloantibodies can cause hemolytic transfusion reactions. In this study, the prevalence of alloimmunization, the rate of identification of alloantibodies and the rate of blood transfusion reactions among transfused patients were identified in a clinical emergency hospital in Brazil. Methods: Transfusions and clinical records of patients who had a positive indirect antiglobulin test between January and December 2013 were analyzed. Results: Of 1169 patients who received blood transfusions, 28 had positive indirect antiglobulin tests, with one patient having two positive tests at different times, resulting in 29 positive tests during the period of this study. Alloantibodies were identified in 58.6% (17/29) of the cases. In 27.5% (8/29), identification was inconclusive and it was not possible to confirm alloimmunization. The rate of red blood cell alloimmunization was 1.71% (21/1169). Of 21 cases of alloimmunization, four (19%) were unidentified due to an unusual agglutination profile. All identified alloantibodies were clinically significant (10/17 anti-Rh, 5/17 anti-Kell and 2/17 anti-MNS). In two patients who had positive indirect antiglobulin tests, one had an unidentified alloantibody, and the other had an inconclusive test and developed a hemolytic transfusion reaction. Conclusion: The prevalence of clinically important red blood cell alloantibodies and hemolytic transfusion reactions among patients with unidentified alloantibodies suggests that specific laboratory techniques should be performed to identify alloantibodies in cases of pan-reactivity or autoantibodies to improve transfusion safety.

Frecuencia de fenotipos del sistema Rh en donantes voluntarios de sangre / Frequency of Rh system phenotypes in voluntary blood donors / Frequência de fenótipos do sistema Rh em doadores de sangue voluntários

El sistema Rh es altamente polimórfico y está relacionado con la producción de aloanticuerpos y la enfermedad hemolítica del recién nacido. Los antígenos codificados por los genes RHD y RHCE forman el fenotipo Rh que es característico en cada población. Las variantes RHCE no han sido identificadas en la población ecuatoriana y así constituyen un riesgo de aloinmunización durante el embarazo o en transfusiones de componentes sanguíneos incompatibles. Prueba de ello es el estudio realizado en Ecuador que determinó una aloinmunización del 0,27%. Los anticuerpos con mayor frecuencia pertenecían al sistema Rh, resultados que motivaron la realización del presente estudio. Se analizaron un total de 1.298 muestras de donantes de sangre provenientes de 22 provincias ecuatorianas. Para la fenotipificación se utilizaron antisueros comerciales de la casa BIORAD y células de fenotipo conocido para el control de calidad interno, y se identificaron 20 fenotipos del sistema Rh distribuidos de forma heterogénea en las 22 provincias; el más frecuente fue Rz/R0. En donantes con fenotipo D débil el más común fue el R2/r, mientras que en los donantes Rh(D) negativo fue el fenotipo r/r. Estos datos demuestran la variedad de fenotipos en la población ecuatoriana y por ende la necesidad de su detección oportuna.

The Rh system is highly polymorphic. It is related to the production of alloantibodies and the hemolytic disease of the newborn. The antigens encoded by the RHD and RHCE genes form the Rh that is characteristic for each population. The RHCE variants have not been identified in the Ecuadorian population, constituting a risk of alloimmunization during pregnancy or in transfusions of incompatible blood components. Proof of this is the study carried out in Ecuador that determined an alloimmunization of 0.27% and the antibodies, more frequently belonged to the Rh system, results that motivated the realization of the present study. A total of 1298 samples from blood donors from 22 Ecuadorian provinces were analyzed. For the phenotyping, commercial antisera from the BIORAD house were used and cells of known phenotype for internal quality control. Identifying 20 phenotypes of the Rh system distributed heterogeneously in the 22 provinces, the most frequent was Rz/R0. In donors with weak D phenotype the most common was R2/r; whereas in Rh(D) negative donors was the r/r phenotype, these data demonstrate the variety of phenotypes in the Ecuadorian population and therefore the need for their timely detection.

O sistema Rh é altamente polimórfico e está relacionado com a produção de aloanticorpos e a doença hemolítica do recém-nascido. Os antígenos codificados pelos genes RHD e RHCE formam o fenótipo de Rh, que é característico para cada população. As variantes de RHCE não foram identificados na população equatoriana constituindo um risco de aloimunização durante a gravidez ou em transfusões de componentes sanguíneos incompatíveis. Prova disso é o estudo realizado no Equador que determinou aloimunização de 0,27%. Os anticorpos com maior frequência pertenciam ao sistema Rh, resultados que motivaram a realização do presente estudo. Um total de 1298 amostras de doadores de sangue de 22 estados equatorianos foram analisadas. Utilizou-se para a fenotipificação anti-soros comerciais BIORAD e células de fenótipo conhecido para controle de qualidade interno, identificando-se 20 fenótipos do sistema Rh heterogeneamente distribuídos nos 22 estados. O mais frequente foi Rz/R0. Em doadores com fenótipo D fraco, o mais comum foi o R2/r; ao passo que nos doadores Rh (D) negativo foi o fenótipo r/r. Esses dados demonstram a variedade de fenótipos na população do Equador, e portanto a necessidade da detecção precoce dos mesmos.

Clinical and epidemiological profile of alloimmunized and autoimmunized multi-transfused patients against red blood cell antigens in a blood center of Minas Gerais

ABSTRACT Background: The large diversity of red blood cell antigens favors, especially in multi-transfused patients, the occurrence of autoimmunization and alloimmunization with the risk of hemolytic transfusion reactions. Thus, this study aimed to determine the rates of alloimmunization and autoimmunization in these individuals, as well as the types of alloantibodies and their systems, clinical and epidemiological aspects and the frequency of autoimmunity in alloimmunized and non-alloimmunized patients. Methods: In a retrospective study, 153 multi-transfused patients from 2006 to 2014 were evaluated. Sixty-eight had onco-hematological diseases, 64 had hemoglobinopathies and 21 had chronic renal failure. Descriptive analyses were carried out with the proportions being compared using the chi-square test, with the significance level set at 5%. Results: The Rh system was the most frequently involved (53.11%) and anti-E and anti-K (Kell system) were the most prevalent alloantibodies (21.87% each). Autoantibodies were found in ten patients (6.54%) with the percentages of autoimmunization in alloimmunized and non-alloimmunized individuals being 29.16% and 2.32%, respectively (p = 0.0001). There was a significant difference between autoimmunization and the number of transfusions (16.21% in 6-10 vs. 5.26% <6 vs. 2.56% >10; p = 0.0203) and diseases (19.04% in chronic renal failure vs. 6.25% in hemoglobinopathies vs. 2.94% in onco-hematological diseases; p = 0.0329). Conclusion: The results show a strong correlation between alloimmunization and autoimmunization. Moreover, they reinforce the need for further studies on the clinical and epidemiological profile of multi-transfused patients in relation to alloimmunity and autoimmunity, especially the latter, for a better understanding of its etiopathogenesis and physiopathogenesis.

Transfusion management for patients taking an anti-CD38 monoclonal antibody

Abstract Introduction: Pre-transfusion tests, essential for the release of blood components, may be affected by drugs. Monoclonal antibodies represent a class of medications increasingly used in the clinical practice, with anti-CD38 monoclonal antibodies (daratumumab) being a promising resource in the treatment of refractory myeloma. This monoclonal antibody recognizes CD38 in myeloma cells and interferes with pre-transfusion tests by causing panreactivity in indirect antiglobulin tests thereby clinically masking alloantibodies. Dithiothreitol is a reagent that breaks disulfide bonds and effectively destroys antigenic sites for CD38 on red blood cells. This study reports the immunohematological findings of pre-transfusion tests of patients with multiple myeloma receiving daratumumab and on solutions to prevent the interference of this monoclonal antibody. Methods: Serum samples from five patients on anti-CD38 monoclonal antibody treatment were evaluated. Tests performed included ABO/RhD typing, indirect antiglobulin test, direct antiglobulin test and eluate test. A daily evaluation was performed to determine the shelf life of dithiothreitol-treated red blood cells when stored in Alsever's solution. Results: No interference in the ABO/RhD typing results was noted but in all samples, a panreactivity was observed in indirect antiglobulin tests. Regarding the direct antiglobulin test, two samples presented positive results but negative eluates. In all samples, treatment of reagent red blood cells with 0.2 M dithiothreitol offset interference by anti-CD38 monoclonal antibodies. Dithiothreitol-treated red blood cells stored in Alsever's solution were stable for up to 15 days. Conclusion: Treatment of reagent red blood cells with dithiothreitol can be efficient and accessible to offset the interference of the anti-CD38 drug in pre-transfusion tests. The number of costly serological workups can be reduced by having stored dithiothreitol red blood cells with this proving to be a useful reagent for investigating anti-CD38.