Non-RhD alloimmunization in pregnancy: an updated review

Abstract RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be associated with the occurrence of this phenomenon and that have been growing in proportion, given that current prevention strategies focus only on anti-RhD antibodies. Although not widespread, the screening and diagnostic management of the disease caused by these antibodies has recommendations in the literature. For this reason, the following review was carried out with the objective of listing the main red blood cell antigen groups described — such as Rh, ABO, Kell, MNS, Duffy, Kidd, among others — addressing the clinical importance of each one, prevalence in different countries, and recommended management when detecting such antibodies during pregnancy.

TO DETERMINE FETOMATERNAL OUTCOME IN RH NEGATIVE PREGNANCY

Background: The present study was conducted to determine the fetomaternal outcome among Rh-negative pregnancies presenting to a secondary care hospital of North India. Methods: A prospective observational design was carried out among Rh negative mothers presenting to the Department of Obstetrics and Gynecology of Swaroop Rani Hospital, Prayagraj, from December 2021 to July 2022. On admission each mother was interviewed using a questionnaire. ABO/Rh grouping of the mothers as well as their husbands/partners were done. Rh antibody titers of the patients were done at first visit and repeated at 28 and 32 weeks respectively. The labor of each of the mothers was monitored carefully, with the mode of delivery and outcome of labor being recorded in the proforma. For the Rh typing of the neonate, cord blood was collected after delivery and sent for ABO/Rh grouping. Both the mother and the neonate were followed up till their discharge/death, and any adverse maternal or neonatal outcome in this period were noted. Results: During the study period, 46 mothers were assessed. The mean age was 23.9±1.4 years. Most of the mothers were multipara. 4.4% of them had a raised Rh antibody titer. Of the mothers, 13% delivered preterm and most required lower segment cesarean section (56.5%). 93.5% of the deliveries resulted in live births. The incidence of Rh incompatibility among the Rh-negative mothers was 83.7%. The mean birth weight was 2.8±0.4 kgs, with most of the babies being male (60.5%). The most common complications developing in the neonates was anemia (21%) and neonatal hyperbilirubinemia (9.3%). Only one (2.3%) of the neonates born to the mothers died due to post-birth complications. Conclusions: Rh incompatibility was observed to be high among the mothers assessed in the study, with 4.4% having raised anti-D titers. Anemia and neonatal hyperbilirubinemia were found to be the most common problems associated with such pregnancies.

Isoinmunización Rh en bajas respondedoras: Reporte de caso / Rh Isoimmunization in Low Responders: Case Report / Isoimunização Rh em pacientes com baixa resposta: relato de caso

Introducción. La isoinmunización Rh consiste en la producción de anticuerpos maternos en una gestante Rh negativa contra los antígenos de los eritrocitos Rh positivos fetales ocasionados por una hemorragia fetomaterna. En población gestante, el 15% son Rh negativo y la severidad de la afectación fetal está relacionada con una serie de procesos inmunológicos y la historia obstétrica. Si una gestante Rh negativa con riesgo de isoinmunización no recibe profilaxis con inmunoglobulina Anti-D se inmuniza el 16% en la primera gestación, el 30% en la segunda y el 50% después de la tercera. Con este reporte de caso queremos describir el subgrupo de pacientes gestantes con isoinmunización Rh bajas respondedoras. Presentación del caso. G9P5C1A2Gem1V7 de 43 años, remitida en semana 30 de gestación por isoinmunización Rh, no recibió inmunoglobulina Anti-D durante este embarazo, ni en los anteriores ni en el posparto, reporte de Coombs indirecto de 1/4 que se eleva a 1/16, seguimiento ecográfico normal. En semana 35.3 presenta anemia fetal leve y por tratarse de un embarazo alrededor del término se finaliza por cesárea. Recién nacido con adecuado peso para la edad gestacional, quien fue dado de alta a las 72 horas con evolución satisfactoria. Discusión. Las gestantes con isoinmunización Rh bajas respondedoras se sensibilizan con altos volúmenes sanguíneos sin repercusión hemodinámica in utero, produciendo una enfermedad hemolítica fetal leve. Esta respuesta inmune es poco frecuente y está asociada a factores protectores; sin embargo, son necesarios más estudios que sustenten esta condición. Conclusiones. El control prenatal y el Coombs indirecto cuantitativo seriado son las principales herramientas para la prevención de la isoinmunización. El conocimiento de la respuesta inmunológica permite identificar el subgrupo de las bajas respondedoras que tienen una evolución clínica más leve y menor morbilidad neonatal. Palabras clave: Embarazo; Isoinmunización Rh; Eritroblastosis Fetal; Globulina Inmune RHO(D); Hidropesía Fetal.

Introduction. Rh isoimmunization consists of a Rh-negative pregnant woman producing maternal antibodies against the antigens of fetal Rh-positive erythrocytes due to fetomaternal hemorrhage. 15% of the pregnant population is Rh negative, and the severity of fetal effects is related to a series of immunological processes and the obstetric history. If a Rh-negative pregnant woman at risk of isoimmunization does not receive a prophylaxis of Anti-D immunolobulin, 16% are immunized in the first pregnancy, 30% in the second and 50% after the third. In this case report we will describe the subgroup of low responder pregnant patients with Rh isoimmunization. Case Presentation. G9P5C1A2Gem1V7, 43 years old, referred on the 30th week of pregnancy due to Rh isoimmunization. She did not receive Anti-D immunolobulin during this pregnancy, nor in her previous pregnancies, nor during postpartum. Indirect Coombs report of 1/4, which increases to 1/16. Ultrasound monitoring is normal. At week 35.3 she presented mild fetal anemia, and because the pregnancy was near its term, it was ended by cesarean section. Newborn with adequate weight considering the gestational age, who was then discharged after 72 hours with satisfactory evolution. Discussion. Low responder pregnant women with Rh isoimmunization are sensitized with high blood volumes but without hemodynamic repercussions in utero, producing a mild fetal hemolytic disease. This immune response is infrequent and is associated with protective factors; however, further studies are required to support this condition. Conclusions. Prenatal control and serialized quantitative indirect Coombs testing are the main tools for the prevention of isoimmunization. Knowledge of the immunological response enables identifying the subgroup of low responders who present a milder clinical evolution and lower newborn morbidity. Keywords: Pregnancy; Rh Isoimmunization; Erythroblastosis, Fetal; RHO(D) Immune Globulin; Hydrops Fetalis.

Introdução. A isoimunização Rh consiste na produção de anticorpos maternos em uma gestante Rh negativa contra os antígenos dos eritrócitos fetais Rh positivos causados por hemorragia fetomaterna. Na população gestante, 15% são Rh negativos e a gravidade do envolvimento fetal está relacionada a uma série de processos imunológicos e ao histórico obstétrico. Se uma gestante Rh negativa com risco de isoimunização não receber profilaxia com imunoglobulina Anti-D, imuniza-se 16% na primeira gestação, 30% na segunda e 50% após a terceira. Com este relato de caso, queremos descrever o subgrupo de pacientes gestantes com isoimunização Rh de baixa resposta. Apresentação do caso. G9P5C1A2Gem1V7, 43 anos, encaminhada na 30ª semana de gestação para isoimunização Rh, não recebeu imunoglobulina Anti-D nesta gestação, nem nas anteriores nem no puerpério, laudo de Coombs indireto de 1/4 que sobe para 1/16, acompanhamento ultrassonográfico normal. Na semana 35,3, apresentou anemia fetal leve e por se tratar de uma gestação próxima ao termo, foi interrompida por cesariana. Recém-nascido com peso adequado para a idade gestacional, que recebeu alta às 72 horas com evolução satisfatória. Discussão. Gestantes com isoimunização Rh de baixa resposta são sensibilizadas com elevados volumes sanguíneos sem repercussões hemodinâmicas in utero, produzindo doença hemolítica fetal leve. Essa resposta imune é rara e está associada a fatores protetores; no entanto, mais estudos são necessários para fundamentar esta condição. Conclusões. O controle pré-natal e o Coombs indireto quantitativo seriado são as principais ferramentas para a prevenção da isoimunização. O conhecimento da resposta imunológica permite identificar o subgrupo de pacientes com baixa resposta que apresentam evolução clínica mais branda e menor morbidade neonatal. Palavras-chave: Gravidez; Isoimunização Rh; Eritroblastose Fetal; Inmunoglobulina RHO (D), Hidropisia Fetal.

Use of prophylactic phototherapy for RhD neonatal disease in a referral service

Abstract Objective: This study aimed to describe the effect of prophylactic phototherapy in the treatment of infants with Neonatal Hemolytic Disease. Method: A retrospective cohort study was carried out with 199 RhD-positive infants, born to RhD-negative mothers, alloimmunized for RhD antigen, between January 2009 and December 2018. Results: The incidence of exchange transfusions in the study population was 9.5%, with a mean maximum bilirubin value of 11.3 mg % (± 4.3mg %). Bilirubin's maximum peak was achieved with a mean of 119.2 life hours (± 70.6h). Conclusions: The low incidence of exchange transfusion, the extended maximum bilirubin peak for later ages, and the low mean of the maximum bilirubin values may indicate a positive effect of prophylactic phototherapy in the treatment of this disease. Further studies must be carried out to confirm these findings.

Descripción de una población de embarazadas con incompatibilidad Rh (D) / Description of a population of pregnant women with Rh (D) incompatibility

Resumen OBJETIVO: Describir los desenlaces maternos y perinatales en embarazadas con incompatibilidad Rh D. MATERIALES Y MÉTODOS: Estudio de cohorte retrospectiva efectuado en la Unidad Materno Infantil de Medellín, Colombia, en pacientes embarazadas atendidas entre 2013 y 2018 con incompatibilidad Rh. Se realizó un muestreo no probabilístico de casos consecutivos y un análisis univariado. RESULTADOS: Se incluyeron 250 pacientes con mediana de edad de 26 años y tipo de sangre O-, que fue el más prevalente (55.2%). El 49.2% de las pacientes había tenido entre 2 y 3 embarazos previos. El 88% de las pacientes no había tenido ningún evento sensibilizante durante el embarazo. El 65.2% tuvo un reporte negativo del primer Coombs y la media de semanas de embarazo al primer Coombs fue de 28. El 48% de las pacientes recibió la inmunoglobulina G anti-D a una mediana de 28 semanas de gestación. CONCLUSIÓN: El estudio confirma datos clínicos y sociodemográficos y sugiere que se requiere fortalecer la oportunidad en la captación temprana de las pacientes para el seguimiento con el Coombs y para la indicación de la profilaxis.

Abstract OBJECTIVE: To determine the maternal and fetal outcomes in pregnant women with Rh D incompatibility. MATERIALS AND METHODS: A Retrospective cohort study carried out in the Maternal and Child Unit of Medellín, Colombia, in pregnant patients attended between 2013 and 2018. RESULTS: 250 patients were included, in which the median age was 26 years. The O- blood type was the most prevalent in pregnant women with 55.2% and 49.2% of the patients had had between 2 and 3 previous pregnancies, in addition, 88% of the patients had not presented any sensitizing event during her pregnancy. 65.2% had a negative first Coombs result and the mean gestational age of the first Coombs was 28 weeks. 48% of patients received immunoglobulin G anti D at a median gestational age of 28 weeks. CONCLUSION: The present study confirms the clinical and sociodemographic data, however it suggests that it may be necessary to strengthen the opportunity in the early recruitment of patients for follow-up with Coombs and for the indication of prophylaxis.

Hidropesía fetal y enfermedad hemolítica del feto y el recién nacido / Hydrops Fetalis and Hemolytic Disease of the fetus and the newborn. Update

Introducción: la enfermedad hemolítica del feto y el recién nacido (EHFRN) consiste en la incompatibilidad presente entre los antígenos eritrocitarios maternos y los fetales, que desencadena en la madre una reacción inmunitaria contra los eritrocitos fetales produciendo su destrucción. La complicación más grave es la hidropesía fetal, la cual consiste en síntomas de origen hemodinámico, derivados de una falla cardíaca por la disminución en el aporte de oxígeno o por la falta de producción de albúmina. Objetivo: realizar una revisión actualizada de la EHFRN, exponiendo principalmente la hidropesía fetal como una de sus grandes complicaciones. Metodología: se realizó una revisión bibliográfica desde 2018 hasta 2021 en bases de datos tales como Science Direct, Pubmed y Medline con base en los siguientes términos MeSH: anemia hemolítica, isoinmunización Rh, eritroblastosis fetal, hidropesía fetal. Conclusión: la EHFRN es una causa frecuente de enfermedad hemolítica grave en estos pacientes, pero gracias a la Inmunoglubulina G anti-D se ha logrado prevenir la mayoría de casos de incompatibilidad Rh. Sin embargo, la hidropesía fetal presenta una alta mortalidad, lo cual hace importante promover un diagnóstico oportuno y el uso de profilaxis

Introduction: Hemolytic disease of the fetus and newborn (EHFRN) consists of the incompatibility present between maternal and fetal erythrocyte antigens, which triggers an immune reaction in the mother against fetal erythrocytes, causing their destruction. The most serious complication is hydrops fetalis, which consists of symptoms of hemodynamic origin, derived from heart failure due to the decrease in oxygen supply or the lack of albumin production. Objective: Make an updated review of the EHFRN, exposing mainly hydrops fetalis as one of its major complications. Methodology: Bibliographic review was carried out from 2018 to 2021 in databases such as Science Direct, Pubmed and Medline based on the following MeSH terms: hemolytic anemia, Rh isoimmunization, erythroblastosis fetalis, hydrops fetalis. Conclusion: EHFRN is a frequent cause of severe hemolytic disease in these patients; but thanks to the anti-D Immunoglobulin G, the majority of cases of Rh incompatibility have been prevented. However, hydrops fetalis has a high mortality rate, which makes it important to promote timely diagnosis and the use of prophylaxis

Preventing Rh alloimmunization during pregnancy: interpretation of clinical guidelines / 中华围产医学杂志

Rh alloimmunization can lead to serious fetal complications, such as hemolysis, anemia, edema, and even intrauterine death. However, there is no domestic clinical guideline for prophylaxis and management of Rh alloimmunization. This review aims to interpret the key points from international clinical guidelines, consisting of the timing of routine antibody screening and anti-Rh(D) immunoglobulin prophylaxis strategies for Rh-negative pregnant women, possible sensitization events and anti-D prophylaxis of Rh alloimmunization, and postpartum prophylaxis for unsensitized Rh-negative pregnant women.

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.

Non RhD isoimmunization causing severe hemolytic disease of fetus and newborn in Rh positive pregnancies: report of 2 cases with review of literature

Anti D immunoprophylaxis widespread use in antenatal patients has led to dramatic reduction in the rates of alloimmunization due to anti D, which is the most common Rh antibody causing severe Hemolytic Disease of Fetus and New born (HDFN). However, there has been increase in the rates of non Rh D antibodies causing alloimmunization in pregnant women and leading to moderate to severe HDFN. We hereby report two cases of neonates presenting with moderate to severe HDFN with strongly positive DAT due to Rh anti-c antibody in Rh-positive mothers. Thus, antenatal antibody screening should be done in all Rh-positive pregnant women to prevent the diagnostic delay of HDFN occurring due to Non anti-D isoimmunization in the fetus.

Research progress in hemolytic disease in fetuses and newborns: a review / 中华围产医学杂志

Hemolytic disease in fetuses and newborns (HDFN) is a common perinatal condition caused by the destruction of erythrocytes of neonates or fetuses by maternal IgG antibodies. Fetal or neonatal hemolysis is HDFN's primary pathological process resulting in anemia and neonatal jaundice. This review summarized recent progress in the pathophysiology of HDFN, the clinical correlation between anti-erythrocyte alloantibodies and HDFN, laboratory tests for alloimmunization in pregnancy, clinical evaluation of high-risk cases of HDFN, and treatment and prevention of HDFN at home and abroad.

Research progress in hemolytic disease in fetuses and newborns: a review / 中华围产医学杂志

Hemolytic disease in fetuses and newborns (HDFN) is a common perinatal condition caused by the destruction of erythrocytes of neonates or fetuses by maternal IgG antibodies.Fetal or neonatal hemolysis is HDFN's primary pathological process resulting in anemia and neonatal jaundice.This review summarized recent progress in the pathophysiology of HDFN,the clinical correlation between anti-erythrocyte alloantibodies and HDFN,laboratory tests for alloimmunization in pregnancy,clinical evaluation of high-risk cases of HDFN,and treatment and prevention of HDFN at home and abroad.

Impacto en el diagnóstico temprano de la enfermedad hemolítica del recién nacido en neonatos mayores de 2kg mediante el tamizaje de la bilirrubinas por método transcutáneo / Impact in the early diagnosis of hemolytic disease of the newborn in neonates greater than 2kg by screening bilirubins by transcutaneous method

Introducción: La enfermedad hemolítica del recién nacido es una afección inmunológica autoinmunitaria en la cual la vida del hematíe es acortada como resultado por la acción de anticuerpos maternos. La gravedad de la enfermedad se asocia a anemia, trombocitopenia, muerte fetal intraútero, kernicterus, defectos en la coagulación, hipoglicemia, ascitis e hydrps. El objetivo de este estudio fue comparar el impacto de la implementación de intervenciones para el diagnóstico de esta patología en el servicio de neonatología del Hospital del Niño. Materiales y métodos: Se evaluó recién nacidos de la maternidad del Hospital Santo Tomás> 2 kg con diagnóstico de isoinmunización (ABO o Rh) en dos períodos, antes y después de la implementación del tamizaje de las bilirrubinas por método transcutáneo desde 1 enero 2015 a 31 diciembre 2016; se tomó en cuenta el tipo de isoinmunización, la edad al momento del diagnóstico, días de fototerapia que recibe, días intrahospitalarios, uso de inmunoglobulinas y complicaciones, se obtiene valor de P para comparar un período con otro y evaluar su significancia . Resultados: Se obtienen 460 pacientes; 230 para cada período. Cumplen con los criterios de inclusión un total de 422 pacientes (203 para el primer periodo y 219 para el segundo). Entre los resultados se observó que un 95.6% la incompatibilidad de grupo ABO predominó sobre la isoinmunización Rh en ambos períodos; con leve prevalencia de la isoinmunización OA. La bilirrubinas séricas al momento del ingreso a sala de neonatología 2 disminuyó> 5 mg/dl en el segundo periodo (13.27 y 8.05 respectivamente) y en cuanto a los días de fototerapia se encontró disminución de 4.2 días para el primer período y 2.6 días en el segundo período, lo mismo que la estancia intrahospitalaria de 5.2 a 2.8 días. La edad al momento del diagnóstico disminuyó de 33.8horas a 15.4 horas en el segundo periodo y la frecuencia de exanguino-transfusiones disminuyó de 6.9% a 2.3% en el segundo periodo. Conclusión: Se observó la captación temprana de pacientes con enfermedad hemolítica del recién nacido, disminuyendo la duración de estancia intrahospitalaria.

Introduction: The hemolytic disease of the newborn is an autoimmune immunological condition in which the life of the erythrocyte is shortened as a result of the action of maternal antibodies. The severity of the disease is associated with anemia, thrombocytopenia, intrauterine fetal death, kernicterus, coagulation defects, hypoglycemia, ascites and hydrps. The objective of this study was to compare the impact of the implementation of interventions for the diagnosis of this pathology in the neonatology service of the Hospital del Niño. Materials and methods: Newborn infants from Santo Tomás Hospital> 2 kg were evaluated with diagnosis of isoimmunization (ABO or Rh) in two periods, before and after the implementation of bilirubin screening by transcutaneous method from January 1, 2015 to December 31, 2016; the type of isoimmunization, age at diagnosis, days of phototherapy received, hospital days, use of immunoglobulins and complications were taken into account, P value is obtained to compare one period with another and evaluate its significance. Results: 460 patients are obtained; 230 for each period. A total of 422 patients met the inclusion criteria (203 for the first period and 219 for the second). Among the results, it was observed that 95.6% of ABO group incompatibility predominated over Rh isoimmunization in both periods; with mild prevalence of OA isoimmunization. Serum bilirubins at the time of admission to neonatal ward 2 decreased> 5 mg / dl in the second period (13.27 and 8.05 respectively) and in terms of the days of phototherapy a decrease of 4.2 days was found for the first period and 2.6 days in the second period, as well as the inpatient stay from 5.2 to 2.8 days. The age at the time of diagnosis decreased from 33.8 hours to 15.4 hours in the second period and the frequency of exanguine-transfusions decreased from 6.9% to 2.3% in the second period. Conclusion: Early uptake of born with hemolytic disease was observed, decreasing the duration of in-hospital stay.

Anemia hemolítica fetal rápidamente progresiva en el pretérmino tardío: reporte de caso / Rapidly progressive fetal hemolytic anemia in the late preterm: case report and literature review

Resumen ANTECEDENTES: La isoinmunización Rh es el principal factor de riesgo de anemia fetal. Cuando ésta es moderada o severa la transfusión intrauterina antes de las 34 semanas, y el nacimiento del feto luego de las 37, son las opciones de tratamiento más aceptadas. CASO CLÍNCO: Paciente de 29 años, con 34 semanas de embarazo, con antecedentes de tres gestaciones que terminaron en dos partos y una cesárea e isoinmunización Rh con secuela neurológica por anemia hemolítica. Hallazgo de Coombs indirecto positivo 1/512 y velocidad pico sistólica de la arteria cerebral media de 57 cm/s. Registro cardiotocográfico reactivo y seguimiento ambulatorio semanal. Retornó a Urgencias debido a la percepción de contracciones uterinas esporádicas. El feto se encontró con 140 lpm, peso de 2760 g y cuantificaciones correspondientes a anemia leve. La cordocentesis reportó Hb = 7.7 g/dL; "O" Rh (+). El embarazo terminó mediante cesárea con el nacimiento de una niña de 2702 g, Apgar 9/9, hemoglobina neonatal de 7.9 y 7 g/dL, bilirrubina total de 6.8 y 10.71 mg/dL (a las 4 y 7 horas después del nacimiento). Se efectuó exanguinotransfusión en dos oportunidades por anemia recidivante, fototerapia intensiva durante 5 días, fue dada de alta a los 25 días. CONCLUSIONES: Es importante analizar y cuantificar los riesgos de prolongar el embarazo más allá de las 34 semanas y aplicar transfusión intrauterina versus interrumpirlo y continuar el tratamiento de forma extrauterina; después de las 35 semanas los riesgos de los procedimientos superan los del parto pretérmino.

Abstract BACKGROUND: Rh isoimmunization is the main risk factor for fetal anemia. When this is moderate or severe intrauterine transfusion before 34 weeks, and the birth of the fetus after 37, are the most accepted treatment options. CLINICAL CASE: A 29-year-old patient, 34 weeks pregnant, with a history of three pregnancies that ended in two deliveries and a C-section and Rh isoimmunization with neurological sequelae due to hemolytic anemia. Finding of positive indirect Coombs 1/512 and VPS-ACM = 57 cm/s. Reagent cardiotocographic record and weekly ambulatory follow-up. He returned to the Emergency Department due to the perception of sporadic uterine contractions. The fetus was found with 140 bpm, weight of 2760 g and quantifications corresponding to mild anemia. The cordocentesis reported Hb = 7.7 g/dL; "O" Rh (+). The pregnancy was terminated by caesarean section with the birth of a girl of 2702 g, Apgar 9/9, neonatal hemoglobin of 7.9 and 7 g/dL, total bilirubin = 6.8 and 10.71 mg/dL (at 4 and 7 hours after birth). Exchange transfusion was performed twice due to recurrent anemia, intensive phototherapy for 5 days, and was discharged after 25 days. CONCLUSIONS: It is important to analyze and quantify the risks of prolonging a pregnancy beyond 34 weeks and apply intrauterine transfusion versus interrupting it and continuing the treatment extrauterine; After 35 weeks, the risks of the procedures surpass those of preterm delivery.

Manejo de la embarazada con isoinmunización por anticuerpos irregulares / Pregnant management by isoimmunized irregular antibodies

La isoinmunización eritrocitaria feto-materna se define como la presencia de anticuerpos maternos dirigidos contra antígenos presentes en los glóbulos rojos fetales. Los anticuerpos maternos pueden atravesar la barrera placentaria y provocar hemólisis de los glóbulos rojos fetales produciendo anemia hemolítica e hiperbilirrubinemia, características de la enfermedad hemolítica perinatal (EHP). La principal causa de EHP es la incompatibilidad ABO, seguida de la isoinmunización por RhD; esta última ha disminuido su incidencia dado el amplio uso de inmunoglobulina anti D. Sin embargo, el glóbulo rojo tiene más de 400 antígenos, muchos de ellos (>50) capaces de producir isoinmunización y EHP. En este artículo, revisamos la evidencia y proponemos un algoritmo de manejo y seguimiento de las embarazadas con isoinmunización por anticuerpos irregulares. En la isoinmunización por anticuerpos irregulares, los títulos de anticuerpos maternos no se correlacionan con la gravedad de la enfermedad. La anemia en la EHP por anticuerpos anti-Kell es secundaria a una supresión de la eritroblastosis fetal a diferencia del resto de los sistemas que producen anemia hemolítica. Recomendamos efectuar tamizaje de todas las pacientes en el control prenatal, solicitando grupo sanguíneo, Rh y test de Coombs indirecto. En las pacientes Rh (+) con test de Coombs indirecto positivo es necesario identificar los anticuerpos irregulares. En caso de tener isoinmunización por anticuerpos irregulares con riesgo de EHP, derivar a una unidad de alto riesgo obstétrico para realizar seguimiento de la aparición de anemia fetal midiendo de modo seriado el peak sistólico de la arteria cerebral media. Si se detecta anemia fetal, debemos planificar una cordocentesis para confirmar el diagnóstico y tratar la anemia.

The fetomaternal erythrocyte isoimmunization is defined as the presence of maternal antibodies directed against antigens present in fetal red blood cells. Maternal antibodies can cross the placenta and cause hemolysis of fetal red blood cells causing hyperbilirubinemia and hemolytic anemia, known as perinatal hemolytic disease (PHD). The main cause of PHD is ABO incompatibility, followed by RhD isoimmunization. The latter has decreased its incidence since the widespread use of anti-D immunoglobulin. However, the red cell has more than 400 antigens; many of them (>50) can lead to isoimmunization and PHD. In this article, we review the evidence and propose an algorithm for the management and monitoring of pregnant women with irregular antibodies isoimmunization. In the isoimmunization by irregular antibodies, maternal antibody titers do not correlate with the severity of the disease. Anemia in PHD by anti-Kell is secondary to suppression of fetal erythroblastosis unlike other systems that produce hemolytic anemia. We suggest the screening of all patients in the prenatal control with blood group, Rh and indirect Coombs test. In the Rh (+) patients with positive indirect Coombs test, irregular antibodies should be identified. In case of immunization by irregular antibodies in risk of PHD, the women should be referred to a high-risk obstetrics where the appearance of fetal anemia should be seek by measuring systolic peak of middle cerebral artery. If anemia is detected full confirmation of diagnosis and treatment should be effected by cordocentesis.

Caracterización de la aloinmunización eritrocitaria en el Hospital Universitario del Valle entre 2011 y 2013 / Characterization of Red Blood Cells Alloimmunization at Hospital Universitario del Valle between 2011 and 2013 / Caracterização de aloimunização eritrocitária no Hospital Universitário do Valle no período de 2011 a 2013

Introducción: Las necesidades nacionales de sangre están parcialmente cubiertas. El uso de la sangre implica la detección e identificación de anticuerpos inesperados en los receptores de componentes eritrocitarios. Objetivo: Caracterizar demográfica y clínicamente los casos de aloinmunización eritrocitaria en el servicio transfusional del Hospital Universitario del Valle (HUV), Cali, Valle del Cauca, Colombia entre 2011 y 2013. Metodología: Se diseñó un estudio de corte transversal con los casos de aloinmunización eritrocitaria transfundidos por el servicio transfusional del HUV entre el 1 de agosto del 2011 hasta el 31 de julio del 2013. Los casos se incluyeron a través de un muestreo con asignación al azar sistemático. Para ingreso de datos y análisis se empleó el programa Epi-Info para Windows®. El estudio contó con aprobación del Comité de Ética. Resultados: Se incluyeron 80 casos de los cuales el 53.8% eran de género femenino y el 46.2% masculino. Además, el 65% correspondía a raza mestiza hispana y el 35% a afrodescendientes. El 22.5% tenía antecedentes de enfermedades hematopoyéticas y el 45% estaban hospitalizados por diagnósticos incluidos en esta categoría del CIE-10. El 79% de las mujeres tenían historia obstétrica. El 18.75% fueron transfundidos previamente. El 36% de los casos contaba con un fenotipo CceeK. El 31.25% tenían aloanticuerpo Anti-E, seguido por Anti-K con el 21.25%. Conclusiones: El principal aloanticuerpo identificado fue Anti-E seguido de Anti-K. Asimismo existe un grupo importante de pacientes en los cuales no se pudo identificar el aloanticuerpo asociado, debido principalmente a mezcla de anticuerpos. Además, la mayoría de los casos corresponde a adultos jóvenes y adultos. En relación con las características clínicas de la muestra se observó una representación discreta de las hemoglobinopatías congénitas y la mayoría no fueron politransfundidos previamente. [Pérez JA, Cortés A. Caracterización de la aloinmunización Eritrocitaria en el Hospital Universitario del Valle entre 2011 y 2013. MedUNAB 2014; 17(2):66-80].

Background: The national blood needs are partially covered. The use of blood involves the detection and identification of unexpected red cell receptor antibodies. Objective: The objective was to characterize demographically and clinically cases of erythrocyte alloimmunization at Transfusion Service of the University Hospital of the Valle (Cali, Valle del Cauca) between 2011 and 2013. Methodology: A cross-sectional design of cases th of red cell alloimmunization transfused between august 1th 2011 until july 31th 2013. The cases were included through a systematic random sampling. Epi-Info for Windows® was used for the development of the instrument, data entry and statistical analysis. The research was approved by the Ethics Committee on Research of the Universidad Autónoma de Bucaramanga and HUV. Results: Out of the eighty cases, 53.8% were female and 46.2% were male. 65% were Hispanic and 35% African-American. 22.5% had a history of hematopoietic diseases and 45% were hospitalized for diagnoses included in this category of ICD-10. 79% of women had obstetric history. 18.75% were transfused previously. 36% of the cases had a CceeK- phenotype. 31.25% had alloantibody Anti-E followed by Anti-K 21.25%. Conclusions: The major alloantibody identified was Anti-E followed by Anti-K. Additionally, the associated alloantibody could not be identified in a large group mainly due to antibody mixture. Also, most cases correspond to young adults and adults. In the clinical characteristics of the sample a discretere presentation of congenital hemoglobinopathies was observed and most were not previously polytransfused. [Pérez JA, Cortés A. Characterization of Red Blood Cells Alloimmunization at Hospital Universitario del Valle between 2011 and 2013. MedUNAB 2014; 17(2):66-80].

Introdução: As necessidades nacionais de sangue estão parcialmente cobertas no entanto, vale ressaltar, o uso de sangue envolve a detecção e identificação de anticorpos inesperados nos receptores dos componentes eritrocitários. Objetivo: Caracterizar demograficamente e clinicamente os casos de aloimunização eritrocitária no serviço de transfusão sanguínea do Hospital Universitário do Valle (HUV Cali, Valle del Cauca, Colômbia) no período de 2011 e 2013. Método: Foi desenhado estudo transversal com os casos de aloimunização eritrocitária transfundidos no serviço de transfusão sanguínea do HUV no período de 1 de Agosto de 2011 a 31 de julho de 2013. Os casos foram incluídos por meio de uma amostragem aleatória sistemática, tendo sido utilizado o programa Epi-Info para Windows para a entrada de dados e análise dos mesmos. Estudo foi aprovado pelo comitê de ética. Resultados: Foram identificados e incluídos 80 casos, sendo 53.8% do sexo feminino e 46.2% do sexo masculino.65% eram de hispânicos mestiços e 35% afrodescendentes. 22.5% tinham histórico de doenças hematopoéticas e 45% estiveram hospitalizados por diagnósticos incluídos nesta categoria da CIE-10. 79% das mulheres tinham história obstétrica. 18.75% apresentavam transfusãoprévia. 36% dos casos tinham um fenótipo CceeK. 31.25% tinha aloanticorpo anti-E, enquanto 21.25% apresentavam anti-K. Conclusões: O principal aloanticorpo identificado foi o Anti-E seguido pelo Anti-K. Houve um grupo importante de pacientes onde não se pode ser identificar aloanticorpo associado devido, principalmente, à mistura de anticorpo. A maioria dos casos corresponde a adulto-jovens e adultos. Em relação às características clínicas da amostra foi observada uma pequena participação de hemoglobinopatias congênitas e maioria não apresentou politransfusão prévia. [Pérez JA, Cortés A. Caracterização de aloimunização eritrocitária no Hospital Universitário do Valle no período de 2011 a 2013. MedUNAB 2014; 17 (2): 66-80].

Bloqueo AV completo congénito: Revisión y presentación de un caso / Congenital complete av block: Review and case report

El bloqueo auriculoventricular es un retardo o interrupción del impulso eléctrico proveniente del nodo sinusal a nivel del nódulo auriculoventricular. Es congénito en uno de cada 20,000-25,000 nacidos vivos. Secundario a desarrollo embrionario anormal del nodo auriculoventricular asociado a anomalías cardiacas estructurales o por isoinmunización materna con anticuerpos que dan daño inmunológico irreversible del tejido cardiaco del feto, por inflamación y fibrosis. Los factores de mal pronóstico son: coexistencia con malformaciones cardiovasculares, insuficiencia cardiaca, frecuencia ventricular menor de 50 por min, bradicardia durante el sueño menos de 30 por min, marcapaso bajo o cambiante, QT prolongado. En asintomáticos, se recomienda seguimiento con monitoreo y ecocardiografía. Las indicaciones de marcapasos permanente son: ritmo de escape con complejos anchos, ectopia y disfunción ventricular, QT largo, cardiomegalia y auriculomegalia derecha.

The atrioventricular block is a delay or interruption of the electrical impulse from the sinusal node, to level of the auriculoventricular nodule is a congenital (BAVC), in one of every 20,000-25,000 born alive. Secondary to an abnormal embryonic development of the node AV, associated with structural cardiac abnormalities or for maternal is immunization with antibodies that cause immunological irreversible damage in the fetal heart tissue, by inflammation and subsequent fibrosis. The factors of worst prognosis are: Coexistence with cardiovascular malformations, heart failure, ventricular frequency below 50 per minute, bradycardia less than 30 per minute during sleep, pacemaker under or changing, long QT. In asymptomatic patient, it is recommended monitoring and follow-up with echocardiography. Indications for permanent pacemaker are: escape rhythm with wide complex, ectopy and ventricular dysfunction, long QT, cardiomegaly and right atrial dilatation.

Resultado neonatal e infantil de niños con y sin transfusión intrauterina por isoinmunización Rh durante el embarazo / Neonatal outcome of children with and without intrauterine transfusion for Rh isoimmunization during pregnancy

Objetivo: Comparar la morbilidad neonatal y a seis meses de vida de hijos de pacientes con isoinmunización Rh que recibieron al menos una transfusión intrauterina (TIU), con aquellos que no la requirieron. Método: Estudio de caso y control de pacientes con diagnóstico de isoinmunización Rh controladas en la Unidad de Medicina Fetal del Hospital Clínico Universidad de Chile. Se comparó el resultado perinatal y hasta 6 meses de vida de recién nacidos (RN) con TIU (9 casos) y sin TIU (14 casos) entre los años 2004 y 2009. Resultados: Aunque la sobrevida a los 6 meses de los fetos con TIU fue alrededor de un 80 por ciento, solo una muerte puede atribuirse a la severidad de su condición de base. Los RN con TIU nacieron a una menor edad gestacional que los que no requirieron este tratamiento (34,4 +/- 2,2 sem vs. 37,4 +/- 0,6 sem; p=0,003). Al evaluar el manejo neonatal inmediato se observa que el 60 por ciento de los RN isoinmunizados sin TIU requirieron ser hospitalizados y requirieron fototerapia, mientras que todos los RN con antecedente de TIU fueron hospitalizados, recibieron fototerapia y 30 por ciento requirió una exanguineo transfusión. A los 6 meses de vida, 75 por ciento y 20 por ciento de los RN isoinmunizados, con y sin TIU, fueron hospitalizados para una nueva transfusión de GR y/o fototerapia, respectivamente. Conclusión: La isoinmunización Rh es una patología de alto riesgo, pero la terapia intrauterina, en los casos con anemia moderada y severa, permite llegar a edades gestacionales que dan una adecuada sobrevida.

Objective: To compare neonatal and six months of life morbidity of babies affected by Rh isoimmunization during pregnancy that required at least one intrauterine blood transfusion, with babies that did not required that procedure. Methods: Case control study of patients with diagnosis of Rh isoimmunization under control in the Fetal Medicine Unit at the University of Chile Hospital. Perinatal and until 6 months of life outcomes of isoimmunized newborns (NB) with (9 cases) and without intrauterine transfusion (IUT) (14 cases) between years 2004 and 2009 were compared. Results: Although six months of life survival of IUT babies was about 80 percent only one death was related to the severity of isoimmunization. Isoimmunized babies with IUT were delivered at a lower gestational age than those without IUT (34.4 +/- 2.2 vs. 37.4 +/- 0.6 weeks; p=0.003). At the immediate neonatal period only 60 percent of isoimmunized babies without IUT required hospitalization and phototherapy, in contrast to IUT babies where all of them were hospitalized and required phototherapy, and 30 percent required exchange transfusion. Until six months of life, 75 percent and 20 percent of NB with and without IUT required another hospitalization for a new transfusion and/or phototherapy respectively. Conclusion: Rh isoimmunization is a high risk disease, but intrauterine therapy in cases with moderate and severe fetal anemia increases gestational age at delivery with good survival rates.

Sensitization to Multiple Rh Antigens by Transfusion of Random Donor Platelet Concentrates in a -D- Phenotype Patient

The -D- phenotype is a rare Rh phenotype that strongly expresses D antigen without C, c, E, or e antigens. In -D- phenotype individuals, anti-Rh17 (Hro) is commonly found if there is a history of pregnancy or transfusion with red blood cells (RBCs) that express C, c, E, or e antigens. We report the first case of a -D- phenotype patient with multiple Rh antibodies including anti-Rh17 who had a history of two occasions of transfusion with eight random donor platelet concentrates two and six years ago. We found that a trivial amount of RBCs in the platelet components was able to trigger sensitization to RBC antigens, especially the highly immunogenic and clinically significant Rh antigens, including C, c, E, e or CcEe polypeptides. To avoid unnecessary sensitization and to minimize the risk of hemolytic transfusion reactions in patients with this rare Rh phenotype, a modified strategy for pretransfusion screenings needs to be discussed in the field of transfusion medicine.

Genotipagem RhD fetal não invasiva no acompanhamento de gestantes RhD negativo / Non invasive Fetal RHD Genotyping in management of pregnant RhD negative women

O acompanhamento de gestantes de fenótipo RhD negativo é baseado na premissa de que seus fetos podem estar em risco de desenvolver a doença hemolítica perinatal (DHPN) ou eritroblastose fetal, trazendo sérios riscos ao feto em decorrência de hemólise, com consequente anemia, hidropsia e, por vezes, óbito intrauterino. Procedimentos invasivos como amniocentese ou cordocentese podem ser utilizados para se inferir o fenótipo RhD fetal, entretanto, oferecem riscos ao feto e à gestante. Nos últimos anos, o conhecimento sobre a genética dos grupos sanguíneos e o desenvolvimento de técnicas de biologia molecular tem permitido a inferência de fenótipos de grupos sanguíneos a partir da detecção do material genômico. Inicialmente, a genotipagem do DNA fetal para o gene RhD era feita a partir de amostras de amniócitos ou de vilosidades coriônicas. No entanto, por tratar-se de testes invasivos, traziam risco ao feto e à gestante. A possibilidade de se obter DNA fetal a partir do plasma materno foi um grande avanço na prática clínica, por ser um procedimento não invasivo e, portanto, isento de risco. Esta revisão apresenta os princípios da técnica e os resultados de diferentes protocolos para genotipagem RhD fetal (publicados ao longo dos anos) e qual o seu propósito no acompanhamento das gestantes RhD negativo

The RhD negative pregnant women management has been based on the fact that their fetuses may be at risk of developing hemolytic diseases (DHPN) or erythroblastosis fetalis. This condition may bring serious risks to the fetus due to hemolysis, with consequent anemia and hydrops and sometimes, intrauterine death. Invasive procedures such as amniocentesis or cordocentesis may be performed to assess the fetal RhD phenotype, however, it offers risks to both fetus and pregnant woman. In recent years, the knowledge about the genetics of blood groups and the development of molecular biology techniques has allowed the inference of blood group phenotypes by the detection of genomic material. Initially, the fetal DNA genotyping for the RHD gene was performed from amniocytes or chorionic villi samples. Unfortunately, these invasive tests could bring risk to the fetus and the pregnant woman. However, the possibility of obtaining fetal DNA from maternal plasma has been a major advance in clinical practice, as being a non-invasive procedure and therefore not providing any risks. This review presents the principles of techniques and results of different protocols for fetal RHD genotyping (published over the years) and its goal on the management of RhD negative pregnant women

Enfermedad hemolítica perinatal: manejo de la embarazada RhD negativo / Perinatal hemolytic disease: management of RhD immunization in pregnancy

En solo 50 años la enfermedad hemolítica perinatal por isoinmunización anti D pasó de ser una enfermedad sin etiología conocida, incurable y no prevenible, a la situación actual en que por las técnicas de prevención, diagnóstico oportuno y tratamiento especializado tiene baja incidencia y altas expectativas de sobrevida, incluso en los casos más severos. Se describe la historia, las técnicas de prevención, diagnóstico, manejo y tratamiento de la enfermedad.

In just 50 years the perinatal hemolytic disease due to RhD isoimmunization went from being a disease without known etiology, untreatable and not preventable to the current situation in which the prevention techniques, opportune diagnosis and specialized treatment has low its incidence and has an expected high survival even in the more severe cases. This article describes the history, prevention techniques, diagnosis, management and treatment of the disease.