Prevención de enfermedad hemolítica perinatal severa con inmunoglobulina intravenosa en paciente altamente sensibilizada / Prevention of severe perinatal hemolytic disease with intravenous immunoglobulin in a highly sensitized patient

RESUMEN La enfermedad hemolítica perinatal es infrecuente hoy por la prevención que de ella se hace. Sin embargo, existen casos de madres altamente sensibilizadas que desean tener un hijo, lo que obliga a que ese embarazo deseado sea controlado de manera especial y sometido a procedimientos invasivos no exentos de morbimortalidad fetal. El uso prenatal de inmunoglobulina humana en la madre puede representar una alternativa terapéutica. Se presenta un caso en que su uso impidió el desarrollo de enfermedad intrauterina y favoreció la buena evolución neonatal a pesar de que el pronóstico inicial era muy adverso.

ABSTRACT Perinatal Hemolytic Disease is uncommon today due to its prevention. However, there are cases of highly sensitized mothers who wish to have a child, that forces this desired pregnancy to be controlled in a special way and be subjected to invasive procedures not exempt from fetal morbidity and mortality. Prenatal use of human inmunoglobulin in the mother may represent a therapeutic alternative. We present a case in which its use prevented the development of intrauterine disease and favored a good neonatal evolution despite the fact that the initial prognosis was very adverse.

Atualizações na profilaxia da isoimunização Rh / Updates in the prophylaxis of the Rh isoimmunization

O conhecimento da isoimunização Rh e das bases moleculares do gene RHD e de suas variantes cresceu muito nos últimos anos. Esse crescimento permitiu a introdução de ferramentas realmente úteis no acompanhamento a gestantes isoimunizadas ou em risco de desenvolver a doença hemolítica perinatal (DHPN). A introdução da imunoprofilaxia RhD, por volta dos anos 1960, propiciou uma significativa redução na incidência de aloimunização materna por anti-D. Essa redução torna-se ainda mais significante quando há a associação da profilaxia pós-natal à antenatal, entretanto, seu uso ainda não é amplamente difundido no Brasil e sua eficiência está diretamente relacionada à dose correta, que vai depender da idade gestacional e da quantidade de hemorragia feto-materna (HFM). Sabe-se ainda que a imunoglobulina anti-D policlonal, por ser de origem humana, não é isenta de riscos à gestante ou ao concepto. Dada essa limitação, anticorpos monoclonais têm sido produzidos e avaliados a fim de substituir o anti-D policlonal. Todavia, até o momento, o sucesso dessa nova tecnologia tem sido apenas parcial. Como uma importante alternativa, entretanto, tem sido estudada a habilidade de indução de tolerância à proteína RhD, em ratos transgênicos, a partir de peptídios sintéticos

The knowledge of the Rh isoimmunization and the molecular bases of RHD gene and its variants has grown in recent years. This growth allowed the introduction of useful tools in monitoring pregnant women with alloimmunization or at risk of developing hemolytic disease of the newborn (HDN). The introduction of RhD immunoprophylaxis, in the 1960 years, provided a significant reduction in the incidence of maternal alloimmunization by anti-D. This reduction becomes even more significant when associated with antenatal prophylaxis, however, its use is not yet widespread in Brazil and its efficiency is directly related to the correct dose that will depends on the gestational age and the fetomaternal hemorrhage (FMH) quantity. It is also known that anti-D polyclonal, to be of human origin, is not without risk to the mother or the fetus. Given this limitation, monoclonal antibodies have been produced and evaluated in order to replace the polyclonal anti-D. Nevertheless, so far the success of this new technology has been only partial. As an important alternative, however, the ability to induce tolerance to the RhD protein in transgenic mice from synthetic peptides has been studied

Score Delphos 1: estimación del grado de afectación fetal en enfermedad hemolítica del recién nacido / Delphos I Score: estimation of the degree of fetal affectation in haemolytic disease of the newborn

Objetivos: Realizar un modelo de score de riesgo en pacientes sensibilizadas. Predecir el comportamiento futuro e identificar la población con mayor probabilidad de complicaciones feto-neonatales. Métodos: Se realizó un modelo de score de riesgo, DELPHOS l. Se analizaron las fichas inmunohematológicas de 91 pacientes embarazadas sensibilizadas en el período 1999-2008. Se incluyeron: pacientes puérperas, sensibilizadas a anticuerpos anti D solo o asociado a otro productor de enfermedad hemolítica (EH), parto o cesárea con recién nacido en este hospital. Se excluyeron: pacientes embarazadas, sensibilizadas a anticuerpos no productores de EH, pacientes con recién nacido derivado a otro nosocomio. Para su construcción se confeccionó una tabla valorando: antecedentes obstétricos, edad gestacional, titulo, tipo, número de anticuerpos y causas de incremento del título de anticuerpos. Se dio a cada punto citado un puntaje mínimo y máximo. Se procedió al ensayo del mismo comparando la puntuación obtenida con la evolución del feto/neonato en cada caso. Resultados: El 66% de las pacientes consultaron antes de la semana 25 de embarazo presentando score más alto respecto a las que consultaron a las 25 semanas o más. El número de recién nacidos Rh positivos no afectados fue mayor hasta el score 5; a partir de este, aumentó el número y la gravedad de la afectación. Las pacientes sometidas a transfusión intrauterina (TIU) fueron aquellas con score igual o mayor a 6. Por lo tanto el score 6 resultó ser punto de corte a partir del cual se incrementó la afectación feto-neonatal. Conclusión: Un modelo de score permitiría simplificar y mejorar la elección de la conducta a tomar frente a pacientes sensibilizadas.

Objectives: Create a score model to assess risk in sensitized patients. Predict future behaviour and identify the population with higher probability of fetal and neonatal complications. Methods: A risk score model was created, DELPHOS l. The immunohematological record cards of 91 sensitized pregnant patients (1999 through 2008) were surveyed. The following were included: sensitized puerperal patients with anti-D as sole causing antibody or associated to another Haemolytic Disease (HD)-producing antibody, vaginal birth or Caesarean section, with their newborn still in this hospital. The following were excluded: pregnant patients, sensitization by non HD­-producing antibodies, patients with newborn sent to other healthcare facilities. For its construction, a chart was designed evaluating: obstetric medical records, gestational age, titre, type, number of antibodies and causes for antibody increase. A minimum and maximum number of points was assigned to each of the mentioned criteria. A test run was carried out, comparing the obtained number of points with the clinical status of the fetus/newborn in each case. Results: 66% of the patients consulted before 25 weeks pregnancy exhibiting higher scores; as opposed to those that consulted at 25 or more weeks pregnancy. The number of non-affected Rh-positive newborns was higher, up until score 5; from that point on, the number and severeness of affectation increased. The patients to undergo intra-uterine transfusion, were those with score 6 or higher. Therefore score 6 turned out to be the breaking-point starting from which, the fetal/neonatal affectation increased. Conclusion: A score model would allow to simplify and improve the course of action in the management of sensitized patients.

Planned conception in a hyper immunized rhesus-d negative mother by elective plasmapheresis.

Here we report a case of planned pregnancy in a Hyper immunized Rh D negative Banker lady who was interested to have a healthy baby in her fourth Gestation as previous conceptions were ended by intra uterine death (IUDs) due to Rhesus Hemolytic diseases of new born (HDN) which is a condition where the lifespan of the infant's red cells is shortened by the action of specific antibodies derived from the mother by placental transfer. The disease begins in intrauterine life and is therefore correctly described as hemolytic disease of the fetus (HDF) and new born, but the simple term HDN has been used for a long time and can be taken to include hemolytic disease of the fetus (HDF). This hemolytic process takes place in utero and results in marked compensatory overproduction of young nucleated red cells in fetal erythropoietic sites. For this reason the disease also called erythroblastosis foetalis. Elective plasmapheresis done at the Transfusion Medicine Department of BSMMU, Dhaka on her, 800 ml. plasma were extracted in 4 different sessions during her antenatal period. One healthy male baby was delivered by LUCS at 32 weeks of pregnancy; the Baby has to receive 170 ml. O negative fresh Whole Blood as Exchange Transfusion to correct mild hyper bilirubinimia and anemia. Manual plasmapheresis may thus be practiced to all Hyper-immunized carrying mothers to prevent intra uterine death (IUD) in Rhesus D negative carrying mothers.

Alloimmune cytopenia part I hemolytic disease of the fetus and the newborn [HDFN]

One of the most dramatic advances of modern medicine has been the discovery and development of diagnostic methods, treatment and prophylaxis of hemolytic disease of the fetus and the newbom [HDFN]. In a few decades, the field has progressed from a complete lack of understanding of the condition to a detailed grasp and understanding of the molecular and immunological bases of the disease. These advances have in turn culminated in the development of prophylaxis and the near total elimination of its morbidity. In this review, we shall briefly cover the history and progress of developments of this condition and presents the new concepts in the classification and nomenclature of alloimmune cytopenia of pregnancy. We will also provide a short account on advances in the pathophysiology, treatment and prevention of this condition. A review of developments in management will be discussed together with highlights of health care issues of women with alloimmune cytopenia

Evaluación de los anticuerpos monoclonales anti-D para la tipificación del sistema Rh(D) / Assessment of antigen-D monoclonal antibodies in the typification of Rh(D) system

El Ag Rh (D) presenta gran variabilidad en su expresión fenotípica; por esta razón los reactivos, así como las técnicas empleadas para realizar la hemotipificación Rh, varían de acuerdo con su habilidad para detectar estas variantes. En el presente trabajo se realizó la evaluación de la capacidad de los anticuerpos monoclonales (AcMo), anti-Rh(D) de clases IgG e IgM para ser utilizados en la tipificación de grupo sanguíneo Rh(D) con respecto a las características inmunohematologícas de título, puntuación, presencia de Acs contaminantes, reacción con fenotipos -d débiles y concentración. La mayoría de los AcMo analizados resultaron adecuados para ser utilizados con estos fines. Se determinó que la relación título/concentración es el parámetro adecuado como para predecir la capacidad que tienen estos anticuerpos de clase IgG en relación con la detección del fenotipo D débil, mientras que en el caso de los AcMo anti-Rh(D) de clase IgM la determinación más importante resultó ser el título. Todos los AcMo analizados se enfrentaron con diferentes fenotipos de células Rh(D) negativo con los siguientes fenotipos: Ccddee (r'r), ccddEe (r"r), A ccddee, B ccddee y O ccddee (rr); en ningún caso se observó hemaglutinación, lo que evidenció la ausencia de anticuerpos contaminantes. Se estudió la influencia del epítope en la calidad de este reactivo; los AcMo anti Rh(D) de clase IgG específicos para epítopes discontinuos no detectan la mayoría de los fenotipos D débiles. Los resultados obtenidos demuestran la necesidad que aún existe de continuar el estudio de los aspectos que influyen en la especificidad de los anticuerpos anti-D por el Ag D en el eritrocito.