RESUMEN
BACKGROUND AND OBJECTIVES: Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in â¼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. METHODS: We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. RESULTS: A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. CONCLUSIONS: Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia.
Asunto(s)
Eritroblastosis Fetal , Isoanticuerpos , Isoinmunización Rh , Humanos , Femenino , Embarazo , Recién Nacido , Isoanticuerpos/inmunología , Isoanticuerpos/sangre , Isoinmunización Rh/inmunología , Isoinmunización Rh/epidemiología , Eritroblastosis Fetal/inmunología , Eritroblastosis Fetal/epidemiología , Eritroblastosis Fetal/diagnóstico , Resultado del Embarazo/epidemiología , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Masculino , Globulina Inmune rho(D)/inmunología , Adulto , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVES: To evaluate the severity of haemolytic disease of the foetus and newborn (HDFN) in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease. MATERIALS AND METHODS: Nationwide prospective cohort study, including all pregnant women with RhD antibodies. All women with at least two pregnancies with RhD antibodies and RhD-positive foetuses were selected. The main outcome measure was the severity of HDFN in the first and subsequent pregnancy at risk. A subgroup analysis was performed for the group of women where RhD antibodies developed after giving birth to an RhD-positive child and thus after receiving anti-D at least twice (group A) or during the first pregnancy at risk for immunization (group B). RESULTS: Sixty-two RhD immunized women with a total of 150 RhD-positive children were included. The severity of HDFN increased for the whole group significantly in the subsequent pregnancy (p < 0.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, after giving birth to an RhD-positive child (group A), severe HDFN in the next pregnancy was uncommon (22%). Especially when no therapy or only non-intensive phototherapy was indicated during the first immunized pregnancy (6%) or if the antibody-dependent cell-mediated cytotoxicity result remained <10%. Contrarily, women with a negative first trimester screening and RhD antibodies detected later during the first pregnancy of an RhD-positive child (group B), often before they had ever received anti-D prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%). CONCLUSION: RhD-mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of an RhD-positive child are at highest risk of severe disease in the next pregnancy.
Asunto(s)
Eritroblastosis Fetal , Sistema del Grupo Sanguíneo Rh-Hr , Humanos , Femenino , Embarazo , Adulto , Eritroblastosis Fetal/prevención & control , Eritroblastosis Fetal/inmunología , Estudios Prospectivos , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Globulina Inmune rho(D) , Índice de Severidad de la Enfermedad , Recién Nacido , Isoinmunización Rh/prevención & control , Estudios de Cohortes , Isoanticuerpos/sangre , InmunizaciónRESUMEN
Since publication of the original Immunohematology review of the Kidd blood group system in 2015 (Hamilton JR. Kidd blood group system: a review. Immunohematology 2015;31:29-34), knowledge has mushroomed pertaining to gene structure, alleles causing variant and null phenotypes, clinical significance in renal transplant and hemolytic disease of the fetus and newborn, and physiologic functions of urea transporters in non-renal tissues. This review will detail much of this new information.
Asunto(s)
Sistema del Grupo Sanguíneo de Kidd , Trasplante de Riñón , Humanos , Sistema del Grupo Sanguíneo de Kidd/genética , Sistema del Grupo Sanguíneo de Kidd/inmunología , Transportadores de Urea , Eritroblastosis Fetal/genética , Eritroblastosis Fetal/inmunología , Eritroblastosis Fetal/sangre , Recién Nacido , Proteínas de Transporte de Membrana/genética , Alelos , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/inmunologíaRESUMEN
In pregnancy, D- pregnant women may be at risk of becoming immunized against D when carrying a D+ fetus, which may eventually lead to hemolytic disease of the fetus and newborn. Administrating antenatal and postnatal anti-D immunoglobulin prophylaxis decreases the risk of immunization substantially. Noninvasive fetal RHD genotyping, based on testing cell-free DNA extracted from maternal plasma, offers a reliable tool to predict the fetal RhD phenotype during pregnancy. Used as a screening program, antenatal RHD screening can guide the administration of antenatal prophylaxis in non-immunized D- pregnant women so that unnecessary prophylaxis is avoided in those women who carry a D- fetus. In Europe, antenatal RHD screening programs have been running since 2009, demonstrating high test accuracies and program feasibility. In this review, an overview is provided of current state-of-the-art antenatal RHD screening, which includes discussions on the rationale for its implementation, methodology, detection strategies, and test performance. The performance of antenatal RHD screening in a routine setting is characterized by high accuracy, with a high diagnostic sensitivity of ≥99.9 percent. The result of using antenatal RHD screening is that 97-99 percent of the women who carry a D- fetus avoid unnecessary prophylaxis. As such, this activity contributes to avoiding unnecessary treatment and saves valuable anti-D immunoglobulin, which has a shortage worldwide. The main challenges for a reliable noninvasive fetal RHD genotyping assay are low cell-free DNA levels, the genetics of the Rh blood group system, and choosing an appropriate detection strategy for an admixed population. In many parts of the world, however, the main challenge is to improve the basic care for D- pregnant women.
Asunto(s)
Sistema del Grupo Sanguíneo Rh-Hr , Globulina Inmune rho(D) , Humanos , Embarazo , Femenino , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Sistema del Grupo Sanguíneo Rh-Hr/genética , Sistema del Grupo Sanguíneo Rh-Hr/sangre , Globulina Inmune rho(D)/uso terapéutico , Globulina Inmune rho(D)/sangre , Diagnóstico Prenatal/métodos , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Eritroblastosis Fetal/prevención & control , Eritroblastosis Fetal/diagnóstico , Eritroblastosis Fetal/sangre , Eritroblastosis Fetal/inmunologíaRESUMEN
BACKGROUND: We report an obstetric case involving an RhD-positive woman who had developed a red blood cell (RBC) antibody that was not detected until after delivery of a newborn, who presented with a positive direct antiglobulin test result. Immunohematology studies suggested that the maternal antibody was directed against a low-prevalence antigen on the paternal and newborn RBCs. RESULTS: Comprehensive blood group profiling by targeted exome sequencing revealed a novel nonsynonymous single nucleotide variant (SNV) RHCE c.486C>G (GenBank MZ326705) on the RHCE*Ce allele, for both the father and newborn. A subsequent genomic-based study to profile blood groups in an Indigenous Australian population revealed the same SNV in 2 of 247 individuals. Serology testing showed that the maternal antibody reacted specifically with RBCs from these two individuals. DISCUSSION: The maternal antibody was directed against a novel antigen in the Rh blood group system arising from an RHCE c.486C>G variant on the RHCE*Ce allele linked to RHD*01. The variant predicts a p.Asn162Lys change on the RhCE protein and has been registered as the 56th antigen in the Rh system, ISBT RH 004063. CONCLUSION: This antibody was of clinical significance, resulting in a mild to moderate hemolytic disease of the fetus and newborn (HDFN). In the past, the cause of such HDFN cases may have remained unresolved. Genomic sequencing combined with population studies now assists in resolving such cases. Further population studies have potential to inform the need to design population-specific red cell antibody typing panels for antibody screening in the Australian population.
Asunto(s)
Eritroblastosis Fetal , Sistema del Grupo Sanguíneo Rh-Hr , Humanos , Sistema del Grupo Sanguíneo Rh-Hr/genética , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Femenino , Recién Nacido , Eritroblastosis Fetal/genética , Eritroblastosis Fetal/inmunología , Embarazo , Masculino , Adulto , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Alelos , Eritrocitos/inmunología , Polimorfismo de Nucleótido SimpleRESUMEN
ABSTRACT: Hemolytic disease of fetus and newborn (HDFN) is a life-threatening disease mediated by maternal alloimmunization to red blood cell (RBC) antigens. Studies of maternal alloimmunization prevalence in the United States lack national data. This study describes prevalence and trends in alloimmunization in pregnancy in the United States. RBC antibodies (abs) were identified in a large, nationwide, commercial laboratory database from 2010 through 2021. The cohort comprised pregnancies for which the year of laboratory collection and patient's state of residence were available. Data were normalized based on US Centers for Disease Control and Prevention estimates of live births and weighted by year and US Census Division. Cochrane-Armitage tests assessed temporal trends of alloimmunization. Of 9 876 196 pregnancies, 147 262 (1.5%) screened positive for RBC abs, corresponding to an estimated prevalence of 1518 of 100 000 pregnancies. Of identified RBC abs, anti-D comprised 64.1% pregnancies (586/100 000). Prevalence of other high-risk RBC abs for HDFN included anti-K (68/100 000) and anti-c (29/100 000). Incidence of all 3 high-risk abs increased from 2010 to 2021 (all P < .001). Among almost 10 million pregnancies in the United States, comprising an estimated 14.4% of all pregnancies, 1.5% screened positive for RBC abs. Almost three-quarters (679/100 000 [74.3%]) of RBC abs identified were high risk for HDFN. Although prevalence of anti-D is difficult to interpret without the ability to distinguish alloimmunization from passive immunity, it remains problematic in HDFN, ranking second only to anti-K in critical titers. Given the sequelae of HDFN, new initiatives are required to reduce the incidence of alloimmunization in patients of reproductive potential.
Asunto(s)
Eritrocitos , Isoanticuerpos , Humanos , Estados Unidos/epidemiología , Femenino , Embarazo , Eritrocitos/inmunología , Prevalencia , Isoanticuerpos/inmunología , Isoanticuerpos/sangre , Eritroblastosis Fetal/epidemiología , Eritroblastosis Fetal/inmunología , AdultoRESUMEN
BACKGROUND: Anti-s is a rare alloantibody, and the reported cases of hemolytic disease of the fetus and newborn (HDFN) caused by anti-s are limited to non-Asian populations. METHODS: Here, we report the case of a Chinese woman with a history of multiple pregnancies who developed an alloantibody with anti-s specificity. RESULTS: Her newborn developed HDFN caused by anti-s but the clinical symptoms were not serious. After supportive treatment and bilirubin light phototherapy, the baby was discharged with a good prognosis. CONCLUSIONS: This is the first reported case of anti-s-induced HDFN in a Chinese patient, highlighting the need for further research in the Asian population.
Asunto(s)
Antígenos de Grupos Sanguíneos , Pueblos del Este de Asia , Eritroblastosis Fetal , Isoanticuerpos , Femenino , Humanos , Recién Nacido , Embarazo , Eritroblastosis Fetal/diagnóstico , Eritroblastosis Fetal/etiología , Eritroblastosis Fetal/inmunología , Eritroblastosis Fetal/terapia , Feto/inmunología , Hemólisis/inmunología , Isoanticuerpos/inmunología , Antígenos de Grupos Sanguíneos/inmunología , FototerapiaRESUMEN
The D antigen is one of the most immunogenic and clinically significant antigens of the Rh blood group system due to its various genotypes that encode for more than 450 different variants. Accurate RhD typing and D variant identification is crucial specially in prenatal screening during pregnancy. Women with RhD -ve phenotype are eligible to Rh immune globulin (RhIG) prophylaxis for the prevention of anti-D alloimmunization and hemolytic disease of the fetus and newborn (HDFN). However, there are some women who possess RhD variant alleles, who are mistakenly grouped as RhD positive and considered not eligible for RhIG prophylaxis, putting them at risk of anti-D alloimmunization and consequently leading to HDFN during subsequent pregnancies. Here, we describe two cases of RhD variants DAU2/DAU6 and Weak D type 4.1 in obstetric patients who were grouped as RhD +ve with negative antibody screening during routine serologic testing. Weak/Partial D molecular analysis using genomic DNA Red Cell Genotyping (RCG) revealed that both patients had RhD variants, one of which DAU2/DAU6 allele associated with anti-D alloimmunization. According to routine testing neither patients received RhIG or transfusion. In this case report we document to our knowledge the first reported cases of RhD variants among pregnant women in Saudi Arabia.
Asunto(s)
Embarazo , Sistema del Grupo Sanguíneo Rh-Hr , Femenino , Humanos , Embarazo/genética , Embarazo/inmunología , Alelos , Eritroblastosis Fetal/inmunología , Eritroblastosis Fetal/prevención & control , Eritroblastosis Fetal/terapia , Genotipo , Fenotipo , Sistema del Grupo Sanguíneo Rh-Hr/genética , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Globulina Inmune rho(D)/uso terapéutico , Arabia SauditaRESUMEN
Maternal alloantibodies directed against fetal red blood cell (RBC) antigens may cause potentially life-threatening haemolytic disease of the fetus and newborn (HDFN). Dutch transfusion guidelines therefore prescribe preventive cEK matching for all (pre-)fertile females. To quantify the impact of cEK matching, we compared overall and antigen-specific cumulative RBC alloimmunisation incidences in females and males aged <45 years. Among a multicentre cohort comprised of patients who received their first and subsequent RBC unit between 2005 and 2019, first-formed RBC alloantibodies were detected in 47 of 2998 (1·6%) females and 49 of 2507 (2·0%) males. Comparing females and males, overall alloimmunisation incidences were comparable (3·1% [95% confidence interval (CI) 2·1-4·4] versus 3·5% (95% CI 2·4-4·9, P = 0·853) after 10 units transfused). However, cEK alloimmunisation incidences were significantly lower among females (0·6% (95% CI 0·3-1.5) versus 2·2% (95% CI 1·5-3·4, P = 0·001) after 10 units transfused). Yet, despite cEK-matching guidelines being in effect, 6·5%, 3·6% and 0·2% of all RBC units remained mismatched for c, E or K antigens respectively. Most of these mismatches were almost always due to emergency settings. Even though cEK alloimmunisation was not prevented completely, implementation of cEK matching resulted in an alloantigen-exposure risk reduction of up to 98%.
Asunto(s)
Incompatibilidad de Grupos Sanguíneos/genética , Tipificación y Pruebas Cruzadas Sanguíneas , Eritroblastosis Fetal/etiología , Eritrocitos/inmunología , Isoanticuerpos/biosíntesis , Sistema del Grupo Sanguíneo de Kell/inmunología , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Reacción a la Transfusión/epidemiología , Adulto , Eritroblastosis Fetal/genética , Eritroblastosis Fetal/inmunología , Femenino , Humanos , Incidencia , Isoanticuerpos/inmunología , Sistema del Grupo Sanguíneo de Kell/genética , Masculino , Sistema del Grupo Sanguíneo Rh-Hr/genética , Adulto JovenRESUMEN
BACKGROUND: The anti-M antibody can lead to hemolytic disease of the fetus and newborn (HDFN) and adverse fetal outcomes, especially in the Asian population. However, fetal erythropoiesis resulting from M alloimmunization needs further investigation. STUDY DESIGN AND METHODS: We analyzed erythropoiesis in eight fetuses with M alloimmunization and compared them with the fetuses affected by anti-D. They were matched as pairs according to the gestational age of diagnosis and the hematocrit before treatment. Paired t-tests or paired Wilcoxon rank-sum tests were conducted to compare the difference in the cord blood indexes. Pearson correlation analysis was used to evaluate the correlativity between hematocrit and the reticulocyte percentage in the two groups. RESULTS: The fetuses in the MN group had lower reticulocyte count and percentage than those in the RhD group (p < .05). All of the fetal reticulocyte production indexes (RPIs) in the MN group were less than 2, indicating an inadequate hemopoietic response to anemia, while the majority of the RPIs in the RhD group (85.7%) were significantly higher (p = .003), with 6 cases greater than 2.5. Hematocrit was negatively correlated with reticulocyte percentage (y = 54.7-171.7x, r2 = 0.825, p = .005) in the RhD group, while no significant correlation was found in the MN group. No difference in the number of IUT, interval, or the fetal outcome was found between the two groups. CONCLUSION: Fetal reticulocytopenia provided direct evidence of an inadequate hemopoietic response in HDFN due to anti-M, leading to hyporegenerative anemia. Once the IgG component of anti-M is detected, close monitoring should be considered.
Asunto(s)
Anemia/inmunología , Eritroblastosis Fetal/inmunología , Feto/inmunología , Inmunoglobulina M/inmunología , Isoanticuerpos/inmunología , Adulto , Anemia/etiología , Anemia/fisiopatología , Anemia/terapia , Transfusión de Sangre Intrauterina , Eritroblastosis Fetal/fisiopatología , Eritroblastosis Fetal/terapia , Eritropoyesis , Femenino , Feto/fisiopatología , Humanos , Recién Nacido , Masculino , Embarazo , Reticulocitosis , Globulina Inmune rho(D)/inmunología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Red blood cell alloimmunization is the first cause of fetal and neonatal anemia. Alloimmunizations with anti-PP1Pk or anti-P can cause recurrent miscarriages and hemolytic disease of the fetus and newborn in the 2nd and 3rd trimesters of pregnancy. We report on a pregnant patient immunized with anti-P and a history of recurrent miscarriages. CASE REPORT: This P2k (GLOB:-1; P1PK:-1,3) patient had a first pregnancy marked by a caesarean at 38 weeks of gestation (WG) for non-reassuring fetal heart rate. Then, she had three early spontaneous miscarriages. The fifth pregnancy began with a high titer of anti-P at 128. Early initiation of treatment with Intravenous Immunoglobulins (IVIg) and plasma exchanges (PE) starting at 5 WG permitted us to reduce the titer of anti-P below 32. A healthy infant was delivered by caesarean at 38 WG without anemia at birth and no exchange transfusion was required. DISCUSSION AND REVIEW OF THE LITERATURE: The P and Pk antigens are expressed on placental, trophoblastic, and embryonic cells. This explains why P1k (GLOB:-1; P1PK:1,3), P2k (GLOB:-1; P1PK:-1,3), or Tj(a-)/p (GLOB:-1; P1PK:-1,-3) patients are prone to recurrent abortions in the first trimester of pregnancy. A literature review demonstrated 87% (68/78) of miscarriages in p patients. However, publication biases are possible with the most severe cases being reported. CONCLUSION: Immunizations to P and PP1Pk antigens differ from others in their physiopathology and precocity. The association of PE and IVIg seems to be an effective treatment in the management of anti-PP1Pk or anti-P fetomaternal incompatibilities.
Asunto(s)
Aborto Habitual/sangre , Isoanticuerpos/sangre , Sistema del Grupo Sanguíneo P/sangre , Aborto Habitual/inmunología , Adulto , Eritroblastosis Fetal/sangre , Eritroblastosis Fetal/inmunología , Femenino , Humanos , Isoanticuerpos/inmunología , N-Acetilgalactosaminiltransferasas/sangre , N-Acetilgalactosaminiltransferasas/inmunología , Sistema del Grupo Sanguíneo P/inmunología , EmbarazoAsunto(s)
Formación de Anticuerpos/inmunología , Antígenos/inmunología , Eritroblastosis Fetal/inmunología , Tolerancia Inmunológica/inmunología , Reacciones Antígeno-Anticuerpo/inmunología , Reacciones Antígeno-Anticuerpo/fisiología , Eritrocitos/enzimología , Eritrocitos/inmunología , Feto/inmunología , Humanos , Terapia de Inmunosupresión/efectos adversos , Recién Nacido , Fagocitosis/inmunologíaRESUMEN
BACKGROUND: We hypothesized that variability in practice exists for newborn immunohematology testing due to lack of consensus guidelines. We report the results of a survey assessing that variability at hospitals in the United States and Canada. STUDY DESIGN AND METHODS: An AABB Pediatric Subsection working party developed and validated a survey of newborn immunohematology testing practice. The survey was sent electronically to transfusion service leadership at teaching institutions. RESULTS: The response rate was 67% (61/91); 56 surveys meeting inclusion criteria were analyzed. Approximately 90% (50/56) were from birth hospitals and 16.1% (9/56) were from pediatric hospitals. Newborn immunohematology testing is ordered as a panel by 66.0% (33/50) of birth hospitals. ABO group and DAT is mandated before discharge in 14/56 (25.0%) and 13/56 (23.2%), respectively. About 76.8% (43/56) selectively perform a DAT according to blood blank or clinical parameters. The most common DAT practices include anti-IgG only testing by 73.2% (41/56) and use of umbilical cord specimen type by 67.9% (38/56). A positive DAT is a critical value for 26.8% (15/56) and followed with eluate testing when a maternal antibody screen is positive for 48.2% (27/56). In the setting of a non-ABO maternal red cell antibody, 55.4% (31/56), phenotype neonatal red cells when the DAT is positive. Group O RBC are transfused irrespective of the DAT result for 82.1%, (46/56). CONCLUSION: There is variability in newborn immunohematology testing and transfusion practice and potential overutilization of the DAT. Evidence-based consensus guidelines should be developed to standardize practice and to improve safety.
Asunto(s)
Prueba de Coombs/estadística & datos numéricos , Eritroblastosis Fetal/inmunología , Recién Nacido/inmunología , Medicina Transfusional/normas , Sistema del Grupo Sanguíneo ABO/inmunología , Anticuerpos Antiidiotipos/análisis , Bilirrubina/análisis , Canadá/epidemiología , Prueba de Coombs/normas , Eritroblastosis Fetal/diagnóstico , Eritroblastosis Fetal/epidemiología , Eritrocitos/inmunología , Sangre Fetal/inmunología , Sangre Fetal/metabolismo , Humanos , Hiperbilirrubinemia/sangre , Hiperbilirrubinemia/diagnóstico , Lactante , Recién Nacido/sangre , Guías de Práctica Clínica como Asunto/normas , Prevalencia , Estudios Retrospectivos , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) attributable to anti-M is rare, although case reports implicate anti-M in varying severities of HDFN, including fetal hydrops and intrauterine death. CASE DESCRIPTION: We describe the case of a newborn with HDFN associated with an atypical immunoglobulin (Ig) G anti-M that reacted best at cold temperatures. The maternal antibody detected in pregnancy was not reactive at 37°C, and a direct antiglobulin test (DAT) on red blood cells (RBCs) from the newborn was negative, suggesting an anti-M that should not have been clinically relevant. However, the infant developed hyperbilirubinemia (bilirubin level, 17.6 mg/dL), hemolytic anemia (hemoglobin nadir, 5.5 g/dL), and reticulocytopenia. Laboratory testing demonstrated the presence of an IgG anti-M in maternal and neonatal samples reacting best at 4°C. This passively acquired IgG anti-M provoked hemolytic anemia in the infant and likely suppressed erythropoiesis, resulting in reticulocytopenia with prolonged anemia. He was treated for IgG anti-M HDFN with 10 intravenous Ig infusions and 10 days of oral prednisone followed by a taper. He required seven transfusions with M- RBCs. His hemoglobin level normalized at 3 months of age. Follow-up at 2 years revealed no hematologic or neuro-developmental concerns. CONCLUSION: To our knowledge, this is the second report of HDFN attributable to an IgG anti-M reacting preferentially at cold temperature with no 37°C reactivity. Clinically relevant IgG anti-M may elude standard testing. Early recognition and testing for cold-reacting IgG anti-M should be considered for newborns with hemolysis, a negative DAT, and prolonged anemia.
Asunto(s)
Anemia Hemolítica/inmunología , Eritroblastosis Fetal/diagnóstico , Eritroblastosis Fetal/inmunología , Inmunoglobulina G/sangre , Anemia Hemolítica/complicaciones , Anemia Hemolítica/tratamiento farmacológico , Anemia Hemolítica/etiología , Transfusión Sanguínea , Frío , Prueba de Coombs , Eritroblastosis Fetal/tratamiento farmacológico , Eritroblastosis Fetal/etiología , Eritrocitos/inmunología , Eritropoyesis/inmunología , Femenino , Hemoglobinas/metabolismo , Humanos , Recién Nacido , Masculino , EmbarazoRESUMEN
INTRODUCTION: Antenatal antibody screening in India is focused on the detection of anti-D in RhD-negative mothers. HDFN outcome can also be affected by the presence of antibodies other than anti-D. We planned this study to find the impact of 'anti-D in combination with additional antibodies' on the development and severity of HDFN compared with 'anti-D alone'. METHODS: This is a retrospective study performed at a referral center in northern India from October 2015 to March 2018. Antibody screening was performed on women with complicated obstetric history. Women with anti-D antibody were included in the study and categorized on the basis of presence of additional antibody (anti-D alone or in combination with other antibody). Various clinical, laboratory & interventional parameters were used to define HDFN and severe HDFN. Perinatal outcome was then compared between the two groups. RESULTS: A total of 176 women with anti-D antibody were included in the study. Of these, 136 cases (77.3%) had anti-D alone while at least one additional antibody was present in 40 (22.7 %) cases. Most common additional antibodies were anti-C, anti-E and anti-c. After excluding 46 women for various reasons, 130 women were left for final analysis. Approximately 57% and 78% of cases were affected by severe HDFN amongst women with anti-D alone and in combination, respectively. Relative risk of developing severe HDFN was 1.7 times higher in women with additional antibody. CONCLUSIONS: Patients with combination antibodies were found to have more severe HDFN compared to the ones with anti-D alone.
Asunto(s)
Eritroblastosis Fetal/inmunología , Eritrocitos/inmunología , Isoanticuerpos/inmunología , Femenino , Humanos , India , Embarazo , Estudios RetrospectivosRESUMEN
BACKGROUND: GP.Mur belongs to the GP(B-A-B) hybrid glycophorin family, which is the most common hybrid glycophorin in Southeast Asia. Antibodies against GP.Mur may cause a clinically significant haemolytic disease of the foetus and newborn (HDFN) although, so far, not many cases have been reported in mainland China. MATERIALS AND METHODS: Two Chinese women with a history of severe hydrops foetalis were seen in our centre. Alloantibody identification and GYP.Mur genotyping analysis were used for prenatal evaluation. Intrauterine transfusion was performed in two pregnancies in case 1. The features of these two women are described and literature-reported cases of HDFN related to antibodies against GP.Mur are summarised. RESULTS: The phenotype of both mothers was Mia- Mur-, while the fathers' was Mia+ Mur+ with a heterozygous GYP.Mur hybrid gene as determined by a high-resolution melting method of genotyping. In case 1, the antibodies against GP.Mur were detected in the mother's serum and the cord blood of two foetuses. Fortunately, the latest foetus was successfully saved after intrauterine transfusion. In case 2, hydrops foetalis occurred in the first two pregnancies, but the risk of HDFN was excluded for the third foetus because of the GP.Mur negative phenotype. The literature review showed that 68.8% (11/16) of the reported cases of HDFN related to antibodies against GP.Mur occurred in the Chinese population, and that 37.5% (6/16) of them were cases of severe HDFN. DISCUSSION: More cases of severe HDFN caused by antibodies against GP.Mur are presumably undetected as GP.Mur cells are not included in the panel of obligatory screening tests in most Southeast Asian countries including mainland China. The high-resolution melting method for GYP.Mur genotyping and zygosity detection is helpful in prenatal management.
Asunto(s)
Glicoforinas/inmunología , Isoanticuerpos/inmunología , Adulto , Tipificación y Pruebas Cruzadas Sanguíneas , Transfusión de Sangre Intrauterina , Eritroblastosis Fetal/genética , Eritroblastosis Fetal/inmunología , Eritroblastosis Fetal/terapia , Femenino , Reordenamiento Génico , Técnicas de Genotipaje , Glicoforinas/genética , Humanos , Recién Nacido , Sistema del Grupo Sanguíneo MNSs/genética , Sistema del Grupo Sanguíneo MNSs/inmunología , EmbarazoRESUMEN
ABO incompatibility has emerged as the premier reason for hemolytic disease of the fetus and newborn (HDFN). It always occurs in the offspring of blood group O mother. We present a rare case that the fetus of group A got HDFN caused by the anti-group A immunoglobulin G from a group B mother. The direct Coombs test of the fetus blood was negative, but the indirect Coombs test on A1 standard blood cells was strong positive (4+). The acid release test of antibody on the membrane of red blood cells to A1 standard blood cells was also strong positive (4+). Bilirubin of the fetus reached the threshold of exchange transfusion, but she just received 4 days' phototherapy and 2.2 g albumin intravenous injection, with no packed blood cells transfusion, because her family refused, and came to a favorable outcome. This case reminds us not to ignore the possibility of HDFN in offspring of mothers with non-O blood group.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Eritroblastosis Fetal/inmunología , Inmunoglobulina G/inmunología , Eritroblastosis Fetal/etiología , Eritroblastosis Fetal/terapia , Eritrocitos/inmunología , Femenino , Humanos , Recién NacidoRESUMEN
BACKGROUND: Hemolysis in fetus/newborns is often caused by maternal antibodies. There are currently no established screening procedures for maternal ABO antibodies harmful to fetus/newborn. We investigated the clinical significance, and predictive value of maternal anti-A/B titer for hyperbilirubinemia in ABO-incompatible newborns. METHODS: We conducted a case-control study of blood group O mothers and their ABO-compatible (O) vs. -incompatible (A/B) newborns receiving phototherapy, and of ABO-incompatible newborns receiving phototherapy vs. no phototherapy. Newborn data and treatment modalities were recorded, and total serum bilirubin and hemoglobin were measured. Maternal anti-A/B immunoglobulin-γ (IgG) titers were measured prenatally and perinatally, and negative and positive predictive values (NPV, PPV) were calculated to assess the risk of developing hyperbilirubinemia requiring phototherapy. RESULTS: We found a significantly higher maternal IgG antibody titer in the case group (p < 0.001). Maternal anti-A/B titers at first trimester had modest predictive values: NPV = 0.82 and PPV = 0.65 for neonatal hyperbilirubinemia; titers at birth improved the predictive values: NPV = 0.93 and PPV = 0.73. Newborn hemoglobin was significantly lower in incompatibles compared to compatibles (p = 0.034). Furthermore, increased anti-A/B IgG production during pregnancy was associated with hyperbilirubinemia and hemolysis in incompatible newborns. CONCLUSIONS: There was a significant association between maternal anti-A/B IgG titer and hyperbilirubinemia requiring treatment. IMPACT: Maternal anti-A/B IgG titer in the first trimester and at birth is predictive of hemolytic disease of the ABO-incompatible newborn. Increased IgG anti-A/B production throughout pregnancy in mothers to ABO-incompatible newborns developing hyperbilirubinemia contrasts a constant or reduced production in mothers to newborns not developing hyperbilirubinemia. Screening tools available in most immunohematology laboratories can identify clinically important IgG anti-A/B. Use of maternal samples taken at birth yielded NPV = 0.93 and PPV = 0.73.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Autoanticuerpos/inmunología , Incompatibilidad de Grupos Sanguíneos/complicaciones , Eritroblastosis Fetal/inmunología , Hiperbilirrubinemia Neonatal/inmunología , Inmunoglobulina G/inmunología , Enfermedades del Recién Nacido , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Hiperbilirrubinemia Neonatal/terapia , Recién Nacido , Masculino , Fototerapia , EmbarazoRESUMEN
Anti-D immunoglobulin prophylaxis reduces the risk of RhD negative women becoming alloimmunised to the RhD antigen and is a major preventative strategy in reducing the burden of haemolytic disease of the fetus and newborn (HDFN). HDFN also arises from other maternal red cell antibodies, with the most clinically significant, after anti-D, being anti-K, anti-c and anti-E. Among the 39 human blood group systems advanced genomic technologies are still revealing novel or rare antigens involved in maternal alloimmunisation. Where clinically significant maternal antibodies are detected in pregnancy, non-invasive prenatal testing (NIPT) of cell-free fetal DNA provides a safe way to assess the fetal blood group antigen status. This provides information as to the risk for HDFN and thus guides management strategies. In many countries, NIPT fetal RHD genotyping as a diagnostic test using real-time PCR has already been integrated into routine clinical care for the management of women with allo-anti-D to assess the risk for HDFN. In addition, screening programs have been established to provide antenatal assessment of the fetal RHD genotype in non-alloimmunised RhD negative pregnant women to target anti-D prophylaxis to those predicted to be carrying an RhD positive baby. Both diagnostic and screening assays exhibit high accuracy (over 99 %). NIPT fetal genotyping for atypical (other than RhD) blood group antigens presents more challenges as most arise from a single nucleotide variant. Recent studies show potential for genomic and digital technologies to provide a personalised medicine approach with NIPT to assess fetal blood group status for women with other (non-D) red cell antibodies to manage the risk for HDFN.
Asunto(s)
Anemia Hemolítica Autoinmune/diagnóstico , Eritroblastosis Fetal/inmunología , Pruebas Genéticas/métodos , Isoanticuerpos/inmunología , Diagnóstico Prenatal/métodos , Anemia Hemolítica Autoinmune/patología , Femenino , Humanos , EmbarazoRESUMEN
Rhesus incompatibility in pregnancy may result in haemolytic disease of the fetus and newborn (HDFN). This review discusses the fetal, neonatal and long-term consequences of HDFN and its management. Untreated, the fetal and neonatal prognosis of HDFN is poor. Provision of intravascular intrauterine transfusion (IUT) in a dedicated referral centre significantly reduces perinatal loss. Early-onset, severe fetal anaemia carries a greater risk of adverse fetal and neonatal outcomes and is less amenable to treatment with IUT. Interventions to prevent and treat severe, early onset disease have been investigated, however evidence from randomised controlled trials is required. Neonatal consequences of Rhesus haemolytic disease include early and late postnatal anaemia, and hyperbilirubinaemia leading to bilirubin-induced neurological dysfunction. Neurodevelopmental impairment and adult cardiovascular disease are long-term complications that have been reported in association with severe fetal anaemia. Strategies to prevent fetal hydrops, and further research into the long-term impacts of fetal anaemia may improve health outcomes for adult survivors of HDFN.