Secondary alloanti-D immunization post transfusion of "Asia type" DEL red blood cells.

BACKGROUND: "Asia type" DEL red blood cells (RBCs) express a very weak D antigen and cannot be detected by routine RhD typing. Thus, it is routinely typed as D-negative (D-) blood group and transfused to D- recipients. Here we described a case of secondary alloanti-D immunization that was associated with transfusion of DEL RBCs to D- recipients and was initially considered as primary alloanti-D immunization. CASE PRESENTATION: A 44-year-old D- woman (G2P2) with adenomyosis and anemia underwent transabdominal hysterectomy. She received four units of D- RBCs before operation. Before transfusion, the alloantibody screening test was negative. Four days after the first transfusion, she needed another RBC transfusion. Unexpectedly, the routine pre-transfusion alloantibody screening test became positive and anti-D (titer, 128-fold) was identified, indicating an alloanti-D immunization. The anti-D developed four days after the first transfusion was unexplained, so alloantibody identification was performed on the sample collected before the first transfusion, and weak anti-D combined with anti-E, which was not detectable during the previous routine pre-transfusion alloantibody screening test with non-enzyme-treated screening cells, was identified using bromelain-treated panel cells. The remaining blood samples of first transfusion in bag tails from two donors were collected for RHD genotyping analysis. One donor was later identified as "Asia type" DEL having RHD* 1227 A/01 N.01 genotype. CONCLUSION: Caution should be applied when we conclude that transfusion of "Asia type" DEL RBCs to true D- recipients could induce primary alloanti-D immunization, especially if the short time interval between transfusion and detection of anti-D is observed.

Practices for RhD alloimmunization prevention: a vignette-based survey of midwives.

INTRODUCTION: Despite the availability guidelines to prevent RhD alloimmunization, severe hemolytic disease of fetus and newborn still occurs in high-income countries. The aim of the study was (1) To assess variations in practices for the prevention of RhD alloimmunization, and (2) to understand midwives' acceptance and appropriation of fetal RhD genotyping. METHODS: Descriptive cross-sectional survey of French midwives from September 2017 through January 2018. Participants were asked to complete an internet-based questionnaire that included three clinical vignettes. They were questioned about their practices concerning early pregnancy visit by RhD-negative women, prevention of RhD alloimmunization in women with second-trimester metrorrhagia, and RhD fetal genotyping. RESULTS: A total of 827 midwives completed the questionnaire. Only 21.1% reported that they practice all the preventive measures recommended in early pregnancy. In a situation at high risk of RhD alloimmunization during pregnancy, 97.2% of midwives would perform immunoprophylaxis. Nearly, all midwives reported providing information about RhD alloimmunization (92.4%) at the beginning of pregnancy, although only 11.3% offered both written and verbal information; at the time of systematic anti-D immunoprophylaxis (28 weeks), 78% provided information, but only 2.7% both verbally and in writing. Finally, only 50.8% of midwives preferred to include RhD fetal genotyping in routine prenatal prophylaxis. DISCUSSION: This study showed significant variations in French midwives' practices to prevent RhD alloimmunization. Better dissemination of guidelines is needed to improve both consistent use of these practices and the quality of information delivered to RhD-negative pregnant women.

Impact of red blood cell alloimmunization on fetal and neonatal outcomes: A single center cohort study.

BACKGROUND: Alloimmunization can impact both the fetus and neonate. STUDY OBJECTIVES: (a) calculate the incidence of clinically significant RBC isoimmunization during pregnancy, (b) review maternal management and neonatal outcomes, (c) assess the value of prenatal and postnatal serological testing in predicting neonatal outcomes. STUDY DESIGN AND METHODS: A retrospective audit of consecutive alloimmunized pregnancies was conducted. Data collected included demographics, clinical outcomes, and laboratory results. Outcomes included: incidence of alloimmunization; outcomes for neonates with and without the cognate antigen; and sensitivity and specificity of antibody titration testing in predicting hemolytic disease of the fetus and newborn (HDFN). RESULTS: Over 6 years, 128 pregnant women (0.4%) were alloimmunized with 162 alloantibodies; anti-E was the most common alloantibody (51/162; 31%). Intrauterine transfusions (IUTs) were employed in 2 (3%) of 71 mothers of cognate antigen positive (CoAg+) neonates. Of 74 CoAg+ neonates, 58% required observation alone, 23% intensive phototherapy, 9% top up transfusion, and 3% exchange transfusion; no fetal or neonatal deaths occurred. HDFN was diagnosed in 28% (21/74) of neonates; anti-D was the most common cause. The sensitivity and specificity of the critical gel titer >32 in predicting HDFN were 76% and 75%, respectively (negative predictive value 95%; positive predictive value 36%). The sensitivity and specificity of a positive direct antiglobulin test (DAT) in predicting HDFN were 90% and 58%, respectively (NPV 97%; PPV 29%). CONCLUSION: Morbidity and mortality related to HDFN was low; most alloimmunized pregnancies needed minimal intervention. Titers of >32 by gel warrant additional monitoring during pregnancy.

A case of mild HDFN caused by anti-C, anti-D, and anti-G: Diagnostic strategy and clinical significance of distinguishing anti-G from anti-D and anti-C.

Anti-G is commonly present with anti-D and anti-C and can confuse serological investigations. The differentiation of anti-G from anti-D and anti-C is particularly essential for the accurate diagnosis of hemolytic disease of the fetus and newborn (HDFN) and appropriate administration of anti-D immunoglobulin prophylaxis in Rhesus (Rh) negative women. We reported a rare case of anti-G together with anti-D and anti-C in a pregnant woman and her female neonate. The titers of IgG anti-D, anti-C, and anti-G in the woman were 256, 128, and 32, respectively. While the titers of IgG anti-D, anti-C, and anti-G in the neonate were 16, 8, and 4, respectively. The neonate experienced mild HDFN and only received phototherapy during hospitalization. This report discusses the diagnostic strategy and clinical significance of differentiating anti-G from anti-D and anti-C.

[Effect of 2Me, DTT, ZAAP and Enzyme on JMH Antigen on the Surface of Human Erythrocytes].

OBJECTIVE: To explore the the effects of 2-Me, DTT, papain, pineapple protease and ZZAP on the antigenicity of JMH antigen of human red blood cells (RBC) surface. METHODS: Firstly, human RBC were treated with 2-Me, DTT, pineapple protease, papain and ZZAP reagents, respectively. The antigenicity of JMH antigen on human RBC surface was detected and analyzed by flow cytometry. RESULTS: Flow cytometric analysis found that compared with level before treatment, the antigenicity of JMH antigen on RBC surface was significantly reduced after 2-Me treatment, the positive rate of JMH antigen: 69.5%±4.5% vs 56.5%±3.4% (t=12.44, P＜0.01); fluorescence intensity: 4906±317 vs 3003±165 (t=11.84, P＜0.01). The antigenicity of JMH antigen on RBC surface significantly increased after DTT treatment, showing the positive rate of JMH antigen: 61.7%±3.8% vs 75.5±4.9% (t=16.57, P＜0.01), fluorescence intensity: 4044±294 vs 4854±319 (t=15.46, P＜0.01). However, both bromelain and papain could significantly reduce the antigenicity of JMH antigen on the RBC surface, Bromelain: the positive rate of JMH antigen: 62.2%±3.8% vs 8.8%±1.2% (t=26.44, P＜0.01), fluorescence intensity: 4263±273 vs 1444±212 (t=19.27, P＜0.01); Papain: the positive rate of JMH antigen: 62.8%±3.6% vs 8.8%±1.5% (t=21.38, P＜0.01), fluorescence intensity: 4389±284 vs 1458±230 (t=17.49, P＜0.01). The flow cytometric analysis revealed that ZZAP treatment significantly reduced the antigenicity of JMH antigen on the RBC surface, the positive rate of JMH antigen: 62.2%±4.4% vs 48.2%±4.1% (t=14.87, P＜0.01), fluorescence intensity: 4106±263 vs 2063±175 (t=17.49, P＜0.01). CONCLUSION: The treatment with 2-Me can reduce the antigenicity of JMH antigen on human RBC surface. The antigenicity of JMH antigen on human RBC surface increased after DTT treatment. The antigenicity of JMH antigen on human RBC surface significantly reduces after the treatment with pineapple protease or papain. ZZAP treatment can reduce the antigenicity of JMH antigen on the RBC surface.

Effect of 2Me, DTT, ZAAP and Enzyme on JMH Antigen on the Surface of Human Erythrocytes / 中国实验血液学杂志

OBJECTIVE@#To explore the the effects of 2-Me, DTT, papain, pineapple protease and ZZAP on the antigenicity of JMH antigen of human red blood cells (RBC) surface.@*METHODS@#Firstly, human RBC were treated with 2-Me, DTT, pineapple protease, papain and ZZAP reagents, respectively. The antigenicity of JMH antigen on human RBC surface was detected and analyzed by flow cytometry.@*RESULTS@#Flow cytometric analysis found that compared with level before treatment, the antigenicity of JMH antigen on RBC surface was significantly reduced after 2-Me treatment, the positive rate of JMH antigen: 69.5%±4.5% vs 56.5%±3.4% (t=12.44, P＜0.01); fluorescence intensity: 4906±317 vs 3003±165 (t=11.84, P＜0.01). The antigenicity of JMH antigen on RBC surface significantly increased after DTT treatment, showing the positive rate of JMH antigen: 61.7%±3.8% vs 75.5±4.9% (t=16.57, P＜0.01), fluorescence intensity: 4044±294 vs 4854±319 (t=15.46, P＜0.01). However, both bromelain and papain could significantly reduce the antigenicity of JMH antigen on the RBC surface, Bromelain: the positive rate of JMH antigen: 62.2%±3.8% vs 8.8%±1.2% (t=26.44, P＜0.01), fluorescence intensity: 4263±273 vs 1444±212 (t=19.27, P＜0.01); Papain: the positive rate of JMH antigen: 62.8%±3.6% vs 8.8%±1.5% (t=21.38, P＜0.01), fluorescence intensity: 4389±284 vs 1458±230 (t=17.49, P＜0.01). The flow cytometric analysis revealed that ZZAP treatment significantly reduced the antigenicity of JMH antigen on the RBC surface, the positive rate of JMH antigen: 62.2%±4.4% vs 48.2%±4.1% (t=14.87, P＜0.01), fluorescence intensity: 4106±263 vs 2063±175 (t=17.49, P＜0.01).@*CONCLUSION@#The treatment with 2-Me can reduce the antigenicity of JMH antigen on human RBC surface. The antigenicity of JMH antigen on human RBC surface increased after DTT treatment. The antigenicity of JMH antigen on human RBC surface significantly reduces after the treatment with pineapple protease or papain. ZZAP treatment can reduce the antigenicity of JMH antigen on the RBC surface.

Maternal red blood cell alloimmunization requiring intrauterine transfusion: a comparative study on management and outcome depending on the type of antibody.

BACKGROUND: The antibody primarily responsible for fetal anemia may influence treatment and prognosis. The primary objective was to compare ante- and postnatal management and the outcomes of maternal red blood cell (RBC) alloimmunizations according to the antibody involved. The secondary objective was to compare anti-D alloimmunizations according to associated number of antibodies. STUDY DESIGN AND METHODS: A single-center study from 1999 to 2015 including maternal RBC alloimmunizations requiring intrauterine transfusion (IUT) was conducted. Patients were classified according to the antibody involved: anti-D, other Rh (anti-c and anti-E), and anti-K1. Obstetric data, IUT characteristics, and neonatal outcome were compared. A specific study on the anti-D, when isolated or associated, was then conducted. RESULTS: There were 106 pregnancies included, with 77.4% having anti-D, 9.4% having another anti-Rh (Rh group), and 13.2% having anti-K1. No significant difference between the anti-D and Rh groups was found for management and prognosis. The hemoglobin level in the first IUT was higher in the anti-D group than in the Kell group (6.8 vs. 4.7 g/dL, p = 0.008). Newborns in the anti-D group had significantly higher bilirubin levels and phototherapy duration than those in the Kell group. The mean estimated daily decrease in hemoglobin and that between the first two IUTs were lower with an isolated anti-D, compared with anti-D associated with two antibodies (p = 0.04). CONCLUSION: Anti-K1 alloimmunizations seem to cause more severe fetal anemia than anti-D alloimmunizations. Moreover, a decrease in hemoglobin appears to be more rapid when anti-D is associated with other antibodies.

Prevalence of positive direct antiglobulin test and clinical outcomes in Surinamese newborns from D-negative women.

BACKGROUND: In low-resource countries, screening for D antibodies to detect pregnancies at risk for hemolytic disease of the newborn is not routine practice. Retrospective data showed that 5.5% of Surinamese newborns of D-negative women had a positive direct antiglobulin test (DAT), indicating the presence of maternal antibodies against fetal antigens. Here, the frequency and clinical relevance of DAT positivity is evaluated. STUDY DESIGN AND METHODS: Between April 2015 and June 2016, an observational, multicenter cohort study was undertaken among Surinamese newborns born to D-negative women. In newborns, the DAT was performed, and clinical outcomes between DAT-negative and DAT-positive newborns were compared. RESULTS: Of the 232 evaluable newborns, 19 (8.2%) had a positive DAT, of which 11 of 15 antibody-tested newborns had D antibodies. DAT-positive newborns had lower hemoglobin levels (p = 0.02) and a trend toward higher bilirubin concentrations (p = 0.09) in the first days of life compared with DAT-negative newborns. DAT-positive newborns were admitted more frequently (p = 0.02), needed phototherapy treatment almost four times as often as DAT-negative newborns (26% vs. 7%; p = 0.008), and therapy took 2 days longer (p = 0.01). Exchange transfusions were performed in two newborns with D antibodies, both complicated with sepsis. The hospital stay was 2.5 days longer for DAT-positive newborns (p = 0.007). Overall, the prevalence of hemolytic disease of the newborn requiring treatment was 2.2% among the whole cohort of newborns. CONCLUSION: We found a high prevalence of DAT positivity with substantial need for hyperbilirubinemia treatment in newborns in Suriname. These results stress the necessity for better management procedures in D-negative women.

Targeted antenatal anti-D prophylaxis program for RhD-negative pregnant women - outcome of the first two years of a national program in Finland.

INTRODUCTION: The aim of this study was to assess the accuracy of the non-invasive fetal RHD test at 24-26 weeks of gestation as part of the national antenatal screening program to target routine antenatal anti-D prophylaxis (RAADP) at 28-30 weeks at women carrying an RhD-positive fetus. MATERIAL AND METHODS: A prospective cohort study involving all maternity care centers and delivery hospitals in Finland between February 2014 and January 2016. Fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed with real-time polymerase chain reaction in a centralized setting. The results were systematically compared with the serological newborn RhD typing. The main outcome measure was the accuracy of the fetal RHD assay; the secondary variable was compliance with the newly introduced RAADP program. RESULTS: Fetal RHD was screened from 10 814 women. For the detection of fetal RHD, sensitivity was 99.99% [95% confidence interval (CI) 99.92-99.99] and specificity 99.81% (95% CI 99.60-99.92). One false-negative and seven false-positive results were reported by the delivery hospitals in two years. The negative predictive value of the test was 99.97% (95% CI 99.81-99.99). At the end of the study period, over 98% of the RhD-negative women participated in the new screening program. CONCLUSIONS: The targeted RAAPD program was implemented effectively in the national maternity care program in Finland. An accurate fetal RHD screening test allows discontinuation of newborn testing without risking the postnatal prophylaxis program. In the future, the main area to investigate will be the clinical effect of RAADP on subsequent pregnancies.

Anti-D in a mother, hemizygous for the variant RHD*DNB gene, associated with hemolytic disease of the fetus and newborn.

BACKGROUND: Individuals with the partial D phenotype when exposed to D+ red blood cells (RBCs) carrying the epitopes they lack may develop anti-D specific for the missing epitopes. DNB is the most common partial D in Caucasians and the clinical significance for anti-D in these individuals is unknown. STUDY DESIGN AND METHODS: This article describes the serologic genotyping results and clinical manifestations in two group D+ babies of a mother presenting as group O, D+ with alloanti-D. RESULTS: The mother was hemizygous for RHD*DNB gene and sequencing confirmed a single-nucleotide change at c.1063G>A. One baby (group A, D+) displayed bilirubinemia at birth with a normal hemoglobin level. Anti-A and anti-D were eluted from the RBCs. For the next ongoing pregnancy, the anti-D titer increased from 32 to 256. On delivery the baby typed group O and anti-D was eluted from the RBCs. This baby at birth exhibited anemia, reticulocytosis, and hyperbilirubinemia requiring intensive phototherapy treatment from Day 0 to Day 9 after birth and was discharged on Day 13. Intravenous immunoglobulin was also administered. Both babies were heterozygous for RHD and RHD*DNB. CONCLUSION: The anti-D produced by this woman with partial D DNB resulted in a case of hemolytic disease of the fetus and newborn (HDFN) requiring intensive treatment in the perinatal period. Anti-D formed by women with the partial D DNB phenotype has the potential to cause HDFN where the fetus is D+. Women carrying RHD*DNB should be offered appropriate prophylactic anti-D and be transfused with D- RBCs if not already alloimmunized.

Red cell alloimmunization in RhD positive pregnant women and neonatal outcome.

The frequency of red blood cell (RBC) alloimmunization in RhD positive pregnant women is not known in our population. We planned to determine its frequency and correlation with neonatal outcome. We included 1000 RhD positive pregnant women: 500 had 'normal pregnancy' (Group I) and another 500 had 'high risk pregnancy' (Group II). ABO and extended Rh phenotyping were done by tube technique, antibody screening and identification by gel technique. For alloimmunized women, the paternal and neonatal ABO and extended Rh typing were done. Neonatal direct antiglobulin test (DAT) was also done and their clinical outcome observed. The frequency of RBC alloimmunization was 0.7% (7/1000) and all these women were from group II (p = 0.015). The alloantibodies were anti-E (85.7%), anti-c (71.4%), anti-Cw (14.3%) and anti-S (14.3%). Also, 6 women had history of transfusion (p < 0.01). Of the 7 neonates born to alloimmunized mothers, 4 (57.14%) had a positive DAT. The mean duration of phototherapy was higher in the DAT positive neonates (p < 0.01) and 2 (50%) required exchange transfusion. Thus, the frequency of alloimmunization was 0.7% in RhD positive pregnant women. High risk pregnancies and antenatal patients having a history of blood transfusion should be considered for regular antibody screening.

Third trimester screening for alloimmunisation in Rhc-negative pregnant women: evaluation of the Dutch national screening programme.

OBJECTIVE: To evaluate the effect of red blood cell (RBC) antibody screening in the 27th week of pregnancy in Rhc-negative women, on detection of alloimmunisation, undetected at first trimester screening ('late' alloimmunisation), and subsequent haemolytic disease of the fetus and newborn (HDFN), to assess risk factors for late alloimmunisation. DESIGN: Prospective cohort and nested case-control study. SETTING: The Netherlands. POPULATION: Two-year nationwide cohort. METHODS: Prospective inclusion of Rhc-negative women with negative first trimester screening and of screen-negative controls. Assessment of incidence and numbers needed to screen (NNS) of late alloimmunisation and HDFN; logistic regression analysis to establish risk factors for late alloimmunisation. MAIN OUTCOME MEASURES: Late alloimmunisation, HDFN. RESULTS: Late alloimmunisation occurred in 99 of 62 096 (0.159%) Rhc-negative women; 90% had c/E antibodies and 10% non-Rhesus antibodies. Severe HDFN (fetal/neonatal transfusion) occurred in two of 62 096 (0.003%) of Rhc-negative women and 2% of late alloimmunisations; moderate HDFN (phototherapy) occurred in 20 children [22.5%; 95% confidence interval (CI), 13.8-31.1%]. Perinatal survival was 100%. The NNS to detect one HDFN case was 2823 (31 048 for severe, 3105 for moderate HDFN). Significant risk factors were former blood transfusion [odds ratio (OR), 10.4; 95% CI, 1.14-94.9], parity (P-1: OR, 11.8; 95% CI, 3.00-46.5; P > 1: OR, 7.77; 95% CI, 1.70-35.4) and amniocentesis/chorionic villus sampling during current pregnancy (OR, 9.20; 95% CI, 1.16-72.9). CONCLUSIONS: Additional screening of Rhc-negative women improved the detection of late alloimmunisation and HDFN, facilitating timely treatment, with a NNS of 2823. Independent risk factors for late alloimmunisation were blood transfusion, parity and chorionic villus sampling/amniocentesis in the current pregnancy. The occurrence of most factors before the current pregnancy suggests a secondary immune response explaining most late alloimmunisations. TWEETABLE ABSTRACT: Third trimester screening for alloimmunisation in Rhc-neg women improves detection and treatment of severe HDFN.

[Case of Rh (-) patient's right lobectomy of the liver with massive hemorrhage evading allogeneic blood transfusion by hemodilutional autologous blood transfusion].

A 44-year-old man (ASA-PS 1) underwent right lobectomy of the liver under total intravenous anesthesia with propofol, remifentanil, ketamine and rocuronium. In order to evade allogeneic blood transfusion, 1,200 g of the patient's blood was taken and hemodilution was induced for autologous blood transfusion (HAT) after the induction of anesthesia. As intraoperative blood loss amounted to about 4,000 g, Hb level decreased from 13.6 to 6.2 g x dl(-1). However, as intraoperative hemodynamics was relatively stable with crystalloidal and colloidal transfusion with no ischemic change on ECG and no metabolic acidosis, autologous blood transfusion was withheld. After returning the autologous blood, Hb increased to 9.8 g x dl(-1). Any postoperative complications related to the low Hb level were not recognized. HAT is a useful method to evade or at least decrease the amount of allogeneic blood transfusion by anesthesiologists.

Update on prenatal care.

Many elements of routine prenatal care are based on tradition and lack a firm evidence base; however, some elements are supported by more rigorous studies. Correct dating of the pregnancy is critical to prevent unnecessary inductions and to allow for accurate treatment of preterm labor. Physicians should recommend folic acid supplementation to all women as early as possible, preferably before conception, to reduce the risk of neural tube defects. Administration of Rho(D) immune globulin markedly decreases the risk of alloimmunization in an RhD-negative woman carrying an RhD-positive fetus. Screening and treatment for iron deficiency anemia can reduce the risks of preterm labor, intrauterine growth retardation, and perinatal depression. Testing for aneuploidy and neural tube defects should be offered to all pregnant women with a discussion of the risks and benefits. Specific genetic testing should be based on the family histories of the patient and her partner. Physicians should recommend that pregnant women receive a vaccination for influenza, be screened for asymptomatic bacteriuria, and be tested for sexually transmitted infections. Testing for group B streptococcus should be performed between 35 and 37 weeks' gestation. If test results are positive or the patient has a history of group B streptococcus bacteriuria during pregnancy, intrapartum antibiotic prophylaxis should be administered to reduce the risk of infection in the infant. Intramuscular or vaginal progesterone should be considered in women with a history of spontaneous preterm labor, preterm premature rupture of membranes, or shortened cervical length (less than 2.5 cm). Screening for diabetes should be offered using a universal or a risk-based approach. Women at risk of preeclampsia should be offered low-dose aspirin prophylaxis, as well as calcium supplementation if dietary calcium intake is low. Induction of labor may be considered between 41 and 42 weeks' gestation.

Routine testing of fetal Rhesus D status in Rhesus D negative women using cell-free fetal DNA: an investigation into the preferences and information needs of women.

OBJECTIVE: The goal of this study is to investigate women's preferences and information needs for routine implementation of fetal Rhesus D (RhD) typing using cell-free fetal DNA. METHODS: A questionnaire was developed following focus groups and interviews with both health professionals and RhD negative (RhD-) women offered fetal RhD genotyping within a research study and distributed to RhD- women attending routine antenatal appointments in four National Health Service hospitals. Current knowledge of blood types, anti-D administration, fetal RhD genotyping and future practices were explored. RESULTS: A total of 19 respondents participated in interviews and focus groups, and 270 respondents completed the questionnaires. Questionnaire respondents overwhelmingly felt that the test should be offered to all RhD- women (92.1%), and 75.9% said that they would accept this test. Most were happy to have the test even if it involved extra blood tests (89.3%) or appointments (79%). The knowledge of blood groups was poor. Although 90.7% knew that the baby could have a different blood group from themselves, only 34% knew that blood groups are inherited from both parents. More than 40% were not aware that anti-D would not be required if their baby was RhD-. CONCLUSIONS: Women would welcome the introduction of routine fetal RhD genotyping. Information leaflets and training of midwives will be essential for implementation to ensure good understanding regarding testing.

Postnatal outcome in neonates with severe Rhesus c compared to rhesus D hemolytic disease.

BACKGROUND: Neonates with Rhesus c (Rh c) hemolytic disease of the fetus and newborn (HDFN) are often managed in the same way as neonates with Rhesus D (Rh D) HDFN, although evidence to support this policy is limited. The objective of this study was to evaluate neonatal outcome in severe Rh c HDFN compared to Rh D HDFN. STUDY DESIGN AND METHODS: A retrospective study of (near-)term neonates with severe Rh c (n = 22) and Rh D HDFN (n = 103; without additional antibodies) admitted to the Leiden University Medical Center between January 2000 and October 2011 was conducted. The need for intrauterine transfusions (IUTs), phototherapy, exchange transfusions (ETs), and top-up transfusions up to 3 months of age were recorded and compared between both groups. RESULTS: Although there was a trend for a slightly more severe antenatal course for Rh D HDFN reflected by an earlier need for and higher number of IUTs (median [interquartile range], 2 [1.5-4] vs. 2 [1-2] in Rh c HDFN; p = 0.070), no significant differences were found for the postnatal course between Rh c and Rh D group in days of phototherapy (mean, Days 4.8 and 4.6, respectively; p = 0.569), need for ET (50% vs. 44%, respectively; p = 0.589), and top-up transfusions (62% vs. 78%, respectively; p = 0.128). CONCLUSION: Postnatal outcome in neonates with severe Rh c HDFN is similar compared to neonates with severe Rh D hemolytic disease in terms of days of phototherapy, need for ET, and need for top-up transfusions. These results justify a similar postnatal management of neonates with Rh D and Rh c HDFN.

Anti-D in pregnant women with the RHD(IVS3+1G>A)-associated DEL phenotype.

BACKGROUND: Pregnant women with the DEL phenotype appear to be D- by routine serology. Women with DEL phenotypes that show a partial D-like epitope loss may develop anti-D. It has been proposed that this alloantibody could have a deleterious effect with respect to hemolytic disease in the fetus and newborn. CASE REPORTS: Two pregnant women, one in Australia and one in Germany, were serotyped as D- and were sensitized to the D antigen. Noninvasive fetal RHD genotyping was performed to plan pregnancy management. RESULTS: In both cases the fetal RHD status could not be assigned due to the presence of a maternal DEL allele. This was suspected through detection of high RHD amplicon levels during quantitative polymerase chain reaction. For both cases extended molecular typing of the maternal genomic DNA revealed a RHD(IVS3+1G>A) allele. For case one, the D+ infant developed a mild hemolytic disease requiring phototherapy. In the second case a D- (or DEL) newborn was unaffected. CONCLUSION: Fetal genotyping from maternal plasma reveals RHD variants in pregnant women with anti-D. Fetuses and newborns of sensitized pregnant women carrying the RHD(IVS3+1G>A) allele are at risk of hemolytic disease.

[Fetomaternal anti-RH3, -4 (anti-E and anti-c) rhesus isoimmunization: a case report]. / Allo-immunisation fœto-maternelle rhésus anti-RH3, 4 (anti-E et anti-c) : à propos d'un cas.

Hemolytic disease of the newborn caused by maternal isoimmunization has been decreasing over the past 10 years because of prophylactic treatment with anti-RH1 (anti-D) immunoglobulin. Nevertheless, there is an increase in the incidence of both relative and absolute numbers of non-RH1 red-cell maternofetal isoimmunizations, essentially anti-RH4 (anti-c), anti-RH3 (anti-E), and anti-Kell. In 8 to 14% of cases, multispecificity antibodies are present, the most common combination being the association of anti-RH3 and -4. Despite absence of specific prophylactic therapy, anti-RH4 isoimmunization could be as severe as anti-RH1 ; as for anti-RH3, it is usually associated with mild to moderate clinical manifestations. Nevertheless, there are few publications on anti-RH3, -4 maternofetal isoimmunization with a bias toward the most severe cases being reported. We report here a case of nonsevere maternofetal anti-RH3, -4 isoimmunization complicated with severe hyperbilirubinemia and delayed profound anemia. Hyperbilirubinemia was controlled using intensive phototherapy. Although anemia was absent at birth, it appeared progressively with a nadir at 7.8 g/dL at 1-month postnatal age. Blood counts were monitored for 3 months but the patient did not require red blood cell transfusion. This report underlines the need for a prolonged and rigorous pediatric follow-up of children born in the context of maternofetal isoimmunization after the acute neonatal period. Furthermore, it stresses the necessity of DAT testing in all pregnant women, even those who are RH1-positive.