Rh Blood Group Antigens and Alloimmunization Risk of Pregnant Women in South Western, Nigeria.

BACKGROUND: Rh blood group antigens are the second most important blood group antigens in clinical transfusion due to their immunogenicity and prevalence. Childbirth, miscarriage, and other obstetrics events are risk factors for alloimmunization in women which increases the likelihood of haemolytic blood transfusion reaction and hemolytic disease of the fetal/newborn (HDNF/B). Even though there are several data on the RhD status of our populations. However, there is a dearth of data on pregnant women's C, E, c, and e status, their alloimmunization risk, and rates in Nigeria. OBJECTIVES: This study aims to provide information on the distribution of the Rh major antigens and risk factors for alloimmunization in pregnant women in southwestern Nigeria. MATERIALS AND METHODS: This was a descriptive cross-sectional study of 133 pregnant women attending routine ante-natal clinics. Questionnaires were administered to collect biodata and obstetrics history. ABO blood grouping and Rh phenotyping were carried out on their blood samples using RAPID LABS Monoclonal Rhesus Typing Reagent. RESULTS AND DISCUSSION: Rh blood group antigen c was present in 100% of the women, followed by e (98.5%) and D (95.5%). C and E are the least prevalent antigens and probably the ones to which antibodies may be formed. The commonest Rh phenotype was Dce. Of all the pregnant women, alloimmunization was present in 0.8%. Of those who were RhD negative, alloimmunization was present in 16.7%. Pregnant women are more likely to be alloimmunized against C and E antigens than c and e antigens due to their low and high frequencies respectively.

CONTEXTE: Les antigènes du groupe sanguin Rh sont les seconds plus importants en transfusion clinique en raison de leur immunogénicité et de leur prévalence. L'accouchement, la fausse couche et d'autres événements obstétriques sont des facteurs de risque d'alloimmunisation chez les femmes, augmentant ainsi la probabilité de réactions hémolytiques lors de transfusions sanguines et de maladies hémolytiques du fœtus/nouveau-né (HDNF/B). Bien qu'il existe plusieurs données sur le statut RhD de nos populations, il y a un manque de données sur le statut des antigènes C, E, c et e chez les femmes enceintes, leur risque d'alloimmunisation et les taux associés au Nigéria. OBJECTIFS: Cette étude vise à fournir des informations sur la distribution des principaux antigènes Rh et les facteurs de risque d'alloimmunisation chez les femmes enceintes dans le sud-ouest du Nigéria. MÉTHODOLOGIE: Il s'agit d'une étude descriptive transversale de 133 femmes enceintes fréquentant les cliniques prénatales de routine. Des questionnaires ont été administrés pour collecter des données biodémographiques et des antécédents obstétriques. La détermination des groupes sanguins ABO et le phénotypage Rh ont été réalisés sur leurs échantillons de sang à l'aide du réactif de typage Rh monoclonal RAPID LABS. RÉSULTATS ET DISCUSSION: L'antigène c du groupe sanguin Rh était présent chez 100 % des femmes, suivi de e (98,5 %) et D (95,5 %). Les antigènes C et E sont les moins prévalents et probablement ceux contre lesquels des anticorps peuvent être formés. Le phénotype Rh le plus courant était Dce. Parmi toutes les femmes enceintes, l'alloimmunisation était présente chez 0,8 %. Parmi celles qui étaient RhD négatives, 'alloimmunisation était présente chez 16,7 %. Les femmes enceintes sont plus susceptibles de développer une alloimmunisation contre les antigènes C et E que contre les antigènes c et e en raison de leurs fréquences respectives faibles et élevées. MOTS-CLÉS: Antigènes du groupe sanguin Rh, Phénotype, Alloanticorps érythrocytaires, Femmes enceintes.

Neonatal and Obstetrical Outcomes of Pregnancies Complicated by Alloimmunization.

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 ∼4% 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.

Low titer group O whole blood and risk of RhD alloimmunization: Rationale for use in Finland.

BACKGROUND: Prehospital low-titer group O whole blood (LTOWB) used for patients with life-threatening hemorrhage is often RhD positive. The most important complication following RhD alloimmunization is hemolytic disease of the fetus and newborn (HDFN). Preceding clinical use of RhD positive LTOWB, we estimated the risk of HDFN due to LTOWB prehospital transfusion in the Finnish population. STUDY DESIGN AND METHODS: We collected data on prehospital transfusions in Tampere and Helsinki University Hospital areas. Using the mean of reported alloimmunization rates in trauma studies (24%) and a higher reported rate representing trauma patients of 13-50 years old (42.7%), we estimated the risk of HDFN and extrapolated it to the whole of Finland. RESULTS: We estimated that in Finland, with the current prehospital transfusion rate we would see 1-3 cases of severe HDFN due to prehospital LTOWB transfusions every 10 years, and fetal death due to HDFN caused by LTOWB transfusion less than once in 100 years. DISCUSSION: The estimated risk of serious HDFN due to prehospital LTOWB transfusion in the Finnish population is similar to previous estimates. As Finland routinely screens expectant mothers for red blood cell antibodies and as the contemporary treatment of HDFN is very effective, we support the prehospital use of RhD positive LTOWB in all patient groups.

Risk factors for RhD immunisation in a high coverage prevention programme of antenatal and postnatal RhIg: a nationwide cohort study.

OBJECTIVE: To evaluate which risk factors for RhD immunisation remain, despite adequate routine antenatal and postnatal RhIg prophylaxis (1000 IU RhIg) and additional administration of RhIg. The second objective was assessment of the current prevalence of RhD immunisations. DESIGN: Prospective cohort study. SETTING: The Netherlands. POPULATION: Two-year nationwide cohort of alloimmunised RhD-negative women. METHODS: RhD-negative women in their first RhD immunised pregnancy were included for risk factor analysis. We compared risk factors for RhD immunisation, occurring either in the previous non-immunised pregnancy or in the index pregnancy, with national population data derived from the Dutch perinatal registration (Perined). RESULTS: In the 2-year cohort, data from 193 women were eligible for analysis. Significant risk factors in women previously experiencing a pregnancy of an RhD-positive child (n = 113) were: caesarean section (CS) (OR 1.7, 95% CI 1.1-2.6), perinatal death (OR 3.5, 95% CI 1.1-10.9), gestational age >42 weeks (OR 6.1, 95% CI 2.2-16.6), postnatal bleeding (>1000 ml) (OR 2.0, 95% CI 1.1-3.6), manual removal of the placenta (MRP) (OR 4.3, 95% CI 2.0-9.3); these factors often occurred in combination. The miscarriage rate was significantly higher than in the Dutch population (35% versus 12.-5%, P < 0.001). CONCLUSION: Complicated deliveries, including cases of major bleeding and surgical interventions (CS, MRP), must be recognised as a risk factor, requiring estimation of fetomaternal haemorrhage volume and adjustment of RhIg dosing. The higher miscarriage rate suggests that existing RhIg protocols need adjustment or better compliance. TWEETABLE ABSTRACT: Complicated delivery (caesarean section, manual removal placenta, major bleeding) is the most valid risk factor for RhD immunization despite antenatal and postnatal RhIg.

Time points and risk factors for RhD immunizations after the implementation of targeted routine antenatal anti-D prophylaxis: A retrospective nationwide cohort study.

INTRODUCTION: Targeted routine antenatal anti-D prophylaxis was introduced to the national prophylaxis program in Finland in late 2013. The aim of this study was to assess the incidence, time-points, and risk factors for Rhesus D immunization after the implementation of routine antenatal anti-D prophylaxis, in all women in Finland with antenatal anti-D antibodies detected in 2014-2017. MATERIAL AND METHODS: In a nationwide population-based retrospective cohort study, the incidence, time-points, and risk factors of anti-D immunizations were analyzed. Information on antenatal screening was obtained from the Finnish Red Cross Blood Service database, and obstetric data from hospital records and the Finnish Medical Birth Register. RESULTS: The study included a total of 228 women (197 with complete data for all pregnancies). After the implementation of routine antenatal anti-D prophylaxis, the prevalence of pregnancies with anti-D antibodies decreased from 1.52% in 2014 to 0.88% in 2017, and the corresponding incidence of new immunizations decreased from 0.33% to 0.10%. Time-points for detection of new anti-D antibodies before and after 2014 were the first screening sample at 8-12 weeks of gestation in 52% vs 19%, the second sample at 24-26 weeks in 20% vs 50%, and the third screening at 36 weeks in 28% vs 32%. CONCLUSIONS: The incidence of new anti-D immunizations decreased as expected after the implementation of routine antenatal anti-D prophylaxis. True failures are rare and they mainly occur when the prophylaxis is not given appropriately, suggesting a need for constant education of healthcare professionals on the subject.

Hemolytic disease of the fetus and newborn due to Rh(D) incompatibility: A preventable disease that still produces significant morbidity and mortality in children.

In the mid-20th century, Hemolytic Disease of the Fetus and Newborn, caused by maternal alloimmunization to the Rh(D) blood group antigen expressed by fetal red blood cells (i.e., "Rh disease"), was a major cause of fetal and neonatal morbidity and mortality. However, with the regulatory approval, in 1968, of IgG anti-Rh(D) immunoprophylaxis to prevent maternal sensitization, the prospect of eradicating Rh disease was at hand. Indeed, the combination of antenatal and post-partum immunoprophylaxis is ~99% effective at preventing maternal sensitization to Rh(D). To investigate global compliance with this therapeutic intervention, we used an epidemiological approach to estimate the current annual number of pregnancies worldwide involving an Rh(D)-negative mother and an Rh(D)-positive fetus. The annual number of doses of anti-Rh(D) IgG required for successful immunoprophylaxis for these cases was then calculated and compared with an estimate of the annual number of doses of anti-Rh(D) produced and provided worldwide. Our results suggest that ~50% of the women around the world who require this type of immunoprophylaxis do not receive it, presumably due to a lack of awareness, availability, and/or affordability, thereby putting hundreds of thousands of fetuses and neonates at risk for Rh disease each year. The global failure to provide this generally acknowledged standard-of-care to prevent Rh disease, even 50 years after its availability, contributes to an enormous, continuing burden of fetal and neonatal disease and provides a critically important challenge to the international health care system.

Red cell alloimmunization: A 2020 update.

Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of alloimmune-induced fetal anemia make this condition an exemplar for contemporary practice in fetal therapy. Since survival is now an expectation, attention has turned to optimization of long-term outcomes following an alloimmunized pregnancy. In this review, the current management of red cell alloimmunization is described. Current research and future directions are discussed with particular emphasis on later life outcomes after alloimmune fetal anemia.

Rhesus D alloimmunization in pregnancy from 1996 to 2015 in Iceland: a nation-wide population study prior to routine antenatal anti-D prophylaxis.

BACKGROUND: Rhesus D (RhD) incompatibility is still the most important cause of hemolytic disease of the fetus and newborn (HDFN) worldwide. The aim of this study was to investigate the incidence, causes, and consequences of anti-D alloimmunizations in pregnancy in Iceland, prior to implementation of targeted routine antenatal anti-D prophylaxis (RAADP) in 2018. STUDY DESIGN AND METHODS: This was a nation-wide cohort study of 130 pregnancies affected by RhD alloimmunization in Iceland in the period from 1996 through 2015. Data were collected from transfusion medicine databases, medical records, and the Icelandic Medical Birth Register. RESULTS: Of 130 RhD alloimmunizations, 80 cases (61.5%) represented new RhD immunization in the current pregnancy. Sensitization was discovered in the third trimester in 41 (51.3%) and occurred in the first pregnancy in 14 cases (17.5%). The most likely causative immunization event was the index pregnancy for 45 (56.25%), a previous pregnancy/birth for 26 (32.5%), abortion for 3 (3.75%), and unknown for 6 women (7.5%). Higher anti-D titers were associated with shorter gestational length, cesarean sections, positive direct antiglobulin test (DAT), and severe HDFN. Intrauterine transfusion (IUT) was performed in five pregnancies (3.8%), and 35 of 132 (26.5%) live-born neonates received treatment for HDFN; 32 received phototherapy (24.2%), 13 exchange transfusion (9.8%), and seven simple blood transfusion (5.3%). CONCLUSION: In about half of cases, RhD alloimmunization was caused by the index pregnancy and discovered in the third trimester. Thus, the newly implemented RAADP protocol should be effective in reducing the incidence of RhD immunization in Iceland in the future.

Phenotypic Classification of preterm Birth Among Multiparous Women: A Population-Based Cohort Study.

OBJECTIVE: The Global Alliance to Prevent Prematurity and Stillbirth developed a phenotypic classification for preterm birth using clinical presentation (rather than risk factors) to improve surveillance. The objective of this study was to determine distributions of preterm birth phenotypes and associations with Caesarean section, low Apgar score, and neonatal death in multiparous women, stratifying by first versus recurrent preterm births. METHODS: This population-based cohort study used the Better Outcomes Registry and Network (BORN) of multiparous women giving birth in hospital with a singleton after 20 weeks in Ontario from 2012 to 2014 (Canadian Task Force Classification II-2). RESULTS: In multiparous women with preterm birth, 29.6% had a history of recurrence, of whom 66.2% had at least one clinical condition associated with the phenotypic model, compared with 63.5% of first preterm births. In recurrent preterm births, criteria for maternal, fetal, and placental conditions were met in 44.5%, 37.9%, and 8.2%, respectively, compared with 36.8%, 39.0%, and 10.4%, respectively, of first preterm births. Associations of preterm birth with Caesarean section, low Apgar score, and neonatal death varied across clinical conditions but were similar between first and recurrent preterm births; for example, for recurrent preterm birth, Caesarean section for maternal, fetal, and placental conditions had odds ratios of 1.66 (95% confidence interval [CI] 1.32-2.07), 1.09 (95% CI 0.80-1.49), and 3.92 (95% CI 1.98-7.78), compared with first preterm birth odds ratios of 1.21 (95% CI 1.03-1.41), 0.92 (95% CI 0.77-1.10), and 6.24 (95% CI 4.07-9.56). CONCLUSION: This study provides novel evidence of the utility of the preterm birth phenotypic classification model by using stratification for previous preterm birth, a robust predictor-with variation in phenotypes in initial and recurrent preterm births.

Phenotypic Classification of Preterm Birth Among Nulliparous Women: A Population-Based Cohort Study.

OBJECTIVE: A classification model based on preterm birth clinical presentations (phenotypes) was proposed at the International Conference on Prematurity and Stillbirth, with calls for validation. This study sought to determine the distribution of clinical phenotypes of preterm birth among nulliparous women, their corresponding associations with maternal characteristics, and the odds ratios (ORs) of preterm Caesarean section and other adverse outcomes. METHODS: A population-based cohort study was performed of all nulliparous women with singleton pregnancies (>20 weeks) who gave birth in a hospital in Ontario between 2012 and 2014. Logistic regression models were used to estimate adjusted ORs (Canadian Task Force Classification II-2). RESULTS: Among 113 942 nulliparous women, 6.1% delivered at <37 weeks, at a mean gestational age of 33.9 weeks. Of those women, 34.1% did not meet the criteria for the presence of any clinical phenotype; 42.3% had one maternal, fetal, or placental condition; 22.3% had two clinical conditions; and 1.3% had three clinical conditions. The most common preterm birth phenotypes were worsening of maternal diseases (24.0%), intrauterine growth restriction (23.5%), and fetal distress (23.0%). Compared with preterm births without any significant clinical phenotype, those with maternal, fetal, or placental phenotypes were associated with increased odds of Caesarean section (adjusted ORs 2.70 [95% confidence interval [CI] 2.30-3.17], 1.66 [95% CI 1.36-2.03], and 6.49 [95% CI 4.29-9.80], respectively). CONCLUSION: Approximately two thirds of nulliparous preterm births were grouped into distinct clinical phenotypes. This study demonstrated that outcomes varied across phenotypes, thus providing evidence of benefit for the phenotypic classification model.

Prevalence and obstetric outcome of women with red cell antibodies in pregnancy at the Leeds Teaching Hospitals NHS Trust, West Yorkshire, England.

OBJECTIVE: The prevalence of red cell antibodies in pregnancy varies with ethnicity and geographical location, while the obstetric outcome depends on the available standard of care. Despite being the tertiary fetal medicine centre in West Yorkshire, the prevalence of red cell antibodies, and the outcome of pregnancies associated with these antibodies at the Leeds University Teaching Hospitals Trust remains unreported. This article aims to provide this information for the purpose of patient education and counselling. STUDY DESIGN: The data of pregnant women with red cell antibodies between January 2011 and December 2016 was obtained from the Trust's database and reconciled with the Fetal Medicine Unit records using Viewpoint©. Fetal anaemia requiring in utero transfusion (IUT) was defined as a Middle Cerebral Artery Peak Systolic Velocities ≥ 1.5multiple of the median expected for gestational age. The mean gestational age at delivery, and perinatal outcomes of the pregnancies were recorded. RESULT: Overall, 398 of the 96, 692 pregnant women that were screened had red cell antibodies, giving a prevalence of 1: 242 pregnancies. The Anti- E and Anti-M antibodies were the most common (114 women; 28.6%, and 112 women; 28.1% respectively), but did not cause fetal anaemia in isolation, while anti-D alloimmunization was the predominant indication for in-utero transfusion (IUT). Anti-DE and anti-Kell antibodies had the highest mean number of transfusions per pregnancy. The mean gestational age at delivery was 34 ± 2weeks. Post-transfusion fetal demise was recorded in two hydropic fetuses, both at a gestational age of 25 weeks; giving a transfusion-related mortality rate of 2.5%. CONCLUSION: The prevalence of red cell antibodies at West Yorkshire is lower compared with reports from other Caucasian populations.Nevertheless, these antibodies are important causes of iatrogenic preterm delivery and fetal morbidity. The prognosis is however good with prompt diagnosis and management.

Red blood cell alloimmunisation in transfusion-dependent thalassaemia: a systematic review.

BACKGROUND: Chronic red blood cell transfusion is the first-line treatment for severe forms of thalassaemia. This therapy is, however, hampered by a number of adverse effects, including red blood cell alloimmunisation. The aim of this systematic review was to collect the current literature data on erythrocyte alloimmunisation. MATERIALS AND METHODS: We performed a systematic search of the literature which identified 41 cohort studies involving 9,256 patients. RESULTS: The prevalence of erythrocyte alloimmunisation was 11.4% (95% CI: 9.3-13.9%) with a higher rate of alloimmunisation against antigens of the Rh (52.4%) and Kell (25.6%) systems. Overall, alloantibodies against antigens belonging to the Rh and Kell systems accounted for 78% of the cases. A higher prevalence of red blood cell alloimmunisation was found in patients with thalassaemia intermedia compared to that among patients with thalassaemia major (15.5 vs 12.8%). DISCUSSION: Matching transfusion-dependent thalassaemia patients and red blood cell units for Rh and Kell antigens should be able to reduce the risk of red blood cell alloimmunisation by about 80%.

Misinterpretation of blood group and antibody screen leading to serious errors in RhD immunoglobulin administration: A report on first two years of data from Serious Transfusion Incident Reporting program.

The Serious Transfusion Incident Reporting program (STIR) commenced haemovigilance in relation to RhD immunoglobulin (Ig) administration in 2015. During two years of reporting, 21 reports relating to RhD Ig administration were received. Thirty-three percent (7/21) were related to omission of RhD Ig, putting women at risk of RhD alloimmunisation and adverse consequences in future pregnancies. A recent case reported to STIR highlights poor communication and misinterpretation of pathology results leading to significant morbidity from haemolysis in the fetus. STIR makes recommendations related to education of staff and communication between clinical and laboratory staff to improve the safety of patient care.

Anti-D quantification in relation to anti-D titre, middle cerebral artery Doppler measurement and clinical outcome in RhD-immunized pregnancies.

BACKGROUND: The optimal strategy to monitor RhD-immunized pregnancies is not evident. Whether a quantitative analysis of anti-D antibodies adds valuable information to anti-D titre is unclear. The aim of this study was to evaluate the relevance of anti-D quantification in routine monitoring of RhD-immunized pregnancies. MATERIALS AND METHODS: In a retrospective study, 64 consecutive pregnancies in 61 immunized women with anti-D titre ≥128 at any time during pregnancy were included. According to routine, at titre ≥128, anti-D quantification was performed by flow cytometry and the peak systolic velocity in the middle cerebral artery was measured by ultrasound. Decisions for treatment with intrauterine blood transfusion were based on increased peak systolic velocity in the middle cerebral artery. RESULTS: Increasing anti-D concentrations correlated well to increasing anti-D titres, but at each titre value, there was a large interindividual variation, in the determined anti-D concentration. Intrauterine transfusions were initiated in 35 pregnancies according to algorithms based on ultrasound measurements, at anti-D concentrations of 2·4-619 IU/ml and titre 128-16 000. Sixty pregnancies resulted in a live-born child, three in miscarriage and one in termination of pregnancy. During the perinatal care in the neonatal intensive care unit, thirty-one of the neonates were treated with blood exchange transfusions and/or red cell transfusions and 47 were treated with phototherapy. CONCLUSION: Anti-D quantification does not add further information compared to anti-D titre, in defining a critical level to start monitoring RhD-immunized pregnancies with Doppler ultrasound.

Facilitators and barriers for RhD-immunized women to become and remain anti-D donors.

BACKGROUND: The successful introduction of prophylaxis with anti-RhD immunoglobulin has resulted in a significant decline of pregnancy-related RhD immunizations but also has decreased the availability of naturally immunized women as (new) anti-D donors. An influx of new donors is necessary to maintain a sufficient pool of anti-D donors. We investigated motivators, barriers, and predictors for anti-D donorship in RhD-immunized women. STUDY DESIGN AND METHODS: A mixed-methods design was applied, including focus group discussions and questionnaires. Two focus groups (including 11 women) served as input for the questionnaire. RESULTS: In total, 47.6% of 750 anti-D donors and potential donors completed the questionnaire (50.4% donors; 38% nondonors; 11.6% former donors). Almost 70% of the nondonors would have become donors if they had known about the possibility. Travel time investment was reported as a disadvantage; one-half of donors mentioned no disadvantages. Motivators for anti-D donorship were "doing something in return" (31.2%) and "preventing others having a sick child or losing a child" (33.9%). In multivariable analysis, living single (odds ratio, 5.8; p = 0.02) and living partnered without resident children (odds ratio, 7.9; p = 0.03), compared with living partnered with children, were predictors for anti-D donorship. Not being registered as an organ donor (odds ratio, 0.25; p < 0.001) predicted that the individual would not be an anti-D donor. CONCLUSION: The main barrier for anti-D donorship was a lack of knowledge. Positive predictors of anti-D donorship were living without resident children, altruism, and being registered as an organ donor. A blood bank should develop targeted recruitment strategies with a focus on spreading knowledge about anti-D donorship among RhD-immunized women.

No. 343-Routine Non-invasive Prenatal Prediction of Fetal RHD Genotype in Canada: The Time is Here.

The optimal management of the D-negative pregnant woman is now based on the non-invasive antenatal prediction of fetal D-blood group by cell-free DNA (cfDNA) in maternal plasma, with targeted prophylaxis for women carrying RHD-positive fetuses. This provides the optimal care for D-negative pregnant women and has been adopted as the standard approach in a growing number of countries around the world. This paper is the result of a consensus meeting of the Canadian National Rh Working Group, an interdisciplinary group formed to review the current status of fetal RHD genotyping based on cfDNA in Canada. The group, in collaboration with the SOGC Genetics committee, reviewed the benefits and challenges of implementing RHD genotyping with targeted prophylaxis in the context of the existing routine antenatal anti D prophylaxis program in Canada. The following summary statements and recommendations are based on this review. SUMMARY STATEMENTS: RECOMMENDATIONS.

[Intrauterine blood transfusion: Status report of 4years of practice in France (2011-2014)]. / Transfusions fœtales érythrocytaires : état des lieux sur 4 ans en France (2011­2014).

OBJECTIVES: The aim of our study was to evaluate in utero blood transfusion's (IUT) performed in France, among the French prenatal diagnosis centers in order to study the etiology of severe anemia requiring IUT. METHODS: We conducted a national retrospective descriptive study between 2011 and 2014. The data were collected using a survey sent by email to all French prenatal diagnosis centers. RESULTS: Among the 49 centers, 18 (38 %) had performed at least one IUT during the study period. The geographical repartition of these centers was appropriate for the "Aquitaine Pyrénées" region. Five centers performed 68 % of the national activity and one center performed 40 % the national activity. Each year, a mean of 204 IUTs were performed in 113 pregnancies. The principal etiology of severe fetal anemia requiring IUT was hemolytic disease of the fetus (69 % of the etiologies) with anti-RhD being the most prevalent antibody. The second etiology was represented by parvovirus B19 infection (17 % of IUTs). CONCLUSION: The French IUT activity was stable in numbers and indications during the study period. A national register could be set up in order to better evaluate prospectively the number of pregnancies concerned by IUT and to study the prevalence of hemolytic disease of the fetus due to anti-RhD antibodies.

Cancer type predicts alloimmunization following RhD-incompatible RBC transfusions.

BACKGROUND: Immunosuppressed, RhD-negative oncology patients tend to have lower rates of sensitization to the D antigen when they receive transfusion with RhD-positive blood components. Clinical factors associated with alloimmunization to the D antigen in RhD-negative oncology patients when they receive transfusion with RhD-positive red blood cells (RBCs) have not been well defined. STUDY DESIGN AND METHODS: This was a 4-year, retrospective analysis identifying RhD-negative oncology patients who received RhD-positive RBCs and were not previously alloimmunized to the D antigen. Age, sex, race, ABO group, primary oncology diagnosis, and numbers of RhD-incompatible RBC transfusions were recorded. The association between antibody formation and clinical factors was studied. The incidence of alloanti-D was calculated from a subsequent antibody-detection test performed at least 28 days after receipt of the first transfusion of RhD-positive RBCs. RESULTS: In total, 545 RhD-negative oncology patients received 4295 RhD-positive RBC transfusions. Of these, 76 (14%) became alloimmunized to the D antigen. Diagnosis type was the only factor significantly associated with responder status. The logistic regression model indicated that patients who had myelodysplastic syndrome or solid malignancies were more likely to be responders than those who had acute leukemia. CONCLUSION: We measured a 14% sensitization rate to the D antigen in our RhD-negative oncology population. The rate of alloimmunization was higher in patients who had solid cancers (22.6%) or myelodysplastic syndrome (23%) compared with those who had other hematologic malignancies (7%). Knowledge of diagnoses that predispose to RhD alloimmunization enables better utilization of RhD-negative RBCs during times of shortage.

A review of maternal alloimmunisation to Rh D in Northern Ireland.

OBJECTIVES: To estimate the current incidence of maternal sensitisation to Rhesus (Rh) D in Northern Ireland, examine adherence to recommendations for administration of anti-D immunoglobulin and identify potential causes for all cases of anti-D alloimmunisation sensitisation from January 2010 to September 2015. BACKGROUND: Post-partum anti-D immunoglobulin administered to Rh D-negative women and routine antenatal anti-D prophylaxis have greatly reduced the incidence of haemolytic disease of the fetus and newborn due to immune anti-D. Despite these measures, anti-D alloimmunisation sensitisation continues to occur, albeit much less frequently than in the past. METHODS/MATERIALS: This was a retrospective review of new sensitisations to Rh D detected in antenatal records between January 2010 and September 2015 in Northern Ireland. A review of patient notes and laboratory data was carried out to examine adherence to standards and identify potential causes of sensitisation. RESULTS: A total of 67 new sensitisations to Rh D were identified over a 69-month period, and the sensitisation rate for the full calendar years 2010-2014 was 0·310%. Only 4% of cases appear to have been preventable, with two cases involving failure to adhere to guidelines. CONCLUSION: A total 96% of sensitisations occurred despite full compliance with guidelines. In a large proportion, sensitisation occurred following delivery (51%). A change in practice in Northern Ireland is under consideration to increase the dose of anti-D immunoglobulin given following delivery from 500 to 1500 U in an attempt to reduce these sensitisations.

Alloimmunization against platelets, granulocytes and erythrocytes in multi-transfused patients in Iranian population.

BACKGROUND: This study aims at alloantibody screening, determination of the types of these antibodies in multiple-transfused patients with chronic hematologic diseases. PATIENTS AND METHODS: This descriptive study was performed on 240 patients with chronic hematological diseases referred to public hospitals in Iran. Single blood sample was taken and tested for the presence of antibodies. In case of a positive antibody screening, antibody identification was performed using granulocyte agglutination test (GAT), granulocyte indirect immunofluorescence test (GIIFT), platelet indirect immunofluorescence test (PIIFT), monoclonal antibody-specific immobilization of platelet antigen (MAIPA) and panel cells. RESULTS: Out of 240 patients, 105 patients (43.75 %) had been alloimmunized. The incidence of alloantibodies against red blood cells (RBCs) in positive alloantibodies patients were 84.76% (89/105). The most common alloantibody was against antigens of the kell (anti-K) and Rh (anti-E) and (anti D) systems (46.66%, 18.09% and 11.43% respectively). The overall incidence of anti- human leukocyte antigen (HLA) antibodies were 65.7% (69/105). Polymorphonuclear (PMN)-specific antibodies were found in 6.66% (7/105). Also from 105 patients, 14 patients had alloantibodies against platelet. DISCUSSION: In general, it is recommend that to decrease the rate of alloantibody synthesis, the packed cells should be cross matched for minor blood groups especially for Rh (E) and kell. In addition, the use of leukodepleted blood products can decrease the frequency of alloimmunization against platelet (PLT), PMN and HLA antigens.