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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., (© 2022 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

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., (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology.)

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., (© 2020 John Wiley & Sons, Ltd.)

Red blood cell alloimmunisation after transfusion of red blood cell concentrates carries a risk for every recipient. This risk is particularly high for patients with conditions such as sickle cell disease. However, red blood cell alloimmunisation can also occur after platelet concentrate transfusion. All blood group systems other than ABO are affected, and there are several mechanisms responsible for this alloimmunisation. The practical implications of this are a need to match red blood cell concentrates in all alloimmunised patients and, in pregnant women, recongnition of the risk of developing haemolytic disease of the foetus and newborn. Several measures can be taken to prevent alloimmunisation: in the case of the D antigen, for example, anti-RhD immunoglobulins can be infused before transfusing platelet concentrates from an RhD-positive donor in a RhD-negative recipient., (Copyright © 2020 Société française de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Background and Objectives: D-negative patients are at risk of developing an alloantibody to D (anti-D) if exposed to D during transfusion. The presence of anti-D can lead to haemolytic transfusion reactions and haemolytic disease of the newborn. Anti-D alloimmunization can also complicate allogeneic haematopoietic stem cell transplantation (HSCT) with haemolysis and increased transfusion requirements. The goal of this study was to determine whether cancer centres have transfusion practices intended to prevent anti-D alloimmunization with special attention in patients considered for HSCT., Methods and Materials: To understand transfusion practices regarding D-positive platelets in D-negative patients with large transfusion needs, we surveyed the 28 cancer centres that are members of the National Comprehensive Cancer Network ® (NCCN ® )., Results: Nineteen centres responded (68%). Most centres (79%) avoid transfusing D-positive platelets to RhD-negative patients when possible. Four centres (21%) avoid D-positive platelets only in D-negative women of childbearing age. If a D-negative patient receives a D-positive platelet transfusion, 53% of centres would consider treating with Rh immune globulin (RhIg) to prevent alloimmunization in women of childbearing age. Only one centre also gives RhIg to all D-negative patients who are HSCT candidates including adult men and women of no childbearing age., Conclusion: There is wide variation in platelet transfusion practices for supporting D-negative patients. The majority of centres do not have D-positive platelet transfusion policies focused on preventing anti-D alloimmunization specifically in patients undergoing HSCT. Multicentre, longitudinal studies are needed to understand the clinical implications of anti-D alloimmunization in HSCT patients., (© 2020 International Society of Blood Transfusion.)

The AABB recently posted a bulletin (19-02) regarding their recommendations for the use of group O red blood cells (RBCs) during trauma. Though group O Rh(D)-negative RBC units are considered the 'safest', the demand of such units often exceeds the supply. Therefore, O Rh(D)-positive units are often used during the first parts of a massive transfusion protocol (MTP) or patients with particularly severe hemorrhage are switched over from O Rh(D)-negative to O Rh(D)-positive RBC units in order to preserve the O Rh(D)-negative supply. In light of these limitations, it is important to understand the risk of such policies to the patient. The reported risk of alloimmunization after exposure to Rh(D)-positive RBCs ranges widely from 3 to 70%. In response, we performed a retrospective review of 1,198 patients in our institution that had a MTP activation due to trauma. Of those patients, we focused on Rh(D)-negative patients that received at least 1 unit of Rh(D)-positive RBCs. Seventy-two patients met the criteria for inclusion, accounting for 6% of the total population. Of the 72 Rh(D)-negative patients, we identified 17% that formed new Rh group antibodies after exposure to Rh(D)-positive RBCS. All 10 of our alloimmunized patients (two of which were females of childbearing age) formed anti-D, while 3 patients also formed either anti-E or anti-C. Since this was a retrospective review, we did not perform repeated antibody screens for the entire study period, but did review all records for the entire period. We did note that we were more likely to detect an novel alloantibody if more antibody screens were performed during the patient's initial stay and during follow-up visits. We conclude that providing Rh(D) negative patients Rh(D) positive RBC units is not without risk and policies regarding such provisions should be carefully considered. As RBC shortages continue to be a part of daily practice, such issues may continue to be a challenge for the blood bank community., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the risk of inducing RhD immunisation in pregnancies of RhD-negative mothers with an RhD-positive fetus undergoing chorionic villus samplings (CVS) or amniocenteses (AC)., Design, Setting and Population: Registry-based study in a Danish cohort which has not been given rhesus prophylaxis., Methods: Data were retrieved from the Department of Clinical Immunology at Rigshospitalet. All RhD-negative women carrying an RhD-positive fetus with screen test results from weeks 8-12 and weeks 25-29 were linked to data from the Danish Fetal Medicine Database. Data were divided into cases where no invasive prenatal diagnostic procedure was performed, cases that had AC performed, and cases that had CVS performed., Main Outcome Measures: A comparison of the proportion of women who developed RhD immunisation between the two screen tests., Results: The cohort consisted of 10 085 women: 9353 had no invasive procedures performed, 189 had AC and 543 had CVS performed. No women were immunised spontaneously or due to the procedure between the first and second screen test in the group with no procedure performed, or in the AC group. One woman was immunised in the CVS group. When comparing the proportion of women who was immunised in the CVS group with the no invasive test group a non-significant difference was found (P = 0.055)., Conclusion: The RhD immunisation rate before gestational weeks 25-29 in RhD-negative women carrying an RhD-positive fetus is very low, even in women undergoing prenatal invasive testing without rhesus prophylaxis., Tweetable Abstract: The RhD immunisation rate during pregnancy is very low even in women undergoing prenatal invasive testing., (© 2019 Royal College of Obstetricians and Gynaecologists.)

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., (© 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

The mortality from hemorrhage in trauma patients remains high. Early balanced resuscitation improves survival. These truths, balanced with the availability of local resources and our goals for positive regional impact, were the foundation for the development of our prehospital whole blood initiative-using low-titer cold-stored O RhD-positive whole blood. The main concern with use of RhD-positive blood is the potential development of isoimmunization in RhD-negative patients. We used our retrospective massive transfusion protocol (MTP) data to analyze the anticipated risk of this change in practice. In 30 months, of 124 total MTP patients, only one female of childbearing age that received an MTP was RhD-negative. With the risk of isoimmunization very low and the benefit of increased resources for the early administration of balanced resuscitation high, we determined that the utilization of low-titer cold-stored O RhD-positive whole blood would be safe and best serve our community.

Objective: To provide guidelines on use of anti-D prophylaxis to optimize prevention of rhesus (Rh) alloimmunization in Canadian women., Outcomes: Decreased incidence of Rh alloimmunization and minimized practice variation with regards to immunoprophylaxis strategies., Evidence: The Cochrane Library and MEDLINE were searched for English-language articles from 1968 to 200 I, relating to the prevention of Rh alloimmunization. Search terms included: Rho(D) immune globulin, Rh iso- or aile-immunization, anti-D, anti-Rh, WinRho, Rhogam, and pregnancy. Additional publications were identified from the bibliographies of these articles. All study types were reviewed. Randomized controlled trials were considered evidence of highest quality, followed by cohort studies. Key individual studies on which the principal recommendations are based are referenced. Supporting data for each recommendation is briefly summarized with evaluative comments and referenced., Values: The evidence collected was reviewed by the Maternal-Fetal Medicine and Genetics Committees of The Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on the Periodic Health Exam., Recommendations: VALIDATION: These guidelines have been reviewed by the MaternalFetal Medicine Committee and the Genetics Committee, with input from the Rh Program of Nova Scotia. Final approval has been given by the Executive and Council of The Society of Obstetricians and Gynaecologists of Canada., Sponsors: The Society of Obstetricians and Gynaecologists of Canada., (Copyright © 2018. Published by Elsevier Inc.)

Despite the existence of long-standing, well-organized programs for Rh immune globulin (RhIG) prophylaxis, immune anti-D continues to be detected in the D– perinatal population. Between 2006 and 2008, 91 prenatal patients, found to have a previously unidentified anti-D, were followed up with a survey to their treating physician and with additional serologic testing where possible. The physician survey requested pregnancy and RhIG history information, including recent or distant potential alloimmunizing events, and the physicians were asked their opinion on the likely cause for the anti-D. Based on survey responses, updated RhIG information, and results of follow-up serology, anti-D was determined to be attributable to previously unreported RhIG in 44 of 91 (48.3%) cases and to active immunization (immune anti-D) in 36 of 91 cases (39.6%). A probable cause for alloimmunization was reported in 14 of 52 (26.9%) returned surveys. Anti-D alloimmunization continues to occur in our prenatal population despite a comprehensive approach to RhIG therapy. Observations from this prospective patient management strategy include the need for improved application of guidelines for RhIG administration and improved quality of information provided to laboratories assessing RhIG eligibility. A laboratory process for prospective follow-up when unexpected anti-D is detected in pregnancy is recommended.

Background: Recent retrospective studies indicate that D- recipients of D+ apheresis platelets (PLTs) are not alloimmunized to D. Our hospital policy is to offer RhIG to D- women of childbearing age who received D+ apheresis PLTs but not to other D- recipients of D+ apheresis PLTs. We instituted prospective surveillance of the D- recipients who were not given RhIG., Study Design and Methods: All apheresis PLT recipients were prospectively entered into a database that recorded the patient's age, sex, diagnosis, D status, apheresis PLT transfusions, and antibody screen results from before and after PLT transfusions. Data are reported for PLTs transfused between October 16, 2012, and April 16, 2014, and antibody screens obtained through June 16, 2014. The analysis excludes neonates; women not more than 50 years of age; and patients who also received D+ red blood cells, received only D- PLTs, received RhIG, were previously alloimmunized to D, and did not have a follow-up antibody screen after the first D-incompatible apheresis PLT transfusion., Results: A total of 158 of 1107 apheresis PLT recipients were D-. Seventy-nine were eligible for analysis based on the exclusion criteria listed above. None became alloimmunized to D during the observation interval. In 45 (57%) cases the last follow-up antibody screen was obtained at least 4 weeks after the first D-incompatible apheresis PLT transfusion., Conclusion: Prospective surveillance confirms prior retrospective observations that D- patients do not appear to risk D alloimmunization after receiving D+ apheresis PLTs., (© 2014 AABB.)

Rhesus (Rh) antigens are not expressed on platelets but residual red cells carry the risk of anti-D iso-immunization in transfusion recipients of platelet concentrates (PC). The main theoretical risk associated with this reaction relates to female subjects due to potential obstetrical situations of maternal-foetal Rh incompatibility. Isogroup PC transfusion in this system is therefore advised. However, logistical constraints impose frequent Rh-incompatible transfusions that require the recommendation of anti-Rh immunoglobulin in a girl of childbearing age in this situation. This recommendation, already restricted to a group of patients deserves to be questioned over a decade after being issued. Data from published reports are difficult to interpret because of the heterogeneity of the few series (CP type, immune status, timing of biological tests) but the current techniques for preparing products and most common use of CP apheresis limited the risk of immunization. Moreover, platelet transfusions are particularly relevant to immunocompromised populations which, to what extent (heavy chemotherapy and/or hematopoietic stem cells recipients) seems to be protected from this risk. It is noteworthy that the clinical consequences that may be expected from such immunization are not reported. Although some authors emphasize significant isoimmunization rates (maximum 19%), the heterogeneous conditions and the lack of evidence of clinical consequence suggest evaluating the recommendations or revising them towards more targeted indications of seroprophylaxis., (Copyright © 2014. Published by Elsevier SAS.)

Objective: To investigate the clinical characteristics of mirror syndrome., Methods: Retrospective analysis of cases with mirror syndrome. Data of clinical manifestations, laboratory examinations, placental morphology, treatment and prognosis of these patients were obtained and studied., Results: Five cases satisfying the inclusion criteria for mirror syndrome were identified from our hospital database. The incidence of the condition was 0.0154% in China. Mirror syndrome was associated with Rhesus isoimmunization, intrauterine parvovirus B19 infection, fetal neuroblastoma, fetal heart malformation and unknown cause respectively. Fetal symptoms were multi-hydrocele and fetal heart failure complicating fetal hydrops. All of the cases manifested maternal hydrops and hemodilution, the other most common symptoms included hypertension, proteinuria, hypoalbuminemia, anemia, thrombocytopenia and elevated uric acid levels. Fetal outcomes in this study were poor with a perinatal mortality rate of 100%. Placentomegaly was observed in most cases and placental morphology showed villous edema, increased intervillous fibrin deposition and one rare case of fetal adrenal neuroblastoma. Resolution of maternal symptoms was noted within 3-30 days after delivery., Conclusion: Mirror syndrome is associated with a substantially increased risk of fetal death and severe maternal complications. Early diagnosis of this condition during pregnancy is crucial for providing proper treatments and achieving better clinical outcomes.

The prevention of Rhesus D alloimmunization through Rh immune globulin (RhIg) administration is the major indication for the accurate detection and quantification of fetomaternal hemorrhage (FMH). In the setting of D incompatibility, D-positive fetal cells can sensitize the D-negative mother, resulting in maternal anti-D alloantibody production. These anti-D alloantibodies may lead to undesirable sequelae such as hemolytic disease of the newborn (HDN). Since the widespread adoption of FMH screening and RhIg immunoprophylaxis, the overall risk of Rh alloimmunization and infant mortality from HDN has substantially decreased. The rosette screen, the initial test of choice, is highly sensitive in qualitatively detecting 10 mL of fetal whole blood in the maternal circulation. As the screen is reliant on the presence of the D antigen to distinguish fetal from maternal cells, it cannot be used to detect FMH in D-positive mothers or in D-negative mothers carrying a D-negative fetus. The Kleihauer-Betke acid-elution test, the most widely used confirmatory test for quantifying FMH, relies on the principle that fetal RBCs contain mostly fetal hemoglobin (HbF), which is resistant to acid-elution whereas adult hemoglobin is acid-sensitive. Although the Kleihauer-Betke test is inexpensive and requires no special equipment, it lacks standardization and precision, and may not be accurate in conditions with elevated F-cells. Anti-HbF flow cytometry is a promising alternative, although its use is limited by equipment and staffing costs. Hematology analyzers with flow cytometry capabilities may be adapted for fetal cell detection, thus giving clinical laboratories a potentially attractive automated alternative for quantifying FMH., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Etiology of cholestatic liver disease in neonates with hemolytic disease of the newborn (HDN) has been associated with iron overload due to intrauterine red cell transfusions (IUTs). Data on the incidence and severity of cholestasis in neonates with HDN are scarce, and little is known about pathogenesis, risk factors, neonatal management and outcome., Objective: To evaluate incidence, risk factors, management and outcome of cholestasis in neonates with red cell alloimmune hemolytic disease., Methods: All (near-) term neonates with HDN due to red cell alloimmunization admitted to our center between January 2000 and July 2010 were included in this observational study. Liver function tests (including conjugated bilirubin) were routinely performed in the neonatal period. We recorded the presence of cholestasis, investigated several potential risk factors and evaluated the management and outcome in affected neonates., Results: A total of 313 infants with red cell alloimmune hemolytic disease treated with or without IUTs were included. The incidence of cholestasis was 13% (41/313). Two risk factors were independently associated with cholestasis: treatment with at least one IUT (OR 5.81, 95% CI 1.70-19.80, p = 0.005) and rhesus D type of alloimmunization (OR 4.66, 95% CI 1.05-20.57, p = 0.042). Additional diagnostic tests to investigate possible causes of cholestasis were all negative. In 5 infants (12%), supportive medical and nutritional therapy was started, and one neonate required iron chelation therapy., Conclusion: Cholestasis occurs in 13% of neonates with HDN due to red cell alloimmunization, and it is independently associated with IUT treatment and rhesus D type of alloimmunization., (Copyright © 2012 S. Karger AG, Basel.)

Feto-maternal red cell alloimmunization is defined by the presence in a pregnant woman of alloantibodies directed against blood group antigens present on the red blood cells of the fetus and inherited from the father. It arises from the immune response to a first contact to these same antigens during a prior transfusion, transplant or pregnancy. The placental transfer and the fixation of the antibodies on the fetal red cells antigenic targets lead to a haemolysis in the fetus and the newborn. The resulting haemolytic disease can show different clinical forms, from a mild anaemia with neonatal hyperbilirubinemia to a major fetal damage with stillbirth caused by hydrops fetalis. The objective of management strategies of feto-maternal alloimmunization is to detect and monitor maternal alloimmunization and to appreciate the effects on the fetus or the newborn. Since a few years, some new non-invasive techniques of surveillance are used, for instance fetal RHD genotyping on maternal plasma and evaluation of fetal anaemia through velocimetry measurement of the blood flow in the middle cerebral artery. The need for a careful postnatal surveillance has to be emphasized due to the neonatal anaemia, which can be prolonged, and to the resurgence of cases of severe neonatal icteruses recently reported by the Académie de Médecine. The policy of prevention of anti-RH1 alloimmunization should also benefit from the evolution of biological techniques by allowing an improved targeting of concerned women., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The known presence of RHD blood group alleles in apparently D– individuals who are positive for C or E antigens leads to an appropriate investigation for the RHD gene on the red blood cells (RBCs) of D– blood donors, thus preventing their RBCs from immunizing D– recipients. Ready-to-use polymerase chain reaction–sequence-specific primer (PCR-SSP) typing kits are available and allow single-sample results. The need to perform this testing on a large number of donors affiliated with the Transfusion Department of Udine (Northern Italy) led to the use of molecular genetic RH blood group typing with PCR-SSP test kits and DNA samples mixed in pools. From a population of 35,000 blood donors screened for D antigen by serologic typing, a total of 235 samples, distributed in pools of 5 DNA samples, were investigated. Positive results were reevaluated by opening the pools and retesting single samples. Validation of DNA-pool typing with commercial kits was done. Among 235 genotyped samples, 12 were found to be PCR positive (5.1%), exhibiting DEL genotype and RHD-CE-D hybrid alleles. Our data demonstrate that the use of a PCR-SSP commercial test kit with pooled samples is a helpful and valid method to correctly detect RHD alleles. As a consequence, we reclassified our donors as carriers of potentially immunogenic alleles.

Objective: To identify risk factors for Rhesus D (RhD) immunisation in pregnancy, despite adequate antenatal and postnatal anti-D prophylaxis in the previous pregnancy. To generate evidence for improved primary prevention by extra administration of anti-D Ig in the presence of a risk factor., Design: Case-control study., Setting: Nation-wide evaluation of the Dutch antenatal anti-D-prophylaxis programme., Cases: 42 RhD-immunised parae-1, recognised by first-trimester routine red cell antibody screening in their current pregnancy, who received antenatal and postnatal anti-D Ig prophylaxis (gifts of 1000 iu) in their first pregnancy., Controls: 339 parae-1 without red cell antibodies., Methods: Data were collected via obstetric care workers and/or personal interviews with women., Main Outcome Measure: Significant risk factors for RhD immunisation in multivariate analysis., Results: Independent risk factors were non-spontaneous delivery (assisted vaginal delivery or caesarean section) (OR 2.23; 95% CI:1.04-4.74), postmaturity (>or=42 weeks of completed gestation: OR 3.07; 95% CI:1.02-9.02), pregnancy-related red blood cell transfusion (OR 3.51; 95% CI:0.97-12.7 and age (OR 0.89/year; 95% CI:0.80-0.98). In 43% of cases, none of the categorical risk factors was present., Conclusions: In at least half of the failures of anti-D Ig prophylaxis, a condition related to increased fetomaternal haemorrhage (FMH) and/or insufficient anti-D Ig levels was observed. Hence, RhD immunisation may be further reduced by strict compliance to guidelines concerning determination of FMH and accordingly adjusted anti-D Ig prophylaxis, or by routine administration of extra anti-D Ig after a non-spontaneous delivery and/or a complicated or prolonged third stage of labour.

Background: We present the case of a patient with a history of severe combined immunodeficiency (SCID) syndrome successfully treated with bone marrow transplantation. Her resultant Rh alloimmunization complicated her first pregnancy., Case: The patient was diagnosed with SCID syndrome after a series of opportunistic infections. The patient underwent bone marrow transplantation, receiving the graft from her haploidentical father. Once pregnant, her antepartum course was complicated by Rh alloimmunization resulting from her bone marrow transplantation, changing her blood antigen status from D-positive to D-negative. Antenatally, she was closely managed with serial middle cerebral artery Doppler measurements and delivered a healthy baby girl at term., Conclusion: Bone marrow transplantation in a patient with SCID syndrome resulted in Rh isoimmunization, complicating pregnancy management.

Background: Weak D types are thought to express rather quantitative than qualitative D antigen variants. Distinct type-specific phenotypes and weak D cases with anti-D alloimmunization, however, suggest a variable degree of D antigen alteration., Study Design and Methods: Variant D types were investigated by use of molecular typing, RHD sequencing, extended serologic D antigen investigations, and flow cytometric D antigen density determination., Results: Two novel weak D types were discovered, termed weak D type 31 and 32 with single RHD nucleotide substitutions coding for amino acid exchanges in predicted intracellular RhD polypeptide stretches, with antigen densities of approximately 130 and 50 D sites per red blood cell, respectively. Adsorption-elution technique-supported D epitope mapping of these two weak D types, the recently described weak D type 26, and of the most common Central European weak D types (weak D types 1, 2, 3, 4.0, and 4.1) demonstrated the expression of all tested D epitopes. In contrast, a distinct D epitope loss was detected in weak D type 15 and partial D control samples., Conclusion: All novel and prevalent weak D types expressed all tested D epitopes. Our results indicate that adsorption-elution techniques may be of advantage whenever D epitope loss is suspected in extremely weak D variants.

Background: The D antigen of the polymorphic Rh blood group system is of particular clinical importance regarding transfusion- and pregnancy-induced alloimmunization. Different RhD variants with specific clinical implications have been characterized. The least expressed D variants collectively called DEL are serologically detectable only by adsorption-elution techniques, with so far only poorly defined antigenic properties., Study Design and Methods: A comprehensive immunohematologic analysis of five of the six currently known DEL genotypes was performed. DEL phenotypes associated with the RHD(M295I), RHD(IVS3+1g>a), RHD(K409K), RHD(X418L), or RHD(IVS5-38del4) allele were characterized with extended serology and flow cytometry., Results: Epitope mapping with adsorption-elution revealed a prominent D epitope loss in the RHD(IVS3+1g>a)-associated DEL phenotype, whereas in the other four DEL types no signs of qualitative D antigen alteration were detected. The observation of alloanti-D in two RHD(IVS3+1g>a) cases confirmed the partial nature of this DEL phenotype. The RHD(M295I) phenotype exhibited the highest D antigen expression among all investigated DEL types, as determined by a semiquantitative adsorption-elution approach and flow cytometry., Conclusion: In conclusion, evidence is provided that different DEL genotypes code either for partial or complete D antigen expression and that this finding is clinically relevant.

Background: The D antigen includes category D, partial D, and weak D types, which are important because anti-D alloimmunization can occur in some but not all persons that express a variant RHD allele. At present, there is little prospective information on the prevalence of D variants among obstetric patients and potential transfusion recipients., Study Design and Methods: The RHD alleles were prospectively examined in a large patient population identified on the basis of a difference in anti-D reactivity between two reagents., Results: Fifty-five discrepancies (0.96% of D-) were noted among 33,864 ethnically diverse patients over 18 months, of which 54 represented mutated RHD alleles. Seven obstetric patients were assigned D- status based on serology; only 1 patient had a partial RHD allele. Ten of 25 (36%) obstetric patients and 4 of 6 (67%) female potential transfusion recipients of childbearing age or younger were assigned D+ status, and they expressed a D variant known to permit anti-D alloimmunization. In total 20 RHD alleles were identified including category, DVa or DVa-like alleles (n = 7), DAR (n = 8), and four novel RHD alleles including two new DAU alleles., Conclusion: Given the complexity of D antigen expression, it is concluded that some clinically important D variants identified by standard serologic analysis phenotype as D+ and are potentially at risk for the development of anti-D.

Background: Recent molecular studies of the RHD gene have revealed that D(el) individuals retain a grossly intact RHD gene or have a portion of RHD in their genomes. No D(el) phenotype has yet been shown to induce a primary or secondary alloanti-D immunization, however., Case Report: A 67-year-old D- Japanese woman with a history of allosensitization from transfusion of D+ red blood cells (RBCs) was negative for anti-D at admission. After she received RBCs from 19 apparently D- donors, she developed anti-D with an 8-fold titer. The titer of anti-D increased further to 128-fold after transfusions of cross-match-compatible D- negative RBCs from 40 donors over the next 2 years. Two of 59 donors were found to be RHD gene-positive and antigen D- with a D(el) phenotype, that is, RHD(K409K)., Conclusion: This is the first case in which RBCs having the D(el) phenotype induced a secondary alloanti-D immunization. A D- donor with the RHD(K409K) allele was associated with the development of anti-D. Adverse episodes or evidence of hemolysis was not observed after the transfusion of RHD(K409K) RBCs. Further clinical evidence is needed to reveal whether the D(el) phenotype has a clinically relevant potential for anti-D immunization.

Introduction: Guidelines for distribution and use of blood products have been established for both blood transfusion institution and hospitals, in particular for the use of Rh (D)-incompatible platelet concentrates. The aim of this study was to evaluate: 1) the rate of attribution for the Rh (D)-incompatible platelets concentrates, 2) the immunisation prophylaxis practices, 3) the immunological consequences using short and medium term follow-up of transfused patients., Methods: Patients with Rh (D)-incompatible platelets concentrate administered during the year 2003 at Rouen University Hospital were retrospectively selected. Patients on transfusion were described. The relationship of various factors with the injection as well as the appearance of allo-immunization was statistically tested., Results: During a year, 280 Rh (D)-incompatible platelets concentrates were administered to 67 patients. Immunisation prophylaxis by injection of Ig anti-D was not systematically performed. Four immunizations in the Rhesus group system were identified: 2 against D antigen (Ag), 1 against E Ag and 1 against C Ag. Immunisations against D Ag occurred for two younger women considered as immunodeficient. Immunization prophylaxis was more frequent in poly-transfused patients. However no difference was observed for the other factors., Conclusion: Compatibility concerning Rhesus (D) is not always possible. The immunization against red cells persists, in particular against the antigens of the Rhesus group system and moreover for the immunodeficient patients. Recommendations for immunization prophylaxis by injection of specific anti-D immune-globulin (Ig) could be reconsidered.

Blood transfusion in patients with sickle cell disease (SCD) is limited by the development of alloantibodies to erythrocytes. In the present study, the frequency and risk factors for alloimmunization were determined. Transfusion records and medical charts of 828 SCD patients who had been transfused and followed at the Belo Horizonte Blood Center, Belo Horizonte, MG, Brazil, were retrospectively reviewed. Alloimmunization frequency was 9.9% (95% CI: 7.9 to 11.9%) and 125 alloantibodies were detected, 79% of which belonged to the Rhesus and Kell systems. Female patients developed alloimmunization more frequently (P = 0.03). The median age of the alloimmunized group was 23.3 years, compared to 14.6 years for the non-alloimmunized group (P < 0.0001). Multivariate analyses were applied to the data for 608 hemoglobin (Hb) SS or SC patients whose number of transfusions was recorded accurately. Number of transfusions (P = 0.00006), older age (P = 0.056) and Hb SC (P = 0.02) showed independent statistical associations with alloimmunization. Hb SC patients older than 14 years faced a 2.8-fold higher (95% CI: 1.3 to 6.0) risk of alloimmunization than Hb SS patients. Female Hb SC patients had the highest risk of developing alloantibodies. In patients younger than 14 years, only the number of transfusions was significant. We conclude that an increased risk of alloimmunization was associated with older patients with Hb SC, specially females, even after adjustments were made for the number of transfusions received, the most significant variable.

Fetomaternal hemorrhage (FMH) is a common obstetrical occurrence most often associated with small volumes of blood transferred across the placenta. Fetomaternal hemorrhage leads to alloimmunization of Rh D-negative mothers, resulting in an increased risk of hemolytic disease of the newborn. Massive FMH involving volumes of blood greater than 30 mL can cause substantial fetal morbidity and mortality. Massive FMH may present with signs and symptoms such as decreased movement, sinusoidal heart rhythms, or fetal anomalies. We present 3 cases of clinically unexpected massive FMH of 206, 88, and 155 mL. The treating clinicians were unaware of any fetal or maternal signs or symptoms of FMH until contacted by the laboratory. These cases illustrate the necessity for FMH quantitation, even in the absence of clinical suspicion. Additional studies are needed to find better ways to identify these patients in advance. Development of criteria allowing identification of patients at risk would be of benefit to both mother and baby.

Background: Thalassemia major is a common hemoglobinopathy in the Arabian Gulf region. However, limited data are available on the frequency of RBC alloimmunization and autoimmunization in transfusion-dependent Arab thalassemia patients., Study Design and Methods: A total of 190 thalassemia major patients were classified as Kuwaiti Arab and non-Kuwaiti Arab. Pretransfusion investigation records were reviewed for the presence of RBC alloantibody and autoantibody, and the age at which RBC alloantibody was developed., Results: Fifty-seven (30%) patients developed RBC alloantibodies. The most common clinically significant alloantibodies were directed against antigens in the Kell and Rh systems. Anti-K developed in 41 (72%) patients followed by anti-E in 26 (45.6%). RBC autoantibodies developed in 21 (11%) patients with and without underlying RBC alloantibodies. Sixty-six (49.6%) RBC alloantibodies developed between the ages of 2 and 10 years., Conclusion: Several factors might have contributed to the high alloimmunization and autoimmunization rate observed in this study, including the heterogeneity of the population living in Kuwait, lack of better-matched donors for those patients, and the use of poststorage leukodepleted blood. It is recommended that thalassemia patients receive blood matched for Rh and Kell antigens and prestorage leukodepleted RBCs.

To improve routine D typing and define transfusion strategy, it is important to establish the frequency of partial D alleles and their susceptibility to anti-D alloimmunization due to transfusion or pregnancy. We identified the partial D DNB that was caused by an RHD(G355S) allele associated with a CDe haplotype and whose phenotype presented a normal D in routine typing. The antigen density was about 6000 D antigens per red blood cell, and the Rhesus index was 0.02. Five anti-D immunization events with allo-anti-D titers up to 128 were observed. Twelve carriers of DNB were whites of Central Europe; the only Danish proband had Austrian ancestry. DNB was the most frequent partial D recognized so far in whites, occurring with frequencies of up to 1:292 in Switzerland. DNB was the underlying partial D phenotype in a relevant fraction of anti-D immunizations occurring in whites.

In pregnant women subject to abdominal trauma or other foetomaternal haemorrhage, foetal red blood cells containing haemoglobin-F (HbF) can be found in the circulation. Recently, a monoclonal antibody to HbF has become commercially available, enabling application of a flow cytometric immunofluorescence method for accurately determining the concentration of HbF+ red blood cells. We demonstrate that white blood cells are included in the cluster selected as red blood cells and that these white blood cells exhibit a level of autofluorescence that coincides with the fluorescence signal from HbF+ red blood cells. However, these white blood cells can be excluded from the analysis, thus preventing spuriously increased HbF+ red blood cell counts. We present the results of patient samples containing HbF+ red cells as illustrations of the technique and as a potential interference by HbF-containing cells of nonfoetal origin. Using samples spiked with cord blood, the method is exactly linear with a high coefficient of correlation (r=0.997). Furthermore, the assay has excellent precision (CV < 2.4%), a low limit of detection (0.12% HbF+ RBC), is independent of Rhesus D and can be completed within 1.5 h. This method is suitable for accurate determination of foetomaternal haemorrhage.

Paediatric transfusion encompasses a wide range of clinical circumstances including the consideration of maternal antibodies, the changing nature of the transfusion recipient with respect to growth and development, and the management of inherited conditions which if optimally treated in early life may have problems which are delayed or less severe in adult life. Whilst the transfusion of adults and children has much in common, a child cannot be considered as a scaled down adult; there are many important differences. Developmental changes are most marked in the neonate and, together with the fact that their antibodies are maternally derived, this population provide some of the most striking challenges. The increased use of intra uterine transfusion adds an extra dimension here. A particular paediatric concern is the long-term consequences of transfusion. It is to be hoped that paediatric transfusion recipients will live long enough that any potential problems will manifest themselves, thus the aim must be to minimize transfusion risks.

This work was carried out in Ramadi, Iraq over the period 1993 to 1997. Of 487 rhesus (Rh)-negative mothers tested and followed up, 172 were primigravida, 1.7% of whom were Rh-isoimmunized. The frequency of isoimmunization increased with increasing number of pregnancies (4.9% for second pregnancies to 45.4% for fifth pregnancies). Comparison of our results with other earlier studies shows that the incidence of Rh-isoimmunization in our study was considerably greater than the others.

Intravenous drug abuse is a risk for alloimmunization in pregnancy. One case is presented of a nulliparous Rhesus-negative parturient who shared her Rhesus-positive partner's needles for the injection of heroin; she subsequently developed elevated antepartum anti-D titers despite routine anti-D prophylaxis.

Background: Maternal sensitization with rhesus anti-C antibodies is comparatively rare and usually benign. In pregnancies conceived using donor oocytes, the mother's blood group may differ from that of both the father and the oocyte donor, making blood group incompatibility more likely., Case: Twins, the result of a surrogate pregnancy using donor oocytes, were born with severe hemolytic disease due to rhesus anti-C antibodies. Both infants required exchange transfusion for profound anemia at birth. Isoimmunization in the surrogate mother was not detected antenatally. The twins were delivered by emergency cesarean section due to fetal compromise, detected fortuitously when the mother attended for routine fetal assessment at 35 weeks' gestation., Conclusion: Isoimmunization with anti-C antibodies is not always benign and may cause significant hemolytic disease. With the success of in vitro fertilization and oocyte donation, more infertile couples may use these methods to conceive, with or without surrogacy arrangements. In such cases, the provision of antenatal care may become a complex matter, involving several parties, and good communication between everyone involved is vital. In pregnancies conceived with donor oocytes, there may be a higher risk of blood group incompatibility, and special vigilance is warranted.

Objective: To determine the likely factors that contribute to RhD sensitisation., Design: Retrospective study of all new cases of RhD sensitisation occurring between 1988 and 1991., Setting: Leeds Blood Centre, National Blood Service, Yorkshire., Population: One hundred and forty-seven cases of RhD sensitisation from 15 obstetric units within the Yorkshire region, of which 129 (312 pregnancies) could be assessed., Main Outcome Measure: S Identification of potential immunising events and adherence with recommendations on anti-D immunoglobulin administration., Results: Twenty-eight women (22%) had immune anti-D antibodies during their first pregnancy or at delivery and 50 (39%) in their second pregnancy. Overall, 98 potential immunising events were identified in 62 women, excluding delivery; 67 women (52%) had no events, other than delivery. Miscarriages and medical terminations of pregnancy accounted for 81% of all identified events. Iatrogenic failure to adhere to recommendations for the administration of anti-D immunoglobulin occurred in a significant proportion of women who subsequently developed immune anti-D antibodies. Anti-D immunoglobulin failed to protect against immunisation despite adherence to the protocol in 20 events (20%), 13 of which involved miscarriages or termination of pregnancy < 20 weeks of gestation. Potentially, antenatal prophylaxis might have prevented 86% of immunisations that were identified during the first pregnancy., Conclusions: The introduction of antenatal administration of anti-D immunoglobulin could significantly reduce the level of sensitisation in primigravidae, and adherence to recommendations for administration of anti-D immunoglobulin could be improved. Consideration should be given to reviewing the current recommendation that a dose of 250 IU of anti-D immunoglobulin is adequate following termination of pregnancy before a gestational age of 20 weeks.

Plasmapheresis, ultrafiltration of blood, and hemodialysis were effectively used in the treatment of a 20-year-old woman after cesarean section who was transfused 300 ml of wrong group blood. The resultant hemotransfusion conflict was characterized by shock, disseminated intravascular coagulation, hemolysis, acute pulmonary edema and renal failure. Plasmapheresis helped abolish the hemolysis. Pulmonary edema was eliminated by ultrafiltration of 2 liters of blood. Six sessions of hemodialysis administered within 10 days arrested renal insufficiency. The treatment administered may be considered as the method of choice in such patients.

The incidence of antepartum Rh isoimmunization has been limited by third-trimester Rh immune globulin (RhIg) administration. Prophylactic failures are uncommon but can occur if sensitization takes place prior to the 28th week of gestation. We report a case of midtrimester Rh sensitization in an anticardiolipin antibody-positive primipara coincident with the discovery of an elevated maternal serum alpha-fetoprotein value, oligohydramnios and fetal growth retardation. This case suggests that fetal-maternal hemorrhage and subsequent sensitization may be facilitated by anticardiolipin antibody-induced placental damage. Prophylactic midtrimester RhIg administration might avoid sensitization in similar cases.

Objective: To identify the reasons behind failures to prevent the development of Rhesus (D) haemolytic disease of the newborn., Design: Retrospective analysis of the case records of all pregnancies that resulted in the birth of an infant with a positive direct antiglobulin test on the cord red cells born to Rh(D) negative women between 1 April 1985 and 31 March 1990., Setting: Obstetric units in the South East Scotland region and the South East Scotland Regional Blood Transfusion Service Antenatal Laboratory., Main Outcome Measures: The causes and clinical consequences of maternal immunisation to the Rhesus (D) antigen., Results: Between 1985 and 1990, 80 pregnancies resulted in the birth of an infant sensitised with anti-D on the cord red cells. There were no deaths due to haemolytic disease, but considerable resources were deployed in obstetric and neonatal care for these pregnancies. Sufficient data were available to categorise the cause of maternal immunisation in 70 pregnancies. Seven cases were due to immunisation by pregnancy before 1970. Sixty-three cases could be attributed to failure of the Rhesus programme: 10 cases (16%) were due to failure to implement the programme adequately, the other 53 cases (84%) were due to failure of the current guidelines to provide adequate protection. Late immunisation in an uncomplicated pregnancy was the single commonest identifiable cause., Conclusions: It is likely that substantial further reductions in Rhesus (D) immunisation and haemolytic disease of the newborn will require changes in the Rhesus prevention programme. In particular the role of antenatal prophylaxis requires detailed consideration.

Unlabelled: Mutations within the genetic Rh system can produce partial deletions of one or more epitope of the D antigen, known as incomplete D. These people, classified Rh positive, are capable of producing anti-D antibodies when exposed to D positive red blood cells (rbcs). We describe the study of a Rh positive, 34 year old, spanish-indian ("mestiza") female patient, in whose blood anti-D antibodies were detected after a blood transfusions. The results of the tests showed a partial deletion of the D antigen in the patient and three of her family members., Patients and Methods: The following tests were done to the patient and her family members: 1) ABO and Rh typing; 2) Direct antiglobulin test; 3) Detection of irregular antibodies in their blood serum; 4) Rh genotype; 5) Cross matching of the patient's serum with rbcs of her Rh positive relatives; 6) Titration of a monoclonal anti-D (IgM) and a polyclonal anti-D (IgG) of human origin with the patient's rbcs and with Rh positive rbcs of her family members whose erythrocytes didn't react with the patient's serum; 7) Measurement of the antigenic density of the D antigen by flow cytometry (indirect immunofluorescence) in the rbcs of the patient and in those family members who had the defect, using a polyclonal anti-D (IgG)., Results: 1) An anti-D antibody which didn't react with its own Rh positive rbcs was found in the patient's serum; 2) This antibody didn't react with the Rh positive rbcs of her father and two out of her 4 brothers; 3) The cytometric study of these cells (R)r) showed a immunofluorescence pattern weaker than the control cells of the same genotype, but with a variable expression between 15 to 41%., Conclusions: The study showed: 1) The presence of an anti-D antibody in a Rh positive patient who had been previously sensitized (by blood transfusion); 2) This antibody was able to react with Rh positive rbcs but not with those of the patient and her family members who had the same partial deletion; 3) The defect was transmitted heterozygously, with a high degree of penetration, but with variable expression; 4) A low antigenic density for her D antigen by flow cytometry.