Anti-D immunization after D positive platelet transfusions in D negative recipients: A systematic review and meta-analysis.

BACKGROUND: Anti-D can be formed after D-incompatible platelet transfusions due to contaminating D+ red blood cells. These antibodies are of particular importance in women of childbearing potential, because anti-D is most often involved in severe cases of hemolytic disease of the fetus and newborn. This systematic review determined the frequency of anti-D after D+ platelet transfusions and risk factors for D alloimmunization. STUDY DESIGN AND METHODS: Relevant literature was searched using PubMed, Embase and Web of Science until December 2022. Overall anti-D frequency and risk factors were estimated using a random effects meta-analysis. RESULTS: In 22 studies, a total of 3028 D- patients received a mean of six D+ platelet transfusions. After a mean follow-up of seven months 106 of 2808 eligible patients formed anti-D. The pooled anti-D frequency was 3.3% (95% CI 2.0-5.0%; I2 71%). After including only patients with an undoubtable follow-up of at least 4 weeks, 29 of 1497 patients formed anti-D with a pooled primary anti-D rate of 1.9% (95% CI 0.9-3.2%, I2 44%). Women and patients receiving whole blood derived platelets had two and five times higher anti-D rates compared with men and patients receiving apheresis derived platelets, respectively. DISCUSSION: Anti-D immunization is low after D incompatible platelet transfusions and dependent on recipients' sex and platelet source. We propose anti-D prophylaxis in girls and women, capable of becoming pregnant in the future, that received D+ platelets, regardless of platelet source, to reduce the risk of anti-D induced hemolytic disease of the fetus and newborn.

Rh immune globulin immunoprophylaxis after RhD-positive red cell exposure in RhD-negative patients via transfusion: A survey of practices.

BACKGROUND: Current Association for the Advancement of Blood & Biotherapies (AABB) standards require transfusion services to have a policy on Rh immune globulin (RhIG) immunoprophylaxis for when RhD-negative patients are exposed to RhD-positive red cells. This is a survey of AABB-accredited transfusion services in the United States (US) regarding institutional policies and practices on RhIG immunoprophylaxis after RhD-negative patients receive RhD-positive (i.e., RhD-incompatible) packed red blood cell (pRBC) and platelet transfusions. RESULTS: Approximately half of the respondents (50.4%, 116/230) have policies on RhIG administration after RhD-incompatible pRBC and platelet transfusions, while others had policies for only pRBC (13.5%, 31/230) or only platelet (17.8%, 41/230) transfusions, but not both. In contrast, 18.3% (42/230) report that their institution has no written policies on RhIG immunoprophylaxis after RhD-incompatible transfusions. Most institutions (70.2%, 99/141) do not have policies addressing safety parameters to mitigate the risk of hemolysis associated with the high dose of RhIG required to prevent RhD alloimmunization after RhD-incompatible pRBC transfusions. DISCUSSION: With approximately half of US AABB-accredited institutions report having policies on RhIG immunoprophylaxis after both RhD-incompatible pRBC and platelet transfusions, some institutions may not be in compliance with AABB standards. Further, most with policies on RhIG immunoprophylaxis after RhD-incompatible pRBC transfusion do not have written safeguards to mitigate the risk of hemolysis associated with the high dose of RhIG required. CONCLUSION: This survey underscores the diverse and inadequate institutional policies on RhIG immunoprophylaxis after RhD exposure in Rh-negative patients via transfusion. This observation identifies an opportunity to improve transfusion safety.

40 years of researching the Del phenotype results in a change of transfusion practice.

Anti-D cannot agglutinate red cells of any Del phenotype in routine serology. Many individuals with East Asian ancestry who type D-negative in serology harbor a Del phenotype. Almost all such individuals carry one distinct DEL variant, dubbed Asian-type DEL, known as RHD*01EL.01, RHD*DEL1, RHD:c.1227G>A, formerly known as RHD(K409K). Clinical evidence strongly suggests that Asian-type DEL individuals can safely be transfused with RhD-positive blood and do not need anti-D prophylaxis in pregnancy.

Receipt of RhD-positive whole blood for life-threatening bleeding in female children: A survey in alloimmunized mothers regarding minimum acceptable survival benefit relative to risk of maternal alloimmunization to anti-D.

BACKGROUND: Low-titer group O whole blood (LTOWB) for treatment of hemorrhagic shock sometimes necessitates transfusion of RhD-positive units due to short supply of RhD-negative LTOWB. Practitioners must choose between using RhD-positive LTOWB when RhD-negative is unavailable against the risk to a female of childbearing potential of becoming RhD-alloimmunized, risking hemolytic disease of the fetus and newborn (HDFN) in future children, or using component therapy with RhD-negative red cells. This survey asked females with a history of red blood cell (RBC) alloimmunization about their risk tolerance of RhD alloimmunization compared to the potential for improved survival following transfusion of RhD-positive blood for an injured RhD negative female child. STUDY DESIGN AND METHODS: A survey was administered to RBC alloimmunized mothers. Respondents were eligible if they were living in the United States with at least one red cell antibody known to cause HDFN and if they had at least one RBC alloimmunized pregnancy. RESULTS: Responses from 107 RBC alloimmmunized females were analyzed. There were 32/107 (30%) with a history of severe HDFN; 12/107 (11%) had a history of fetal or neonatal loss due to HDFN. The median (interquartile range) absolute improvement in survival at which the respondents would accept RhD-positive transfusions for a female child was 4% (1%-14%). This was not different between females with and without a history of severe or fatal HDFN (p = .08 and 0.38, respectively). CONCLUSION: Alloimmunized mothers would accept the risk of D-alloimmunization in a RhD-negative female child for improved survival in cases of life-threatening bleeding.

Incidence of formation of anti-D between patients with and without a history of solid organ transplant.

BACKGROUND AND OBJECTIVES: Solid organ transplant surgeries including liver transplants constitute a substantial risk of bleeding complications and given frequent national blood shortages, supporting D-negative transplant recipients with D-negative red blood cell products perioperatively can be difficult for the transfusion services. This study was designed to compare the incidence of alloimmunization after D-mismatched red cell transfusions between patients with and without a history of solid organ transplant at a single tertiary care hospital. The patients undergoing solid organ transplants are on strong immunosuppressive regimens perioperatively to help reduce the risk of rejection. We hypothesized that the use of these immunosuppressive agents makes these patients very less likely to mount an immune response and form anti-D antibodies when exposed to the D-positive red blood cell products perioperatively. STUDY DESIGN AND METHODS: At our center, D-negative patients who received ≥1 unit of D-positive red blood cell products were identified using historical transfusion records. Antibody testing results were examined to determine the incidence of the formation of anti-D and any other red cell alloantibodies after transfusion and these results were compared between patients with and without a history of solid organ transplant. RESULTS: We were able to identify a total of 22 patients over 10 years with D-negative phenotype who had undergone a solid organ transplant and had received D-positive red blood cell products during the transplant surgeries. We also identified a second group of 54 patients with D-negative phenotype who had received D-positive red blood cell products for other indications including medical and surgical. A comparison of the data showed no new anti-D formation among patients with a history of D mismatched transfusion during solid organ transplant surgeries. CONCLUSION: Among our limited study population, we observed a very low likelihood of D alloimmunization among solid organ transplant recipients. A larger, prospective study could help further evaluate the need for prophylactic D matching for red cell transfusions during solid organ transplant surgeries.

Does high body mass index (>25 kg/m2) or weight (>80 kg) reduce the effectiveness of anti-D prophylaxis in Rh(D)-negative pregnant women? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haemolytic disease of the foetus and newborn (HDFN) occurs when maternal antibodies, often triggered by foetal antigens, destroy foetal and neonatal red blood cells. Factors like antibody strength, quantity and gestational age influence HDFN severity. Routine antenatal anti-D prophylaxis (RAADP) has significantly reduced HDFN cases. However, the effect of overweight/obesity (body mass index [BMI] > 25/30 kg/m2) on anti-D prophylaxis efficacy remains unclear. This systematic review will examine the impact of BMI on anti D prophylaxis effectiveness in Rh(D) negative pregnant women. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. We searched databases from 1996 to 2023, focusing on studies exploring the link between high BMI/weight and anti-D serum levels in Rh(D)-negative pregnant women with Rh(D)-positive foetuses. Ten eligible studies were included, three suitable for meta-analysis. Study quality was assessed using the Strengthening the Reporting Observation Studies in Epidemiology (STROBE) checklist. Statistical analyses included Pearson correlation coefficients and risk differences. RESULTS: Our meta-analysis revealed a significant negative correlation (r = -0.59, 95% confidence interval [CI]: -0.83 to -0.35, p = 0.007) between high BMI/weight and serial anti-D levels in in Rh(D)-negative pregnant women with Rh(D)-positive foetuses. High BMI/weight had lower odds of serial anti-D level exceeding 30 ng/mL (arcsine risk difference [ARD] = 0.376, 95% CI: 0.143-0.610, p = 0.002). Heterogeneity among studies was low (I2 = 0). CONCLUSION: While our analysis suggests a potential linkage between high BMI/weight and reduced efficacy of anti-D prophylaxis, caution is warranted due to study limitations. Variability in study design and confounding factors necessitate careful interpretation. Further research is needed to confirm these findings and refine clinical recommendations.

Why do RhD negative pregnant women still become anti-D immunized despite prophylaxis with anti-D immunoglobulin?

Maternal allo-anti-D in RhD negative pregnant women may cause mild to severe hemolytic disease of the fetus and newborn. Although several other antibodies may also destroy red blood cells of the fetus and newborn, preventive measures with anti-D immunoglobulin are only available for D antigen. Targeted antenatal care together with postpartum prophylaxis with anti-D immunoglobulin has significantly reduced the D-alloimmunization risk. Potentially sensitizing events like trauma to the pregnant abdomen, vaginal bleeding, and amniocentesis may lead to fetomaternal hemorrhage and necessitate additional doses. Despite comprehensive programs with these targeted measures, allo-anti-D is still the most common reason for severe hemolytic disease of the fetus and newborn. Where do we fail then? Here, in this review, I would therefore like to discuss the reasons for D-alloimmunizations hoping that the greater focus will pave the way for further reduction in the number of pregnancy-related allo-anti-Ds.

'Old is gold' does conventional test tube method still reign supreme? An immuno-haematological survey of anti-D detection and titration in ante-natal cases among major hospitals across India.

INTRODUCTION: Anti-D detection and titration plays a major role in RhD negative antenatal cases both, for monitoring maternal as well as fetal status as well as initiation of early therapeutic interventions, such as intra-uterine transfusions (IUT) to improve maternal as well as fetal morbidity and mortality and reduce the adverse effects of haemolytic disease of fetus and newborn (HDFN). We conducted a survey focusing on the policies and procedures of anti-D detection and titration among major tertiary care centres across India. METHODOLOGY: The survey was drafted by a working group of transfusion medicine and immunohematology specialists from six different centres in India. Data were obtained via the use of an online questionnaire. RESULTS: Results were categorised into four categories, Hospital information, immuno-haematological testing methodology, clinical significance of anti-D testing and the role of transfusion medicine specialists. The survey highlighted the modalities as well as the methodologies of anti-D detection and titration in antenatal women across different major tertiary care centres in India. CONCLUSION: This survey provided a unique snapshot of the prevalent methodologies being employed by major tertiary care centres across the country for detection and titration of anti-D levels as well as the important role it plays in the therapy of affected antenatal women to minimise adverse effects on the fetus.

Serologic profiling of D variants in donor routine: unveiling the impact on false-negative results and alloimmunization.

The high number of D variants can lead to the unnecessary use of Rh immune globulin, overuse of D- RBC units, and anti-D allommunization. D variant prevalence varies among ethnic groups, and knowledge of the main variants present in a specific population, their behavior in serologic tests, and their impact on clinical practice is crucial to define the best serologic tests for routine use. The present study aimed to explore the serologic profile of D variants and to determine which variants are most associated with false-negative D typing results and alloimmunization. Donor samples were selected in two study periods. During the first period, D typing was performed on a semi-automated instrument in microplates, and weak D tests were conducted in tube or gel tests. In the second period, D typing was carried out using an automated instrument with microplates, and weak D tests were performed in solid phase. Samples from patients typed as D+ with anti-D were also selected. All samples were characterized by molecular testing. A total of 37 RHD variants were identified. Discrepancies and atypical reactivity without anti-D formation were observed in 83.4 percent of the samples, discrepant D typing results between donations were seen in 12.3 percent, and D+ patients with anti-D comprised 4.3 percent. DAR1.2 was the most prevalent variant. Weak D type 38 was responsible for 75 percent of discrepant samples, followed by weak D type 11, predominantly detected by solid phase. Among the D variants related to alloimmunization, DIVa was the most prevalent, which was not recognized by serologic testing; the same was true for DIIIc. The results highlight the importance of selecting tests for donor screening capable of detecting weak D types 38 and 11, especially in populations where these variants are more prevalent. In pre-transfusion testing, it is crucial that D typing reagents demonstrate weak reactivity with DAR variants; having a serologic strategy to recognize DIVa and DIIIc is also valuable.

Antenatal RHD screening to guide antenatal anti-D immunoprophylaxis in non-immunized D- pregnant women.

In pregnancy, D- pregnant women may be at risk of becoming immunized against D when carrying a D+ fetus, which may eventually lead to hemolytic disease of the fetus and newborn. Administrating antenatal and postnatal anti-D immunoglobulin prophylaxis decreases the risk of immunization substantially. Noninvasive fetal RHD genotyping, based on testing cell-free DNA extracted from maternal plasma, offers a reliable tool to predict the fetal RhD phenotype during pregnancy. Used as a screening program, antenatal RHD screening can guide the administration of antenatal prophylaxis in non-immunized D- pregnant women so that unnecessary prophylaxis is avoided in those women who carry a D- fetus. In Europe, antenatal RHD screening programs have been running since 2009, demonstrating high test accuracies and program feasibility. In this review, an overview is provided of current state-of-the-art antenatal RHD screening, which includes discussions on the rationale for its implementation, methodology, detection strategies, and test performance. The performance of antenatal RHD screening in a routine setting is characterized by high accuracy, with a high diagnostic sensitivity of ≥99.9 percent. The result of using antenatal RHD screening is that 97-99 percent of the women who carry a D- fetus avoid unnecessary prophylaxis. As such, this activity contributes to avoiding unnecessary treatment and saves valuable anti-D immunoglobulin, which has a shortage worldwide. The main challenges for a reliable noninvasive fetal RHD genotyping assay are low cell-free DNA levels, the genetics of the Rh blood group system, and choosing an appropriate detection strategy for an admixed population. In many parts of the world, however, the main challenge is to improve the basic care for D- pregnant women.

Intramuscular Anti-D treatment for immune thrombocytopenia: A single centre experience.

Intravenous Anti-Rhesus-D immunoglobulin (Anti-D) is a first-line treatment option for immune thrombocytopenia in non-splenectomised and RhD-positive patients. In this report, we retrospectively review our experience with intramuscular (IM) Anti-D treatment in 74 adult patients between 1990 and 2018. We found that 73% of patients showed a response; almost all of them had complete responses (68.9%), and 26% achieved complete responses sustained at least 6 months after treatment discontinuation. [Correction added on 02 December 2022, after first online publication: In the preceding sentence, '(68.89%)' has been corrected to '(68.9%)' in this version.] No significant side effects were observed with no cases of acute haemolysis or anaemia reported. We conclude from this study that IM Anti-D is an effective and safe treatment for immune thrombocytopenia.

Asian-type DEL (RHD*DEL1) with an allo-anti-D: A paradoxical observation in a healthy multiparous woman.

BACKGROUND: The DEL phenotype is the D variant expressing the least amounts of D antigen per red cell. Asian-type DEL (RHD:c:1227G > A) is the most prevalent DEL in East Asia without any anti-D alloimmunization reported before. We investigated the first observation of an anti-D in any DEL phenotype, reported in the Japanese language at a 1987 conference, only 3 years after the discovery of DEL. METHODS: We contacted the proband 35 years after the initial report. Standard hemagglutination, adsorption/elution, and flow cytometry tests were performed, as was nucleotide sequencing for the RHD, RHCE, and HLA class I and class II genes. RESULTS: The healthy multiparous Japanese woman, a regular blood donor, still had the anti-D of titer 8 representing an alloantibody by standard serologic methods. Unexpectedly, she carried an Asian-type DEL without any additional RHD gene variation. All 12 HLA alleles identified were known in the Japanese population. Interestingly, one of her HLA-DRB1 and a variant of her HLA-DQB1 alleles had previously been associated with anti-D immunization. CONCLUSION: We described an allo-anti-D, maintained for more than three decades, in an Asian-type DEL. The combination of two implicated HLA alleles were rare and could have contributed to the anti-D immunization. Continued monitoring of anti-D immunization events in patients with DEL is warranted, and we discuss possible mechanisms for further study. As only this single observation has been recognized in the last 35 years, the current recommendation is affirmed: Individuals with Asian-type DEL should be treated as Rh D-positive for transfusion and Rh immune prophylaxis purposes.

Association of HLA-DRB1 alleles with anti-D alloimmunization in RhD negative pregnant women in India.

BACKGROUND: Human leukocyte antigen (HLA) restriction plays an important role in the susceptibility to alloimmunization against red blood cell (RBC) antigens. The prevalence of anti-D alloimmunization in RhD negative pregnancy is still quite high in our population. Thus, we planned this study to determine the association of HLA-DRB1 alleles with anti-D alloimmunization in RhD negative pregnant women. MATERIAL AND METHODS: RBC antibody screen (ABS) was performed for RhD negative pregnant women attending the antenatal clinic our institute. Those with a negative result were included in the 'non-alloimmunized' (NAL) group ('Control' group), while those with anti-D alloantibody on performing antibody identification were included in the alloimmunized (AL) group of the study (n = 50 each). ABS and identification were done using column agglutination technique. The HLA-DRB1 typing was done by Luminex based reverse sequence specific oligonucleotide probing (SSOP) using commercial kits. The HLA-DRB1 allele frequency was compared in both the groups. RESULTS: There was a significant difference between the two groups in terms of gravida (p < 0.001) and history of anti-D immunoprophylaxis (p < 0.001). The frequency of HLA-DRB1*03 and HLA-DRB1*04 alleles was significantly higher in the AL group than the NAL group: 40 % versus 18 % [Odds Ratio (OR): 3.04, 95 % CI: 1.21-7.6; p = 0.015] for HLA-DRB1*03 alleles and 18 % versus 4 % (OR: 5.27, 95 % CI: 1.08-25.78, p = 0.025) for HLA-DRB1*04 alleles. CONCLUSION: The frequency of HLADRB1*03 and HLADRB1*04 alleles was significantly higher in RhD negative pregnant women alloimmunized with anti-D alloantibody.

Rate of D-alloimmunization in trauma does not depend on the number of RhD-positive units transfused: The BEST collaborative study.

BACKGROUND: Evidence indicates the life-saving benefits of early blood product transfusion in severe trauma resuscitation. Many of these products will be RhD-positive, so understanding the D-alloimmunization rate is important. METHODS: This was a multicenter, retrospective study whereby injured RhD-negative patients between 18-50 years of age who received at least one unit of RhD-positive red blood cells (RBC) or low titer group O whole blood (LTOWB) during their resuscitation between 1 January, 2010 through 31 December, 2019 were identified. If an antibody detection test was performed ≥14 days after the index RhD-positive transfusion then basic demographic information was collected, including whether the patient became D-alloimmunized. The overall D-alloimmunization rate, and the rate stratified by the number of units transfused, were calculated. RESULTS: Data were collected from nine institutions. Five institutions reported fewer than 10 eligible patients each and were excluded. From the remaining four institutions, all from the USA, there were 235 eligible patients; 77 (random effects estimate: 32.7%; 95% CI: 19.1-50.1%) became D-alloimmunized. Three of the institutions reported D-alloimmunization rates ≥38.6%, while the remaining institution's rate was 12.2%. In both random and fixed-effects models, the rate of D-alloimmunization was not significantly different between those who received one RhD-positive unit and those who received multiple RhD-positive units. CONCLUSION: In this large, multicenter study of injured patients, the overall rate of D-alloimmunization fell within the range previously reported. The rate of D-alloimmunization did not increase as the number of transfused RhD-positive units increased. These data can help to inform RhD type selection decisions.

Real-world experience of anti-D immunoglobulin in immune thrombocytopenia.

In developing countries, anti-D has been used in immune thrombocytopenia (ITP) as a cheaper alternative to human immunoglobulin. We aim to analyze the response and safety profile of anti-D in patients with severe ITP. A retrospective study was conducted at a tertiary care hospital in Northern India. Patients received a single intravenous infusion of 75 µg/kg anti-D. In total, 36 patients (20 females) were included in this study. The median duration from ITP diagnosis to anti-D therapy was 235 days (range 1-1613 days). Four (11.1%) patients received anti-D as an upfront treatment. The patients' platelet counts rose significantly by the end of day three and continued to be significantly high until day 30 of receiving anti-D (p ≤ 0.001). The overall response rate (ORR) by day seven was 88.89%. There was no effect of age, sex, duration of disease, prior therapy, and platelet count on the ORR. Patients were followed up for a median duration of 52 days (longest follow-up: 3080 days). Six (6/36, 16.67%) patients continued to be in remission till the last follow-up. The hemoglobin fall was statistically significant on day three and day seven (p < 0.001 and p = 0.001) and got normalized by day 30. We observed equally good ORR in mixed populations and different phases of ITP along with long-term sustained response. The study demonstrates a quick and high response rate along with good safety profile to anti-D in all forms of ITP.

Weak D type 42: Antigen density and risk of alloimmunization in the province of Québec.

BACKGROUND AND OBJECTIVES: A high proportion of suspected weak D patients referred to Héma-Québec were genotyped as weak D type 42 (368/2105, 17.5%). These patients are currently considered D with regard to RhD immunoprophylaxis in pregnancy and transfusion. The goal of this study was to retrospectively evaluate the risk of alloimmunization in weak D type 42 patients and to characterize their RhD surface molecule expression on red blood cells (RBCs) in comparison to other weak D types (1, 2 and 3). MATERIALS AND METHODS: A retrospective analysis using the weak D type 42 patients' medical data to verify potential anti-D alloimmunization events was conducted. Quantitative analyses using flow cytometry were also performed on RBCs to quantify the cell surface density of the D antigen. RESULTS: Data on 215 subjects with weak D type 42 were reviewed. None developed immune allo-anti-D; three had definite exposure to D+ red cells and 41 had possible exposure through pregnancy. Flow cytometry analysis showed that weak D types 1, 2, 3 and 42 had relative antigen densities of 2.7%, 2.2%, 8.1% and 3.6%, respectively, with R1R2 red cells referencing 100% density. The estimated antigen density range of weak D type 42 was 819-1104 sites per RBC. CONCLUSION: Our retrospective alloimmunization data analysis and antigen density study establish a basis for the consideration of a weak D type 42 individual as D+. This consideration would allow for a targeted reduction of RhD immunoprophylaxis in pregnancy and the unjustified use of D- units for transfusion.

Incidence of anti-D alloimmunization in D-negative individuals receiving D-positive red blood cell transfusion: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: The transfusion of D-negative red blood cells (RBCs) to D-negative patients has been widely adopted to prevent anti-D alloimmunization, especially in women of childbearing age. Still, transfusion of D-positive RBCs to D-negative recipients is occasionally inevitable in practice, and the resulting incidence of anti-D in different D-negative groups of patients has not been well summarized. MATERIALS AND METHODS: We searched the relevant literature using PubMed, Cochrane Library, and Embase databases from inception date to 30 September 2021. We looked for studies of anti-D occurring in D-negative recipients who received D-positive RBC transfusions. The anti-D incidence was summarized with 95% confidence intervals (CIs). Data with similar characteristics were combined using a random-effects model. RESULTS: About 42 studies (2226 cases), which found anti-D, the exact volume of D-positive RBC transfused, and the follow-up time for anti-D detection, met the inclusion criteria. The pooled anti-D incidence was 64% (95% CI, range 55%-74%) in volunteers receiving small volumes of D-positive RBCs, 84% (95% CI, 74%-94%) in those receiving whole units, 26% (95% CI, 19%-32%) in mixed patients, 12% (95% CI, 8%-16%) in oncology patients, 27% (95% CI, 13%-40%) in trauma patients, 4% (95% CI, 0%-8%) in immune-compromised transplant patients, and 6% (95% CI, 1%-39%) in those with AIDS. CONCLUSION: Compared with the high frequency of anti-D in healthy D-negative volunteers given D-positive RBCs, we found a lower rate of anti-D immunization in various D-negative patients and almost none in transplant and AIDS patients.

Following targeted routine antenatal anti-D prophylaxis, almost half of the pregnant women had undetectable anti-D prophylaxis at delivery.

INTRODUCTION: In September 2016, a nationwide targeted routine antenatal anti-D prophylaxis program was implemented in Norway. The prophylaxis (anti-D immunoglobulin) aims to cover the whole third trimester and is administered in gestational week 28 to RhD-negative women who carry RhD-positive fetuses. However, in many women, antibody screening at delivery does not detect anti-D immunoglobulin. The goal of this study was to investigate the presumable role of dose and timing of antenatal anti-D immunoglobulin administration in non-detectable prophylaxis at the time of delivery. MATERIAL AND METHODS: In this retrospective observational study, RhD-negative pregnant women who gave birth at Oslo University Hospital and Akershus University Hospital between January 2017 and December 2019 were analyzed. Women who received antenatal anti-D immunoglobulin (1500 IU at Oslo University Hospital and 1250 IU at Akershus University Hospital) when fetal RHD genotyping at gestational week 24 predicted an RhD-positive fetus were included if an antibody screen at delivery was available. Data from the blood bank, maternity information systems, and electronic patient records were used. RESULTS: Analysis of the 984 RhD-negative women at the two hospitals revealed that 45.4% had non-detectable anti-D at delivery. A significant difference between the two hospitals was observed: 40.5% at Oslo University Hospital (n = 509) and 50.7% at Akershus University Hospital (n = 475) (p = 0.001). The proportion with non-detectable anti-D increased to 56.0 and 75.3%, respectively (p = 0.008) in the group of women who gave birth 12 weeks after routine antenatal anti-D prophylaxis. Significantly fewer women had detectable anti-D at delivery when the lower anti-D immunoglobulin dose (1250 IU) was administered antenatally. Multiple logistic regression indicated that the time interval between routine antenatal anti-D prophylaxis and delivery, in addition to anti-D dose, were significantly associated with detectable anti-D at delivery (p < 0.001). CONCLUSIONS: We do not know which RhD-negative pregnant women, despite antenatal anti-D prophylaxis, are at risk of RhD alloimmunization, when antibody screening is negative at delivery. Administration of antenatal prophylaxis should probably be moved closer to delivery, since the risk of fetomaternal hemorrhage is higher during the last weeks of the third trimester.

Investigating anti-D in an individual with the weak D type 2 genotype.

Anti-D in individuals with a weak D phenotype is an unexpected finding that may require additional investigation to determine whether the anti-D is an autoantibody or alloantibody. Further investigation may also include assessment of the patient's RHD genotype and exclusion of anti-G. We present a case of an 84-year-old man with the weak D type 2 genotype who developed an unexpected anti-D along with anti-C. Individuals with the weak D type 2 genotype are thought not to be at risk for developing alloanti-D, although the distinction between alloanti-D and autoanti-D may be difficult to ascertain. Furthermore, investigations may affect transfusion recommendations. This patient was restricted to crossmatch-compatible, D-C- red blood cells even though the clinical significance of the anti-D was uncertain. This report is one of a few reported cases of an individual with the weak D type 2 genotype with demonstrable anti-D but without evidence for alloanti-D.

Medical therapy to attenuate fetal anaemia in severe maternal red cell alloimmunisation.

Haemolytic disease of the fetus and newborn (HDFN) remains an important cause of fetal mortality with potential neonatal and longer-term morbidity. HDFN is caused by maternal red cell alloimmunisation, with IgG antibodies crossing the placenta to destroy fetal erythroid cells expressing the involved antigen. Intrauterine fetal blood transfusion is the therapy of choice for severe fetal anaemia. Despite a strong evidence base and technical advances, invasive fetal therapy carries risk of miscarriage and preterm birth. Procedure-related risks are increased when invasive, in utero transfusion is instituted prior to 22 weeks to treat severe early-onset fetal anaemia. This review focuses upon this cohort of HDFN and discusses intravenous immunoglobin (IVIg) and novel monoclonal antibody (M281, nipocalimab) treatments which, if started at the end of the first trimester, may attenuate the transplacental passage and fetal effects of IgG antibodies. Such therapy has the ability to improve fetal survival in this severe presentation of HDFN when early in utero transfusion may be required and may have wider implications for the perinatal management in general.