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The actual risk of providing RhD-positive units to RhD-negative recipients remains debatable. There is no standard of care in the United States (US) to guide transfusion decisions regarding RhD type for patients with an unknown blood type, except for women of childbearing age and neonates. The risk of alloantibody formation by an RhD-negative patient exposed to RhD-positive blood is reported to be from 3% to 70%. Due to such wide variations, this review was undertaken to determine the prevalence of anti-D alloimmunization in trauma patients who are RhD-negative and were transfused RhD-positive blood products. This study used the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) approach to answer the question, "In trauma patients who were transfused blood, what is the prevalence of alloimmunization to the D-antigen?" The review included all published articles through April 3, 2022 in databases. Articles published after the search period found by the authors were added to the manuscript if they addressed the primary question and there was unanimous consensus. There were 1683 full-text articles that met the search criteria, with 19 studies meeting eligibility criteria. In addition, 57 references were added after the search period had closed. The incidence of anti-D alloimmunization in adult trauma patients receiving whole blood varied from 7.8% to 42.7%. In contrast, incidence varied in patients receiving red blood cells (RBCs), from 0 to 94%, depending on number of categories analyzed. Anti-D alloimmunization with platelet transfusions varied from 0% to 19%. The alloimmunization rate increased with age and was detected only in children older than 5 years. Recent guidelines recommend the administration of Rh immune globulin (RhIG) to all traumatically injured patients who are both RhD-negative and pregnant. However, there is no specific guidance focused on the RhD-negative patient, pregnant or nonpregnant, and who have received RhD-positive red blood cells (RBC) and platelets. While numerous studies have attempted to evaluate the frequency of RhD alloimmunization rate in trauma settings, emerging data suggests that many factors affect this phenomenon. Additionally, the role of RhIG administration in cases of RhD-incompatible transfusions within the trauma setting adds complexity. As our trajectory propels us towards precision medicine and tailored transfusion practices, gaining a big data approach becomes indispensable.

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The level of anti-D antibodies in human immunoglobulin products for intravenous administration (IVIG) is controlled by the direct haemagglutination method prescribed by the European Pharmacopoeia (Ph. Eur.) that requires 2 control reference reagents. The World Health Organization (WHO) positive control International Reference Reagent (IRR; 02/228) with a nominal titre of 8 defines the highest acceptable titre, while the negative control preparation (02/226) has a nominal titre of <2. Working reference preparations (04/132 and 04/140) were subsequently established as Biological Reference Preparations (BRPs) for the Ph. Eur., and for distribution by the United States Food and Drug Administration (US FDA) and the National Institute for Biological Standards and Control (NIBSC). Due to diminishing stocks of these working reference preparations across the 3 institutions, a joint international study was organised to establish harmonised replacement batches. Sixteen laboratories contributed data to the study to evaluate positive and negative candidate replacement batches (13/148 and 12/300, respectively) against the WHO positive and negative control IRRs and the current working reference preparations (BRPs). The results show that the candidate reference preparations (13/148 and 12/300) are indistinguishable from the corresponding IRRs and current BRPs. The candidate preparations 13/148 and 12/300 were adopted by the Ph. Eur. Commission as Immunoglobulin (anti-D antibodies test) BRP batch 2 and Immunoglobulin (anti-D antibodies test negative control) BRP batch 2 with nominal haemagglutination titres of 8 and <2, respectively. The same materials were also adopted as NIBSC and US FDA reference preparations, thus ensuring full harmonisation.

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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.

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The Black mamba, D. polylepis, is one of the many venomous snakes found in Kenya, and known to account for some snakebite incidents. The Kenyan Ministry of Health data reveals annual 15,000 snakebites occurrences. Also, 1 in 15 people in Kenya gets bitten by a snake, and tragically, 1 in 147 of these individuals die of snakebite yearly. Traditionally, antivenoms for treatment are produced from horse or sheep but have complicated and expensive production issues. Alternative production approaches, such as using IgY antibodies derived from chicken egg yolks, may overcome disadvantages with traditional antivenom manufacturing techniques. In this current study, D. polylepis specific IgY polyclonal antibodies were purified from the egg yolks of chickens immunized with D. polylepis venom. These antibodies were subsequently assessed for their in-vivo neutralizing capacity vis-à-vis commercial antivenoms, PANAF-Premium and VINS. The IgY antibodies were purified by ammonium sulfate precipitation and affinity-chromatography, with quality and specificity determined by SDS-PAGE and ELISA. The LD50 of D. polylepis was found to be 0.54 mg/kg in chicks, and 0.34 mg/kg in mice, respectively. Pool of extracted IgY yielded 2.8 mg/mL concentration. Purified IgY under non-reducing and reducing conditions on SDS-PAGE exhibited a single-protein band of about 183 kDa and two bands (67 kDa and 25 kDa), respectively. The minimum-edematogenic dose was 0.05 µg. Anti-D. polylepis IgY antibodies and two antivenoms demonstrated the capacity to neutralize the toxic activities of D. polylepis venom. This study confirms a successful IgY generation against Black mamba venom for the first time, and observed toxic effects of the venom as well as neutralizing capacity of antivenoms.

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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.

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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.

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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.

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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.

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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.

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Patients with myelodysplastic syndrome (MDS) often need platelet transfusions to address thrombocytopenia. The risk of alloimmunization, particularly in Rhesus (Rh) incompatibility between donors and recipients during platelet transfusions, is heightened, especially with whole blood-derived pooled platelets as opposed to apheresis platelets. Although the occurrence of alloimmunization from platelet transfusions is minimal, there is an ongoing debate about whether Rh immune globulin (RhIg) should be administered to Rhesus D (RhD)-negative recipients of RhD-positive platelet units. We present a unique case of anti-D alloimmunization in a 56-year-old patient with underlying MDS following multiple platelet transfusions but never received packed cell transfusion or anti-D immunoglobulin. Some studies advocate for RhIg administration in specific scenarios and for certain patient populations. This case underscores the importance of considering Rhesus compatibility or administering anti-D immunoglobulin in cases where frequent platelet transfusions are required.

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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.

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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.

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Background: Autoimmune encephalitis is a neurological condition caused by abnormal immune responses, manifesting as cognitive impairments, behavioral abnormalities, and seizures. Its diagnosis depends on the detecting neuronal surface antibodies in serum or cerebrospinal fluid. Despite recent advances in understanding, clinical recognition remains challenging, especially with rare antibodies such as anti-dopamine D2 receptor (D2R) and anti-dipeptidyl-peptidase-like protein 6 (DPPX) antibodies. Delayed diagnosis can lead to severe complications. This case presentation emphasizes the diagnostic intricacies and effective treatment of the anti-D2R and DPPX antibody-associated autoimmune encephalitis. Case description: The patient presented with a 3-day history of fatigue and limb soreness followed by a 3-h episode of confusion and limb convulsions. Upon admission to our facility, the initial diagnosis included status epilepticus, aspiration pneumonia, metabolic acidosis, respiratory alkalosis, and suspected encephalitis. Despite receiving antiepileptic, anti-infection, and antivirus therapy, the patient's condition deteriorated. Both computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain showed no significant abnormalities. No pathogen was identified in the cerebrospinal fluid (CSF). However, further CSF and serum examination revealed positive results of anti-D2R and anti-DPPX antibodies, confirming a diagnosis of anti-D2R and DPPX antibody-associated autoimmune encephalitis. The patient underwent a comprehensive treatment regimen, including high-dose methylprednisolone pulse therapy combined with intravenous immunoglobulin (IVIG), antiviral and anti-infection treatments, and antiepileptic medications. Significant clinical improvement was observed, and by the 18th day of admission, the patient was stable and coherent. Conclusions: The current patient represents the first reported case of double-positive autoimmune encephalitis for anti-D2R and DPPX antibodies, with epilepsy as a prominent feature. High-dose methylprednisolone pulse therapy combined with IVIG has shown significant safety and efficacy in treating anti-D2R and DPPX antibody-positive autoimmune encephalitis-associated epilepsy.

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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.

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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.

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OBJECTIVES: Identification of DNT, a rare partial D, can be challenging, as it is difficult to distinguish from D+. This study aimed to identify DNT individuals by analyzing the DNT proband's family members, characterize DNT, and propose management strategies. METHODS: Family members of the first Korean DNT proband were recruited. RHD genotyping was conducted, and weak D tests were carried out using several anti-D reagents. RESULTS: Three DNT individuals were identified among 6 family members, including 1 with an anti-D alloantibody. As DNT red cells exhibited strong reactivity with all anti-D clones, DNT was serologically indistinguishable from D+. Moreover, unusual serologic findings in DNT individuals only became apparent after anti-D alloimmunization. CONCLUSIONS: We recommend DNT individuals as candidates for Rh immune globulin prophylaxis during the perinatal period and transfusions with D- blood components. An anticipatory RHD genotyping is suggested for partial D family members to prevent potential partial D individuals from becoming alloimmunized.

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This article summarizes the current situation of anti-D immunoglobulin (anti-D-Ig) use in RhD-negative pregnant women at home and abroad. The article describes the concept, research and development history, and domestic and foreign applications of anti-D-Ig and points out that anti-D-Ig has not been widely used in China, mainly due to reasons such as unavailability in the domestic market and non-standard current application strategies. The article focuses on analyzing the genetic and immunological characteristics of RhD-negative populations in China. The main manifestations were that the total number of hemolytic disease of the newborn (HDN) relatively high and D variant type. In particular, there are more Asian-type DEL, the importance of clinical application of anti-D-Ig was pointed out, and its antibody-mediated immunosuppressive mechanism was analyzed, which mainly includes red blood cell clearance, epitope blocking/steric hindrance, and Fc γ R Ⅱ B receptor mediated B cell inhibition, anti-D-Ig glycosylation, etc.; clarify the testing strategies of RhD blood group that should be adopted in response to the negative initial screening of pregnant and postpartum women; this article elaborates on the necessity of using anti-D-Ig in RhD-negative mothers after miscarriage or miscarriage, as well as the limitations of its application both domestically and internationally. It also proposes a solution strategy for detecting RhD blood group incompatibility HDFN as early as possible, diagnosing it in a timely manner, and using anti-D-Ig for its prevention and treatment. If the DEL gene is defined as an Asian-type DEL, anti-D-Ig prophylaxis in women would be unnecessary. Finally, based on the specificity of RhD-negative individuals, the article looks forward to the application trend of anti-D-Ig in China. It also called for related drugs to be listed in China as soon as possible and included in medical insurance.

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Anti-D alloimmunization in the first trimester of pregnancy has long been the subject of prevention with anti-D immunoglobulins during events at risk of fetomaternal hemorrhage. Although the efficacy of preventing anti-D alloimmunization by an injection of immunoglobulin at 28 weeks of gestation (WG) is obvious, the literature provides little evidence of the effectiveness before 12+6 WG and several countries have modified their recommendations. In the presumed absence of a difference in alloimmunization risk between early and late prevention, our objective was to evaluate and compare the cost of treatment for 3 alloimmunization prevention strategies in France, the United Kingdom, and the Netherlands. This was a single-center retrospective study. Our target population included all women who received anti-D immunoglobulins (Rhophylac) in the first trimester of pregnancy before 12+6 WG at Nantes University Hospital in 2018 (N = 356). Within the target population, 2 other populations were constituted based on British (N = 145) and Dutch (N = 142) clinical practice guidelines (CPG). These 3 populations were analyzed for the comparative cost of treatment for prevention from a health system perspective. The average cost of Rhophylac alloimmunization prevention for 1 episode was €117.8 from a health system perspective. The total cost attributed to prevention in 2018 at Nantes University Hospital (N = 356) was €41,931.4 according to this perspective. If the UK CPG or Dutch CPG had been applied to the Nantes target population, a saving of around 60% would have been achieved. At the national level, the cost according to the health system perspective specifically attributable to induced abortion (N estimated = 26,916) could represent a total cost of €3,170,704. This study highlighted the high cost of the French prevention strategy in the first trimester of pregnancy compared with British or Dutch strategies. The modification of our practices would allow substantial financial savings to the French health system but would also avoid the nonrecommended exposure to a blood product at this term, would allow a faster medical management and a relief of the care system.

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BACKGROUND: Transplacental-derived anti-D IgG in RhD-negative pregnant women can trigger an immune response to Rh D-positive red cells in fetuses and newborns. We assessed the effect of anti-D titers in RhD-negative pregnant women on fetuses and newborns. METHODS: The clinical data of 142 singleton RhD-sensitized pregnancies were retrospectively collected. The pregnant women received routine prenatal care and the newborns had standard care. Based on the tertile categories of the pregnancies, the maximum titers of anti-D IgG in the pregnant women were divided into three groups ranging from low to high as follows: low-titer group (anti-D titer: 1:4-1:128, n = 57); medium-titer group (anti-D titer: 1:256-1:512, n = 50); and high-titer group (anti-D titer: 1:1024-1:4096, n = 35). RESULTS: The frequencies of major neonatal complications did not significantly differ among the three groups. The high-titer group had the highest frequency of pregnancies requiring intrauterine transfusion (IUT) and number of IUTs among the three groups. The high-titer group had a significantly higher frequency of newborns treated with top-up transfusion, number of top-up transfusions, frequency of newborns treated with exchange transfusion (ET), and number of ETs when compared to the low-titer group. CONCLUSION: Higher anti-D titers in RhD-negative pregnant women predict more severe fetal and neonatal hemolytic anemia. Increasing maternal anti-D titers results in an increased need for IUTs, and neonatal top-up transfusions and ETs. Methods for reducing titers of anti-D IgG in RhD-sensitized pregnant women warrants further investigation.

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The D antigen of the Rh blood group is considered clinically significant due to its ability to cause hemolytic transfusion reactions and hemolytic disease in the fetus and newborn. This systematic review discusses the prevalence of RhD variants among pregnant women and the importance of including RhD genotyping for prenatal testing to detect RhD variants and prevent anti-D alloimmunization. A comprehensive literature search was conducted using scientific search engines, including PubMed and MEDLINE databases, with the keywords 'anti-D alloimmunization', 'RhD variant', and 'pregnant women.' The review adhered to the PRISMA guidelines. Meta-analysis was performed using MedCalc version 20. A significance level of p≤0.05 was considered statistically significant for all two-tailed tests. The meta-analysis included four articles that met the inclusion criteria. The total prevalence of RhD positivity (RhD+) was 61% (95% CI:34%-85%). The prevalence ranged from 22% to 82%, indicating a high degree of heterogeneity between studies (I2=98.71%, p<0.0001). The overall prevalence of D variants was 15% (95% CI, 9%-23%) with a prevalence of 0.05% to 100%, showing a high degree of heterogeneity between studies (I2=99.89%, p<0.0001). Anti-D alloimmunization could occur in pregnant women with some types of RhD variants. All four studies focused on molecular testing of samples showing inconsistent or weak results with at least two anti-D antibodies using serological methods.

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