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BACKGROUND: The current study was initiated to evaluate the comparability of fetomaternal hemorrhage (FMH) measurement using flow cytometry (FCM) and Kleihauer–Betke test (KBT) and also to evaluate the validity of the current anti-D immunoglobulin doses for the prevention of hemolytic disease of the newborn in Duhok/Iraq. MATERIALS AND METHODS: The current study included 101 pregnant women with Rh(D)-negative blood group who had Rh (D)-positive husbands. Their blood was tested for blood groping, FMH by FCM and KBT, and indirect Coombs test, 1 h following sensitizing events and 72 h after giving anti-D. Furthermore, blood from newborns was examined for blood group and direct Coombs test. RESULTS: The main sensitizing event was parturition (62.4%) followed by cesarean section (32.7%). The indirect Coombs was positive in 32 cases while the direct Coombs test was positive in 19 cases. In 63.4% of cases, the ABO blood groups were incompatible between mothers and their babies. When FMH was checked by KBT method, it was found that 16 (15.8%) participants had FMH ranging 1.2–51 mL (median 4.35 mL), while FMH was positive in 27 (26.7%) participants by FCM method ranging 1.2–54.4 ml (median 9.5 mL). About 4–5 patients had FMH (measured by KBT and FCM, respectively) of >12 mL and only 1% had a volume of >30 mL. The difference between KBT and FCM for FMH measurement was statistically significant with P < 0.001 when assessed by paired t-test and has a highly significant positive correlation with each other. The correlation of FMH was statistically significant with maternal gravidity, number of anti-D received before (moderate positive correlation), gestational age, and newborn hemoglobin (negative correlation). However, the correlation was not significant between FMH and the following factors: maternal parity, maternal hematological parameters, and ABO compatibility of mother and their babies with P > 0.05. CONCLUSION: Inadequate doses of anti-D had been given previously that resulted in sensitization in at least one-quarter of the cases, and this necessitated proper measurement of FMH in all Rh (D) mothers following sensitizing events.

• This article introduces the concept, research history, and applications of anti-D-Ig. • The reasons why anti-D-Ig has not been widely used in China was pointed out. • The importance of clinical application of anti-D-Ig was analyzed. • The necessity and limitations of using anti-D-Ig were elaborated. • The application trend of anti-D-Ig in China was anticipated. 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. [ABSTRACT FROM AUTHOR]

Thomas Larsen Titze,1 Lars Henrik Dahl Hamnvik,2 Inga Marie Hauglum,1 Anne Elisabeth Tonay Carlsen,2 Lena Tjeldhorn,3 Nhan Trung Nguyen,3 Çiğdem Akalın Akkök3 1Department of Laboratory Medicine, Vestre Viken Health Trust, Drammen, Norway; 2Department of Hematology, Vestre Viken Health Trust, Drammen, Norway; 3Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, NorwayCorrespondence: Çiğdem Akalın Akkök, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Ullevaal, Kirkeveien 166, Oslo, N-0407, Norway, Tel +47 92 03 47 47, Fax + 47 22 11 88 50, Email cigdemakak@yahoo.noAbstract: Blood transfusion is life-saving in massive hemorrhage. Before pre-transfusion tests with ABO and RhD typing results are available, O RhD negative packed red blood cell (PRBC) units are used without cross-matching in emergency. RhD negative girls and women of child-bearing age should always receive RhD negative blood transfusions to prevent RhD-alloimmunization because anti-D-related hemolytic disease of fetus and newborn (HDFN) can result in mild to severe anemia, and in a worst-case scenario death of an RhD positive fetus and/or newborn. However, “wrong blood to wrong patient” happens unintentionally. Here we report an emergency blood transfusion with one unit of RhD positive PRBCs to an RhD negative young woman when estimated blood loss was 2500 mL during delivery and surgical removal of retained placenta. Realizing the mistake, management with high dose anti-D immunoglobulin (Ig) was initiated to remove the RhD positive red blood cells (RBCs) from the patient’s circulation. Such mitigation is recommended only for girls and women of child-bearing age. Follow-up was performed by flow cytometry until RhD positive RBCs were no longer detected. Ten months after the delivery, antibody screening was negative. However, we still do not know whether we managed to prevent RhD-alloimmunization.Keywords: anti-D antibody, anti-D immunoglobulin, alloimmunization, fetomaternal hemorrhage, pregnancy, Rhesus

The use of Rho(D) immune globulin in Rh-negative pregnant women has become standard of care, but many practicing clinicians do not know the dosing recommendations for this essential medication. In this article, we describe a case of a 15-year-old girl who presented with intrauterine fetal demise and was found to have massive fetomaternal hemorrhage. Kleihauer-Betke testing results indicated nearly 460 mL of fetal blood in the maternal circulation. The patient ultimately received 4800 µg of Rho(D) immune globulin, a dose that required close coordination with the obstetrical service and pharmacy. Although this is an unusual case of large-volume, potentially chronic, fetomaternal hemorrhage, it is also an excellent illustration of the principles for diagnosing this condition, as well as providing dosing guidelines for Rho(D) immunoglobulin to prevent alloimmunization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Maternal-fetal Rh-alloimmunization is a rare but potentially fatal event, most often caused by maternal exposure to D-antigen-presenting Rh-positive erythrocytes at the time of delivery. Prophylaxis with anti-D immune globulin is highly effective with a low side-effect profile and results in a dramatically decreased risk of alloimmunization. Postpartum anti-D immune globulin prophylaxis is recommended by national societies to reduce Rh-alloimmunization. We hypothesized that a small number of postpartum patients do not receive prophylaxis as indicated. OBJECTIVE: We investigated patients in 2 separate health systems that did not receive indicated prophylaxis and devised a suite of Electronic Health Record interventions to prevent future errors. STUDY DESIGN: We reviewed charts retrospectively from Electronic Health Record data of 2 urban academic health systems, the MetroHealth System and Oregon Health & Science University. We identified all Rh-negative postpartum patients and their infants delivering from 2014 to 2019. The primary outcome was the proportion of postpartum patients not receiving indicated anti-D immune globulin prophylaxis. Once cases of missed anti-D immune globulin prophylaxis were identified, we reviewed individual charts to determine the relevant clinical circumstances and potential causes for error. RESULTS: Of 29,801 deliveries over 5 years (15,444 at MetroHealth System and 14,357 at Oregon Health & Science University), there were 3087 Rh-negative postpartum patients, of whom 7 were alloimmunized and ineligible for prophylaxis. Anti-D immune globulin was indicated for 2162 (70.0%) women as they delivered an Rh-positive infant. A total of 37 indicated patients did not receive postpartum anti-D immune globulin. Twenty patients were offered prophylaxis and declined. We missed a total of 17 opportunities, thus our institutions appropriately offered indicated anti-D prophylaxis to 99.2% of patients over a period of 5 years. Of the 17 true misses, anti-D immune globulin was ordered for some patients, whereas others did not have an anti-D immune globulin order placed. A toolkit in the Electronic Health Record consisting of decision-support hard stops, automated documentation, and longitudinal reporting was implemented at the MetroHealth System in the year after its inception. The Toolkit identified and helped prevent 4 potential misses, resulting in a 100% anti-D prophylaxis rate at the MetroHealth System. CONCLUSION: Given the serious nature of Rh-alloimmunization, we believe missed prophylaxis should be a never event. Through examination of our current processes, we identified areas of improvement and developed a Postpartum Anti-D Immune Globulin Prophylaxis Electronic Health Record Toolkit, which showed improvement in administration rates. Such a toolkit has the potential to identify patients appropriately and avoid missed anti-D immune globulin prophylaxis events.

Objective: The objective of this study was to audit the use of anti-D immunoglobulin (anti-D) against the current Australian guidelines in one large inner-city referral hospital over three years and critique the practice identified. Background: Pregnant patients who have a D-negative (RhD negative) blood type are at risk of D alloimmunisation if a potentially sensitising event occurs during pregnancy or birth. The administration of anti-D Ig can prevent complications related to alloimmunisation. Potentially sensitising events commonly present to the emergency department requiring the administration of anti-D Ig in line with current guidelines. Study Design and Methods: This is a retrospective cohort study of all patients who received anti-D Ig in a large inner-city emergency department (ED) over three years (July 2014 - June 2017). Indications for administration were scrutinised against current guidelines by experienced clinicians. Results: A total of 228 patients received anti-D Ig, with the majority being less than twelve weeks in gestation (169, 74.1%). Anti-D Ig was administered without support from the guidelines in 81 (35.5%) patients, with a lack of documented sensitising event in 77 (95%) of these cases. Discussion and Conclusion: There were inconsistencies amongst clinicians who prescribe anti-D Ig in the ED, and a lack of the application of current guidelines. This may stem from a lack of empirical evidence about the need for anti-D Ig in the most common group presenting to EDs, those under twelve weeks in gestation. Current guidelines also fail to take into consideration future need, which could be incorporated in future, ED specific anti-D Ig guidelines. Implications for research, policy, and practice: This audit identified overuse of anti-D Ig in the ED. This may stem from the absence of evidence for its use in pregnant patients under 12 weeks in gestation. To reduce unsupported use, further data on alloimmunisation rates following potentially sensitising events in early pregnancy would be helpful. Additional guidelines specific to patients under 12 weeks in gestation, and presenting to the emergency department may reduce some unsupported usage. What is already known about the topic? * Pregnant patients who have an D-negative blood type are at risk of D alloimmunisation when a sensitising event occurs. *It is common for patients to present to the emergency department with complications in early pregnancy * Previous work has shown that there is variation in anti-D Ig administration in the emergency department. What this paper adds: * There is significant use of anti-D Ig in the emergency department that is outside of current guidelines. * The current guidelines may not serve the needs of the majority of presentations in the emergency department. *Further data on alloimmunisation rates following potentially sensitising events in patients less then twelve weeks of gestation would be useful. [ABSTRACT FROM AUTHOR]

Abstract Background High-throughput non-invasive prenatal testing (NIPT) for fetal Rhesus D (RhD) status could avoid unnecessary treatment with anti-D immunoglobulin for RhD-negative women found to be carrying an RhD-negative fetus. We aimed to assess the diagnostic accuracy of high-throughput NIPT for fetal RhD status in RhD-negative women not known to be sensitized to the RhD antigen, by performing a systematic review and meta-analysis. Methods Prospective cohort studies of high-throughput NIPT used to determine fetal RhD status were included. The eligible population were pregnant women who were RhD negative and not known to be sensitized to RhD antigen. The index test was high-throughput, NIPT cell-free fetal DNA tests of maternal plasma used to determine fetal RhD status. The reference standard considered was serologic cord blood testing at birth. Databases including MEDLINE, EMBASE, and Science Citation Index were searched up to February 2016. Two reviewers independently screened titles and abstracts and assessed full texts identified as potentially relevant. Risk of bias was assessed using QUADAS-2. The bivariate and hierarchical summary receiver-operating characteristic (HSROC) models were fitted to calculate summary estimates of sensitivity, specificity, false positive and false negative rates, and the associated 95% confidence intervals (CIs). Results A total of 3921 references records were identified through electronic searches. Eight studies were included in the systematic review. Six studies were judged to be at low risk of bias. The HSROC models demonstrated high diagnostic performance of high-throughput NIPT testing for women tested at or after 11 weeks gestation. In the primary analysis for diagnostic accuracy, women with an inconclusive test result were treated as having tested positive. The false negative rate (incorrectly classed as RhD negative) was 0.34% (95% CI 0.15 to 0.76) and the false positive rate (incorrectly classed as RhD positive) was 3.86% (95% CI 2.54 to 5.82). There was limited evidence for non-white women and multiple pregnancies. Conclusions High-throughput NIPT is sufficiently accurate to detect fetal RhD status in RhD-negative women and would considerably reduce unnecessary treatment with routine anti-D immunoglobulin. The applicability of these findings to non-white women and women with multiple pregnancies is uncertain.

Background: Rh(D) alloimmunization prophylaxis should be administered to unsensitized Rh(D)-negative pregnant women. A routine antenatal dose and a postpartum dose for women that delivered an Rh(D)-positive neonate are recommended. Due to a very low prevalence of Rh(D)-negative blood type in Thai population, awareness of this specific management may be lacking. Objective: To determine the proportion of unsensitized Rh(D)-negative pregnant women that delivered at Siriraj Hospital who received a complete course of anti-D immunoglobulin and to determine the factors associated with the failure to achieve a complete administration as well as pregnancy and neonatal outcomes. Materials and Methods: Medical records of 133 unsensitized Rh(D)-negative pregnant women were reviewed to determine the proportion of cases receiving a complete anti-D prophylaxis. Possible reasons for missing anti-D administration were postulated. Comparison between cases receiving and not receiving antenatal anti-D prophylaxis was performed in terms of associated factors. Pregnancy and neonatal outcomes were compared between women who received complete prophylaxis and those who did not. Results: A complete anti-D prophylaxis was obtained in 71.4% of the women with antenatal dose given to 78.2%. Late antenatal care (OR 2.6, 95% CI 1.4 to 4.9) and late or no antenatal care at Siriraj Hospital (OR 7.1, 95% CI 2.8 to 17.9) were associated with missing antenatal anti-D administration. Desire for tubal sterilization and positive maternal Rh(D)-antibody in the third trimester appeared to be the causes of postpartum dose omission. Pregnancy and neonatal outcomes were comparable between women receiving and not receiving a complete anti-D prophylaxis. Conclusion: The proportion of unsensitized Rh(D)-negative pregnant women delivering at Siriraj Hospital who received a complete anti-D prophylaxis was 71.4%. Late antenatal care, late or no antenatal care at Siriraj Hospital, desire for tubal sterilization, and positive maternal Rh(D)-antibody in the third trimester were associated with the incomplete Rh(D) alloimmunization prophylaxis. [ABSTRACT FROM AUTHOR]

The introduction of anti‐Rh(D) immunoglobulin more than 50 years ago has resulted in only a 50% decrease in Rhesus disease globally owing to a low uptake of this prophylactic approach. The International Federation of Gynecology and Obstetrics, International Confederation of Midwives, and Worldwide Initiative for Rhesus Disease Eradication have reviewed current evidence regarding the utility of anti‐Rh(D) immunoglobulin. Taking into account the effectiveness anti‐Rh(D), the new guidelines propose adjusting the dose for different indications and prioritizing its administration by indication. These FIGO/ICM guidelines review the evidence regarding the usefulness of anti‐Rh(D) immunoglobulin, prioritizing its administration by indication. [ABSTRACT FROM AUTHOR]

Abstract Background The determination of foetal Rhesus D (RHD) status allows appropriate use of IgRh prophylaxis by restricting its use to cases of RHD feto-maternal incompatibilities. There is a degree of uncertainty about the cost-effectiveness of foetal RHD determination, yet screening programs are being introduced into clinical practice in many countries. This paper evaluates the impact of non-invasive foetal Rhesus D (RHD) status determination on the costs of managing RHD-negative pregnant women and on the appropriate use of anti-D prophylaxis in a large sample of RHD-negative pregnant women using individual prospectively collected clinical and economic data. Methods A prospective two-armed trial of RHD negative pregnant women was performed in 11 French Obstetric Departments. Non-invasive foetal RHD genotyping was performed before 26 weeks' gestation in the experimental arm whereas the control arm participants received usual care. The costs associated with patient management in relation to their RHD negative status (biological tests, anti-D prophylaxis and visits) were calculated from inclusion to the end of the postpartum period. The costs of hospital admissions during pregnancy and delivery were also determined. Results A total of 949 patients were included by 11 centres between 2009 and 2012, and 850 completed follow-up, including medical and biological monitoring. Patients were separated into two groups: the genotyping group (n=515) and the control group (n=335). The cost of the genotyping was estimated at 140 euros per test. The total mean cost per patient was estimated at €3,259 (SD ± 1,120) and €3,004 (SD ± 1,004) in the genotyping and control groups respectively. The cost of delivery represented three quarters of the total cost in both groups. The performance of managing appropriately RHD negative anti-D prophylaxis was 88% in the genotyping group, versus 65% in the control group. Using the costs related to RHD status (biological tests, anti-D immunoglobulin injections and visits) the incremental cost-effectiveness ratio (ICER) was calculated to be €578 for each percentage gain in women receiving appropriate management. Conclusion Early knowledge of the RHD status of the foetus using non-invasive foetal RHD genotyping significantly improved the management of RHD negative pregnancies with a small increase in cost. Trial registration Clinical trials registry-NCT00832962–13 January 2009 - retrospectively registered.

Rhesus-conflict is a pathological condition that manifests itself in the formation of antibodies against fetal erythrocytes in the body of pregnant woman due to the incompatibility of maternal and fetal Rh-factors. The main causes of morbidity and mortality in rhesus conflict are intrauterine hemolytic anemia, fetal hydrops, hemolytic neonatal disease. In addition, an important factor contributing to the increase in perinatal losses in this pathology is the high birth rate of extremely immature children. The reason for this is a preterm labor induction in case of a threat to the life of the fetus, as well as premature births associated with a variety of fetal manipulations. The number of cases of this pathology has declined dramatically throughout the world over the last decades, due to the widespread coverage of women at risk of immunization (anti-D - immunoglobulin). Unfortunately, in Ukraine this situation is not uncommon to this day. The article covers the main modern views on the causes, pathogenesis, course and prevention of immunological conflict associated with incompatibility of the Rh factor in terms of evidence-based medicine. The article describes the experience gained during recent years and attempts to unify the prognostic and preventive approaches in this area. Conclusions: 1. Rhesus-conflict remains a serious problem of domestic medicine with a significant contribution to perinatal loss. 2. Proper and timely anti-Rh immune prophylaxis among all non-immunized women can significantly reduce the incidence of severe disease in fetuses and newborns. 3. There are no remedies for Rhesus conflict. Treatment is subjected to severe hemolytic disease only that occurs before the fetal maturity. Intrauterine hemotransfusion allows prolonging such pregnancy and preventing antenatal fetal death.

• Incidence of anti-D alloimmunization is estimated at 0.9 per 1000 births in France. • Anti-D immunoprophylaxis reduced the incidence of alloimmunization by 80%. • The value of anti-D prophylaxis in the first trimester has never been demonstrated. • In 2018, prevention in the first trimester of pregnancy cost €42,000 in our hospital. • Change of practice in France could reduce costs by around 60%. 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. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1–8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. Materials and methods: A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh − ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Results: Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p =.038,.018, respectively. Significant direct positive dose response correlation (r = 0.78, p =.005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01–8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19–10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Conclusions: Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV infection. A brief rational: Pregnant women with HCV infection are at risk of adverse obstetric outcome. Anti-D Ig therapy may be a risk factor for HCV infection. Hence, we conducted a cross sectional study with the objectives to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. We found that anti-HCV and HCV-RNA seroprevalence were significantly higher in women with anti-D Ig. In addition, women with anti-D Ig therapy were 3.6 times more at risk of positive HCV-RNA with genotype HCV-1b showed higher prevalence. Therefore, anti-D Ig therapy is a risk factor for acquiring HCV infection and we recommend screening for HCV for all recipients of anti-D Ig. In addition, the diagnosis of HCV infection, should be made with HCV antibodies and HCV-RNA detection. [ABSTRACT FROM AUTHOR]

Background and Objectives: The purpose of the study was to evaluate a lyophilized anti‐D immunoglobulin preparation to serve as a replacement WHO International Standard for the calibration of potency assays of anti‐D immunoglobulin products. Such products are used to prevent haemolytic disease of the foetus and newborn due to maternal alloanti‐D. Materials and Methods: The candidate 3rd International Standard for anti‐D immunoglobulin (16/332) was evaluated and calibrated against the 2nd International Standard for anti‐D immunoglobulin (01/572), along with a coded duplicate, a second candidate preparation (16/278) and a comparability sample (16/272) in an international collaborative study. Twenty of 21 laboratories in 15 countries performed one or more of the three European Pharmacopoeia reference methods. Results: The overall geometric mean potency (from all methods) of the candidate 3rd International Standard, 16/332, was 296·6 IU/ampoule, with inter‐laboratory variability, expressed as % GCV, of 4·7%. SE‐HPLC of the immunoglobulin preparations demonstrated combined monomeric and dimeric IgG peak areas of >95% for all samples. Accelerated stability studies have shown both 16/332 and 16/278 to be very stable for long‐term storage at −20°C. Conclusions: Preparation 16/332 was established by the World Health Organisation Expert Committee on Biological Standardization as the 3rd International Standard for anti‐D immunoglobulin with an assigned potency of 297 IU/ampoule. [ABSTRACT FROM AUTHOR]

The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG) when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women.

Introduction: Hepatitis C virus (HCV) infection is a serious health problem. It is a major contributor to end-stage liver disease. Worldwide, 1-8% of all pregnant women were infected. Women with viral hepatitis may be at an increased risk of pregnancy complications. There are several obstetrics intervention acts as risk factors, which are specific to women pertaining the HCV infection; anti-D immunoglobulin (Ig) therapy may be one of them. Our objectives were to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. Materials and methods: A cross sectional study was conducted. A sample of 154 Rhesus negative (Rh - ve) pregnant women regardless of the anti-D Ig therapy was collected. Anti-HCV were tested using third generation enzyme immunoassay (EIA-3) and immunoblot assay (Lia Tek-111), subsequently. In addition, 89 serum samples were subjected to molecular analysis using RT-PCR and DNA enzyme immunoassay (DEIA) method for the detection of HCV-RNA and genotypes. Results: Anti-HCV, and HCV-RNA seroprevalence were significantly higher (17.1, 35.5%) among women with anti-D Ig than their counter group (6.4, 13.16%), p = .038, .018, respectively. Significant direct positive dose response correlation (r = 0.78, p = .005) had been seen between number of anti-D Ig therapy and anti-HCV seropositive rate. Anti-D Ig therapy act as a risk factor (odds ratio (OR) = 3.01, 95%CI: 1.01-8.9) especially from the third dose onward. Women with anti-D Ig therapy were at higher risk (3.6 times more) of positive HCV-RNA (OR =3.6, 95%CI =1.19-10.837). Genotype HCV-1b showed higher prevalent (52.9%) among the recipients of anti-D Ig therapy while genotype HCV-3a (6.6%) was the lowest. Conclusions: Our study showed that Anti-D immunoglobulin therapy acts as a risk factor for acquiring HCV infection. Screening for HCV should be recommended for all recipients of anti-D Ig. Not only HCV antibodies but HCV-RNA detection being recommended for the diagnosis of HCV infection. A brief rational: Pregnant women with HCV infection are at risk of adverse obstetric outcome. Anti-D Ig therapy may be a risk factor for HCV infection. Hence, we conducted a cross sectional study with the objectives to estimate the prevalence of HCV antibodies (anti-HCV), RNA, and genotype distribution among women with anti-D Ig therapy. We found that anti-HCV and HCV-RNA seroprevalence were significantly higher in women with anti-D Ig. In addition, women with anti-D Ig therapy were 3.6 times more at risk of positive HCV-RNA with genotype HCV-1b showed higher prevalence. Therefore, anti-D Ig therapy is a risk factor for acquiring HCV infection and we recommend screening for HCV for all recipients of anti-D Ig. In addition, the diagnosis of HCV infection, should be made with HCV antibodies and HCV-RNA detection. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to compare national guidelines on the prevention of RhD alloimmunization. Study Design We performed a review of four national guidelines on prevention of alloimmunization from the American Congress of Obstetricians and Gynecologists, Royal Collegeof Obstetricians and Gynaecologists, Society of Obstetricians and Gynaecologists of Canada, and The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. We compared the indications/contraindications, timing, dosing, formulation and route of anti-D immune globulin, and management of unique circumstances. The references were compared with regard to the number of randomized control trials, Cochrane Reviews, and systematic reviews/meta-analyses cited. Results Variation exists in recommendations on the timing and need for consent prior to routine antenatal anti-D immune globulin administration, prophylaxis for unique circumstances (e.g., threatened abortion < 12 weeks, complete molar pregnancy), and the use of cell-free fetal DNA testing for fetal RhD genotype. Conclusion These variations in recommendations reflect the heterogeneity of the literature on the prevention of alloimmunization and highlight the need for synthesis of evidence to create an international guideline on prevention of alloimmunization. This may improve safety, quality, optimize outcomes, and stimulate future trials. [ABSTRACT FROM AUTHOR]

Background and aim: Rh isoimmunization still contributes to the neonatal morbidity and mortality due to nonimmunization, under-immunization, and in rare cases, false Rh typing. The main objective of this study was to determine the prevalence of Rh incompatibility, mothers' knowledge about Rh incompatibility, mothers' knowledge about anti-D immunoglobulin and to show the pregnancy outcome of Rh negative mothers. Methods: A cross-sectional study was carried out at the Maternity and Children Hospital in Arar city from November 2016 to May 2017. All pregnant mothers attending the Maternity and Children Hospital for pregnancy follow up or delivery, during the study period were studied. Data were collected by means of personal interview with the sampled population using a researcher-made questionnaire covering the needed data. Data were analyzed by SPSS version 16, using descriptive statistics and Chi-Square test. Results: Of the studied mothers, 23% were Rh negative. Only 38% of the studied mothers had knowledge about Rh incompatibility, 68.5% had knowledge about anti-D and 51% had knowledge about time of administration of anti D. Considering pregnancy outcome; 55% of the delivered babies needed incubation after delivery, 23.3% of those babies were born to Rh negative mothers. However, 6.7% of the incubated children died after incubation (47.8% of them belong to Rh negative mothers). Conclusion: About a quarter of the mothers in the studied population were Rh negative. Mothers had a low level of knowledge about Rh incompatibility and anti-D immunoglobulin and its administration. Health education sittings are needed to increase public awareness about this important issue. [ABSTRACT FROM AUTHOR]

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Management of an Rh(D)-negative alloimmunized pregnant woman has been a major challenge in obstetrics ever since Landsteiner reported the association of this condition with haemolytic disease of the foetus and newborn. In the past five decades through an incremental progress on the clinical side regarding the pathophysiology, intrauterine evaluation of severity of haemolytic process in the foetus initially through amniocentesis and currently by non-invasive methods, the foetus can be treated successfully at a prehydropic stage through intrauterine blood transfusion and later for neonatal haemolytic anaemia in specialized centres. A dramatic fall was recorded in perinatal mortality due to isoimmunization (45/100,000 before 1969 to 1.6/100,000 in 1990 in the UK). Currently in specialized centres, most of these newborns can be saved without any long-term neurological sequelae. At the same time, introduction of anti-D immunoglobulin has played an important role by reducing the incidence of isoimmunized women from 16% to 0.8% if the guidelines for immunization are correctly followed. This review article traces some key milestones, followed by the pathophysiology of the condition and management of Rh-negative non-sensitized and sensitized pregnant women. The non-invasive monitoring technique for Rh(D)-isoimmunized women will be highlighted in detail as this alone has had a major impact in the early diagnosis of the affected foetus that is likely to require invasive monitoring and intrauterine transfusion.

The use of Rho(D) immune globulin in Rh-negative pregnant women has become standard of care, but many practicing clinicians do not know the dosing recommendations for this essential medication. In this article, we describe a case of a 15-year-old girl who presented with intrauterine fetal demise and was found to have massive fetomaternal hemorrhage. Kleihauer-Betke testing results indicated nearly 460 mL of fetal blood in the maternal circulation. The patient ultimately received 4800 µg of Rho(D) immune globulin, a dose that required close coordination with the obstetrical service and pharmacy. Although this is an unusual case of large-volume, potentially chronic, fetomaternal hemorrhage, it is also an excellent illustration of the principles for diagnosing this condition, as well as providing dosing guidelines for Rho(D) immunoglobulin to prevent alloimmunization., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Informed decision-making around anti-D immunoglobulin (Ig) is important but complex, requiring consideration of individual factors to reach the most appropriate choices for individual women. Aims: This research aimed to develop understanding of midwives' practices when offering anti-D Ig to RhD-negative women. Methods: A descriptive, qualitative study was used. Two focus groups were held with 11 midwife participants from two Scottish maternity units. Data were analysed using thematic analysis within a framework approach. Findings: When offering anti-D Ig, midwives were limited in their ability to fully engage with women in a process of individual informed decisionmaking, due partly to their own knowledge and understanding and partly to organisational culture and support. Conclusions: When interventions are recommended and offered routinely, it is challenging to extend the principles of woman-centred individualised care to facilitate meaningful decision-making. More effort is required to understand the difficulties faced by midwives. [ABSTRACT FROM AUTHOR]

OBJETIVO: avaliação da hemorragia feto-materna (HFM) nas pacientes que receberiam profilaxia da aloimunização Rh com emprego de imunoglobulina anti-D (300 mig), pós-aborto precoce. MÉTODO: foram admitidas no estudo pacientes do grupo sanguíneo Rh negativo, com parceiro Rh positivo ou ignorado, com quadro de aborto até 12 semanas de gestação internadas para curetagem uterina. Uma amostra de 5 ml de sangue venoso destas pacientes foi obtida após o procedimento, na qual realizamos o teste qualitativo de roseta para detectar quais casos necessitariam determinação quantitativa do volume de sangue fetal transferido para circulação materna, que foi então apurado pelo teste de Kleihauer-Betke (K-B). RESULTADOS: das 26 pacientes avaliadas, em uma o teste de roseta foi positivo, e o teste de K-B apontou HFM de 1,5 ml. CONCLUSÕES: a dose de imunoglobulina anti-D nos casos de abortamento até a 12ª semana de gestação deveria ser substancialmente reduzida, parecendo-nos oportuna a disponibilização no mercado nacional de apresentação com 50 mig, que representaria além da economia, maior racionalidade.OBJECTIVE: evaluation of fetomaternal hemorrhage (FMH) in patients who would need Rh alloimmunization with anti-D immunoglobulin (300 mug) prophylaxis after early miscarriage. METHOD: we included in the study Rh (D) negative blood group patients with positive or unknown Rh (D) partners, who had had a miscarriage up to 12 weeks of gestation, and had been admitted to hospital for uterine curettage. After this procedure 5 ml of venous blood was collected from the patients and the rosette test was applied to screen which patients would need quantitative determination of fetal blood transferred to the maternal circulation, by the Kleihauer-Betke test (K-B). RESULTS: out of 26 patients evaluated the rosette test was positive in one , who showed an FMH of 1.5 ml in the K-B test. CONCLUSIONS: the dose of anti-D immunoglobulin used in cases of miscarriage up to 12 weeks of gestation should be substantially reduced. The availability of preparations of 50 mug is recommended, for a more inexpensive and rational treatment.

The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG) when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women. [ABSTRACT FROM AUTHOR]

Après une fausse couche, l’immunoglobuline anti-D doit être administrée, dans les 72 heures, à toutes les femmes Rhésus négatif. En effet, chez ces femmes, une fausse couche représente une situation à risque d’allo-immunisation fœto-maternelle. La dispensation et l’injection de ce médicament dérivé du sang sont fortement encadrées. [ABSTRACT FROM AUTHOR]

Background: The purpose of this scoping review was to review the literature on healthcare provider provision of anti-D prophylaxis to RhD negative pregnant women in appropriate clinical situations in various healthcare settings. Methods: A scoping review framework was used to structure the process. The following databases were searched: CINAHL (EBSCO), EBM Reviews (OvidSP), Embase (OvidSP), Medline (OvidSP), and Web of Science (ISI). In addition, hand searching of article references was conducted. The search yielded 301 articles. Thirty-five articles remained for review after screening. Two team members reviewed each article using a detailed data collection sheet. A third reviewer was utilized if discrepancies occurred amongst reviewers. Results: The review process yielded 18 included articles. The majority of the studies were conducted in the United Kingdom. Of the 18 studies, 15 were retrospective studies. The articles were largely conducted in one institution. The articles with a focus on routine antenatal provision of anti-D immunoglobulin found that it was given 80 to 90% of the time. Postpartum provision of anti-D immunoglobulin had significantly higher results of 95-100%. The review found that the delivery of anti-D immunoglobulin to RhD negative pregnant women during situations of potential sensitizing events was suboptimal. Conclusions: The included articles examine the management of RhD negative pregnancies in various countries with existing national guidelines. The existing evidence indicates an opportunity for quality improvement in situations where potential sensitizing events are not at routine times in pregnancy, such as miscarriage or fetal demise early in pregnancy. Routine care for the prevention of RhD alloimmunization in pregnancy and postpartum appears to be fairly consistent. The paucity of recent literature in this area leads to a recommendation for further research. [ABSTRACT FROM AUTHOR]

Background: Since its introduction in the 1960s Anti-D immunoglobulin (Anti-D Ig) has been highly successful in reducing the incidence of haemolytic disease of the fetus and newborn (HDFN) and achieving improvements to maternal and fetal health. It has protected women from other invasive interventions during pregnancy and prevented deaths and damage amongst newborns and is a technology which has been adopted worldwide. Currently about one third of pregnant women with the blood group Rhesus D (RhD) negative in the UK (approximately 40,000 women per year in England and Wales), receive antenatal Anti-D Ig in pregnancy when they do not require it because they are carrying a RhD negative fetus. Since 1997, a test using cell free fetal DNA (cffDNA) in maternal blood has been developed to identify the genotype of the fetus and can be used to predict the fetal RhD blood group. Discussion: This paper considers whether it is ethically acceptable to continue administering antenatal Anti-D Ig to all RhD negative women when fetal RHD genotyping using maternal blood could identify those women who do not need this product. Summary: The antenatal administration of Anti-D Ig to a third of RhD negative pregnant women who carry a RhD negative fetus and therefore do not need it raises important ethical issues. If fetal RHD genotyping using maternal blood was offered to all RhD negative pregnant women it would assist them to make an informed choice about whether or not to have antenatal Anti-D Ig. [ABSTRACT FROM AUTHOR]

Background In patients with immune thrombocytopenia (ITP) who are Rhesus (Rh) D positive and who have not undergone splenectomy, the platelet count can be supported by anti-D Ig therapy. The response rate to plasma-derived intravenous anti-D at a dose of 50-75 μg/kg is 70-80% with an increase in platelet count after 24-72 h and duration for more than 21 days in 50% of responders. Rozrolimupab is a mixture of 25 fully human IgG1 recombinant monoclonal anti-D antibodies produced in CHO cells using a single-batch manufacturing strategy from a polyclonal cell bank. Materials & Methods The primary objective of the phase I/II study was to evaluate safety of a single dose in adult RhD-positive non-splenectomized patients with ITP. The secondary objectives were evaluations of the efficacy and appropriate dose for pivotal study. Patients were dosed with a single rozrolimupab dose ranging from 75 to 300 μg/kg, infused intravenously over 15-20 min. Results Rozrolimupab was well tolerated with no unexpected toxicities. The most frequent adverse events were headache, pyrexia, chills and fatigue. Serious adverse events were observed in nine patients, mainly in cohorts treated with doses of 200 μg/kg and 250 μg/kg, but only considered related to rozrolimupab in four patients: decrease in Hb (one patient), extravascular haemolysis (one patient) and transient increase of D-dimers (two patients). Hb decreased by ≥3.0 g/dl in six patients, but decrease by ≥5 g/dl was not observed. Seven patients required blood transfusions. Across all cohorts, 21 of 61 patients (34%) met the response criterion on day 7. The best response was noted in the 300 μg/kg dose cohort with response observed in eight of 13 patients (62%). Median time to response was 2 days and median duration of response was 14 days. Discussion The advantage of rozrolimupab over polyclonal anti-D immunoglobulin is unlimited supply, high and reproducible specificity and activity, and an improved safety profile. Conclusion In conclusion, our data suggest that rozrolimupab is safe, well tolerated and has efficacy similar to plasma-derived anti-D immunoglobulin in the treatment of primary ITP. [ABSTRACT FROM AUTHOR]

Objective To highlight the errors associated with the use of anti- D immunoglobulin in Rh D antigen-negative women, and their resultant clinical impact during and after pregnancy, and to suggest strategies to reduce these errors. Design Retrospective review of cumulative reporting to the UK confidential haemovigilance scheme, Serious Hazards of Transfusion ( SHOT), between 1996 and 2011. Setting Obstetric departments in the UK. Population Mothers who require anti- D immunoglobulin to prevent Rh D sensitisation during pregnancy or after birth. Methods Hospital transfusion teams reported adverse events to the SHOT database. Main outcome measures Reported number of events and their causes, and morbidity and mortality associated with errors. Results In 15 years of reporting, SHOT haemovigilance has shown a total of 1211 errors related to the administration of anti-D immunoglobulin, particularly regarding omission or late administration (157/249 or 63% reported in 2011). Anti-D immunoglobulin errors comprised 13.7% (249/1815) of all SHOT reports in 2011. Failure to recognise women who already have Rh D sensitisation occurred in 19 cases, and was followed by suboptimal monitoring of the pregnancy. Nine of the infants suffered haemolytic disease of the fetus and newborn ( HDFN): one resulted in neonatal death and three required red cell transfusion. Conclusions Babies as well as their mothers remain at risk from avoidable errors. More active attention at national and local levels to further education and training, particularly for midwives, is an absolute necessity. We recommend the use of a SHOT-devised anti- D administration flowchart, adapted locally into a checklist, to help reduce errors. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the efficacy, cost, and effects of anti-D immunoglobulin (anti-D Ig), methylprednisolone, or intravenous immunoglobulin (IVIG) therapy on the development of chronic disease in children who are Rh-positive with diagnosed immune thrombocytopenic purpura (ITP). Children with newly diagnosed ITP and platelet count <20,000/mm were prospectively randomized to treatment with anti-D Ig (50 μg/kg), methylprednisolone (2 mg/kg/day), or IVIG (0.4 g/kg/day, 5 days). Sixty children with a mean age of 6.7 years were divided into three equal groups. No difference was observed between platelet counts before treatment and on day 3 of treatment. However, platelet counts at day 7 were lower in the methylprednisolone group than in the IVIG group ( P = 0.03). In the anti-D Ig group, hemoglobin and hematocrit levels were significantly lower at the end of treatment ( P < 0.05). Chronic ITP developed in 30 % of the anti-D Ig group, 35 % of the methylprednisolone group, and 25 % of the IVIG group, but no significant difference was noted among the groups. The cost analysis revealed that the mean cost of IVIG was 7.4 times higher than anti-D Ig and 10.9 times higher than methylprednisolone. In the treatment of ITP in childhood, one 50 μg/kg dose of anti-D Ig has similar effects to IVIG and methylprednisolone. Among patients who were treated with anti-D Ig, serious anemia was not observed, and the cost of treatment was less than that of IVIG treatment. [ABSTRACT FROM AUTHOR]

Background: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder with a variable clinical course. Methods: A retrospective analysis was carried out of ITP patients presenting to a pediatric hematology-oncology department during a period of 20 years, with a focus on treatment and outcome. Results: One hundred and twenty-four cases were recorded (mean patient age, 8.4 years). Forty-nine children (39.5%) had platelet counts <10 000/µL at diagnosis. No episode of severe bleeding was observed. Peak incidence was observed during spring and summer. Respiratory infections proceeded in 58% of cases. Treatment consisted of i.v. immunoglobulin (IVIG) in 93 children at four dosing schedules. Sixteen children received corticosteroids, 10 children received anti-D immunoglobulin and 14 received no treatment. Recovery was observed in 67% of children on IVIG and in 50% on anti-D globulin. Eight patients did not respond initially and received corticosteroids. Three children with refractory thrombocytopenia received anti-CD20 (rituximab). Fourteen children (11%) had persistent/chronic disease. In 10 of them recovery was observed in 13 months-8 years. Splenectomy was performed in six children with resistant/chronic disease. Conclusion: ITP has a benign course in the majority of cases. Anti-D globulin can effectively be used as an alternative first-line treatment. Rituximab can successfully be used in refractory cases, while splenectomy has currently limited indications. [ABSTRACT FROM AUTHOR]

Objective. We present a pharmacokinetic study evaluating a single intramuscular dose of 250 μg anti-D immunoglobulin in the third trimester of pregnancy. The aim of the study was to determine the kinetic profile and duration of detectable levels of anti-D. Design. Prospective observational study. Setting. Antenatal outpatient clinic. Population. Healthy Rhesus D (RhD)-negative pregnant women with an RHD-positive fetus. Methods. Serial plasma anti-D quantitations following antenatal administration of anti-D immunoglobulin were performed using flow cytometry. Kinetic profiles for anti-D levels were generated from the concentration values at predetermined sampling time points. The half-lives were calculated by linear regression analysis. Main outcome measures. Time vs. concentration profile, half-life and anti-D concentration ≥1 ng/mL close to term. Results. The maximal plasma concentration of anti-D was usually seen at 3-10 days postinjection, with a median value of 25 ng/mL. The half-life varied between individuals, with a median of 23 days. We found detectable levels of anti-D IgG within two weeks of parturition in 11 of 12 women. Conclusions. The preparation of anti-D immunoglobulin used in the present study, if administrated in pregnancy week 28-30, is associated with detectable levels of anti-D in most women at the time of delivery. Although the half-time is 23 days, it is uncertain whether all mothers have adequate anti-D concentrations at term. Alternative strategies may be evaluated in the future, with repeated administration of antenatal prophylaxis at term rather than conventional postpartum administration of anti-D. [ABSTRACT FROM AUTHOR]

Abstract: The preparation anti-D immunoglobulin is an important therapy for both treatment and protection. Titer of anti-D immunoglobulin preparation is an important factor to determine the dose of treatment. Many methods are used to evaluate the titer of anti-D immunoglobulin preparation. One of the new methods developed recently is column agglutination test. To evaluate the BioVue column agglutination test, it was compared to conventional tube agglutination test using anti-D immunoglobulin preparations from three different producers, ten lots each. Results showed that the BioVue column agglutination test is comparable to conventional tube agglutination test but with much ease. In conclusion, the BioVue column agglutination test is accurate and easy to use in determination of anti-D titer for quality control purposes. [Copyright &y& Elsevier]

Background. Despite the introduction of anti-D prophylaxis into clinical practice, RhD alloimmunization still presents a problem to date. The actual incidence of RhD alloimmunization in pregnant women remains unknown in most countries. Anti-D immunoglobulin is administered to RhD negative women at a fixed dose and in much greater amounts than is actually necessary. On the other hand, it is not possible to diagnose cases where greater doses are needed. To optimize the prevention of RhD alloimmunization in RhD negative women, it is important to diagnose conditions that lead to fetomaternal hemorrhage (FMH), precisely determine the volume and subsequently administer the appropriate dose of anti-D immunoglobulin. The possibility to accurately detect FMH and precisely determine its volume would enable more effective and less costly prevention of RhD alloimmunization. Anti-D immunoglobulin could be administered only in indicated cases and only in doses essentially necessary for prevention of RhD alloimmunization. Methods and results. The Cochrane and Up To Date databases of systematic reviews, as well as national guidelines, were reviewed. Conclusions. Due to the medical significance and indispensable economic costs associated with prevention of RhD alloimmunization, it would be appropriate to establish exact methodical guidelines. The text itself should be limited to a list of potentially sensitising events during which anti-D immunoglobulin should be administered to RhD negative women if anti-D antibodies are not already present. Following each potentially sensitising event, the minimal dose of anti-D immunoglobulin necessary for prevention of RhD alloimmunization should be determined. After 20 weeks of gestation, the volume of FMH should also be determined to specify the necessary dose of anti-D immunoglobulin. [ABSTRACT FROM AUTHOR]

Abstract: Morbidity and mortality due to Rhesus antibodies in pregnant women''s serum have steadily declined because of various factors which include, implementation of routine antenatal anti-D prophylaxis and development of non-invasive investigations for monitoring Rhesus affected pregnancies. Because at present this condition is so rare, any case of red-cell alloimmunization should be managed in liaison with a specialist in foetal medicine. Unlike the first immunized pregnancy, maternal antibody titres are not predictive of foetal risk in any subsequent pregnancies. Serial peak middle cerebral artery velocities using Doppler can be used in these pregnancies to detect foetal anaemia. Foetal blood type can now be determined by new techniques to detect free foetal DNA in maternal plasma. In selected cases depending on the gestational age of foetus intrauterine transfusion is necessary through ultrasound directed puncture of the umbilical cord with the direct intravascular infusion of red blood cells. Perinatal survival rates of more than 90% have been reported. [Copyright &y& Elsevier]

The aim of this study was to determine the compliance rates for women being offered routine antenatal anti-D prophylaxis in two obstetric units in the UK. Haemolytic disease of the newborn (HDN) is a potentially serious condition that can result in substantial morbidity and sometimes death. Current guidelines recommend that 500 IU anti-D immunoglobulin G (IgG) should be offered to all non-sensitized RhD-negative women at 28 and 34 weeks’ gestation in order to prevent the risk of RhD sensitization in pregnancy. Implementing guidance, however, remains a challenge. We conducted a retrospective audit of 207 RhD-negative, non-sensitized pregnant women attending obstetric units during 2004 to assess compliance with national guidance on the provision of antenatal anti-D prophylaxis. Informed consent for routine antenatal anti-D prophylaxis was documented for 185 of these women. In total, 86·5% of women received the two doses of anti-D IgG. The majority of women received their first and second doses within 1 week of 28 and 34 weeks’ gestation (87·0 and 86·0%, respectively). Accurate records of prophylactic anti-D IgG were maintained and updated. This audit demonstrates that the level of patient compliance with the two-dose regimen was high. [ABSTRACT FROM AUTHOR]

Background: Chronic idiopathic (immune) thrombocytopenic purpura (ITP) develops in approximately 20% of children with acute ITP. Six years ago, low-dose intravenous immunoglobulin (IVIG) treatment of childhood ITP was started at the Pediatric Hematology Unit, Ain Shams University, while intravenous anti-D has been introduced in Egypt in 2001. Objectives: To assess the efficacy and safety of intravenous anti-D compared to low-dose IVIG in the treatment of children with chronic ITP. Patients and Methods: This randomized trial comprised 34 patients with chronic ITP (18 boys and 16 girls) with recurrent bleeding episodes . Median age of the patients was 6.5 years, duration of thrombocytopenia was >6 months, and platelet count (PC) was <30 × 109/l (30 K). The patient cohort was divided into two subgroups: group A comprised 18 patients treated with anti-D in a dose of 50 μg/kg i.v. initially, and in 12 of them repeated doses (50 μg/kg) were given every 4 weeks, and group B consisted of 16 children who received IVIG in a dose of 250 mg/kg for 2 consecutive days. Bleeding manifestations, complete blood cell and reticulocyte counts were assessed at baseline and 3, 7, 14 and 28 days after infusion. Results: Clinically, more than 80% of the patients (82.3%) showed good control of bleeding. On day 3, 33.3% of group A versus 37.5% of group B, and on day 7: 66.6% of group A versus 75% of group B patients demonstrated a good response (PC >50 K and/or doubling of baseline PC). On days 14 and 21, no significant changes in PCs were observed between both groups. However, only 11.1% of group A and 12.5% of group B patients could maintain PC >100 K on day 28, while 38.8 versus 37.5% of group A and group B, respectively, still had PC ≥ double the initial count. The peak response to anti-D was noticed 7 and 14 days following infusion and to IVIG on days 3 and 7. Repeated doses of anti-D could maintain PC > 50 K (or > double the baseline PC) in 75% of patients 1 week after infusion, and in 60% of them by day 28, with good control of bleeding. Splenectomy was postponed and/or avoided in 4 (33.3%) patients on anti-D maintenance therapy who experienced recurrent severe bleeding episodes before starting therapy. The safety of anti-D was judged by the degree of intravascular hemolysis. The mean hemoglobin decrease was 0.8 ± 0.4 g/dl; in 61.1% of patients the Hb level dropped but none of them experienced a drop of more than 3 g/dl or required transfusion. Conclusion: Both single intravenous anti-D and low-dose IVIG effectively increased PC in children with chronic ITP at risk of bleeding or those with previous bleeding episodes. Repeated doses of anti-D could maintain PC above the critical values or double baseline counts in nearly two thirds of the patients showing good control of bleeding and may serve as an alternative to splenectomy in these patients. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In hepatitis C virus (HCV) infection, serum viral load is important in the prediction of therapeutic efficacy. However, factors that affect the viral load remain poorly understood. To identify viral genomic elements responsible for the viral load, we investigated samples from a population of Irish women who were iatrogenically infected from a single HCV source by administration of HCV 1b-contaminated anti-D immune globulin between 1977 and 1978 (Kenny-Walsh, N Engl J Med 1999; 340: 1228). About 15 patients were divided into two groups, viral load increasing group (11 patients) and decreasing group (4 patients). Pairs of sera were collected from each patient at interval between 1.1 and 5.8 years. Full-length sequences of HCV genome were determined, and analyzed for changes in each patient. Sliding window analysis showed that the decreasing group had significantly higher mutation rates in a short segment of NS5B region that may affect the activity of RNA-dependent RNA polymerase. By comparing each coding regions, significantly higher mutation numbers were accumulated in NS5A region in the increasing group than the decreasing group (0.92 vs 0.16 nucleotides/site/year, P = 0.021). The mutation in certain positions of the HCV genome may be determinant factors of the viral load in a relatively homogeneous patient population. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the pharmacokinetic profile of the new solvent/detergent (S/D) formulation of an anti-D IgG preparation, and to evaluate gender differences. RhD-negative subjects (m/f=10/8) received a single i.m. injection of 250μg anti-D (Partobulin SDF). There was a rapid increase in median anti-D titers over the first 2 days, followed by a plateau from days 2–7. Interestingly, women had a higher maximum concentration (C max) of anti-D and a lower volume of distribution at steady state (V ss) than men. The half-life calculated in this study was 23 days. Thus, results are comparable to published data of the non-S/D treated predecessor product. Because of the observed gender differences in the pharmacokinetics we recommend to pursue the evaluation of sex differences in the pharmacokinetics of other antibodies during early phase drug development. [Copyright &y& Elsevier]

Objective: To determine if the RhD status of the fetus can be detected in an unselected group of RhD-negative women with ongoing pregnancies booking for routine antenatal care. Material and methods: We obtained 2.5ml of whole blood from 202 unselected women with a normal ongoing pregnancy who booked for antenatal care before 20 weeks’ gestation. DNA was extracted and real time quantitative PCR performed. Primers and a specific probe were targeted at the Rhesus D gene. Results: Of 194 women, 31 were RhD-negative with no evidence of prior isoimmunisation. They delivered 17 RhD-positive and 14 RhD-negative babies. Of the 17 RhD-negative women carrying a RhD-positive fetus, the RhD gene was detected in the maternal blood in 14 (82%). There were no false positives. The quantity of RhD gene detected in the maternal blood of RhD-negative mothers ranged from 2×102 to 4×106 copies/ml of whole blood. Conclusion: Using real time quantitative PCR assays to amplify free fetal DNA in the maternal circulation, identification of RhD-positive fetuses in RhD-negative mothers is feasible when they book for antenatal care. Before such RhD genotyping can be introduced into clinical practice, however, further studies are required to show that false negative results can be eliminated and to show that this diagnostic test is reliable outside a research setting. [Copyright &y& Elsevier]