Rh Immunoglobulin Research Articles

RhD-positive red blood cell allocation practice to RhD-negative patients before and during the COVID-19 pandemic.

The red blood cell (RBC) D antigen is highly immunogenic, and anti-D alloimmunization can cause hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. This study examined how RhD-negative patients who required packed RBCs (pRBCs) were handled during the COVID-19 pandemic and whether policies and practices on RhD-positive pRBC allocation to RhD-negative patients changed. The Association for the Advancement of Blood & Biotherapies (AABB) Clinical Hemotherapy Subsection distributed a 17-question survey to physician AABB members to elucidate the impact of the COVID-19 pandemic on the policies and practices governing the provision of RhD-positive pRBCs to RhD-negative patients. There were 215 respondents who started the survey, but only 104 answered all the questions. Most institutional policies (130/155 [83.87%]) and personal practices (100/126 [79.37%]) on pRBC selection did not change during the COVID-19 pandemic. The practice of switching back to RhD-negative pRBCs after administration of RhD-positive pRBCs is variable. More than half of respondents (56/104 [53.85%]) reported offering Rh immunoglobulin to any Rh-negative patients who received RhD-positive pRBCs. Despite RhD-negative pRBC supply challenges, most institutional policies and personal practices on when to provide RhD-positive pRBCs to RhD-negative patients did not change during the pandemic.

Rh sensitization in abortion care: where we've been and where we're going.

The purpose of this review is to summarize the historical context and recent literature that contribute to the debate about preventive strategies for Rhesus (Rh)-alloimmunization in abortion are. Recent studies repeatedly demonstrate that the risk of Rh-alloimmunization in first trimester abortion care is very low. Recent high-quality studies have demonstrated the physiologic presence of fetal red blood cells in maternal circulation even prior to abortion. Thus, establishing the low utility of Rh immunoglobulin prior to abortion before 12 weeks of gestation. There is yet to exist a consensus guideline that balances the desire to prevent a rare devastating outcome and the need to create practical guidelines based on evidence-based risk assessments.

Economic analysis of foregoing Rh immunoglobulin for bleeding in pregnancy

ObjectivesTo perform cost analyses of foregoing RhD blood type testing and administration of Rh immunoglobulin (RhIg) for bleeding in pregnancy at <12 weeks gestation in the United States. Study DesignWe created a decision-analytic model comparing the current standard treatment pathway for patients who have threatened, spontaneous, or induced abortion in the United States, with a new pathway foregoing RhD testing and administration of RhIg for those who are RhD-negative at <12 weeks gestation, assuming that the risk of sensitization is 0%. We derived population and cost estimates from current literature and calculated the number needed to treat, and number needed to screen, to avoid one case of fatal hemolytic disease of the fetus and newborn. We performed sensitivity analyses assuming Rh-sensitization risks of 1.5% and 3% and varying the subsequent pregnancy rates from 44-100%. ResultsThe annual savings to healthcare payers in the United States of foregoing RhD testing and RhIg administration to RhD-negative patients with bleeding events at <12 weeks is $5.5 million/100,000 total pregnancies, assuming that the risk of sensitization is 0%. In the sensitivity analyses with sensitization risk 1.5% and subsequent pregnancy rate 84.3%, foregoing Rh testing and RhIg administration <12 weeks would save $2.8 million/100,000 pregnancies, with a corresponding number needed to treat of 7,322 and number needed to screen of 48,816. At a 3% sensitization rate, the current standard treatment pathway is the most economical. ConclusionsThere is an opportunity to save the United States healthcare payers as much as $5.5 million/100,000 pregnancies by withholding RhIg in specific situations and conserving it for use later in pregnancy. ImplicationsCost analyses support foregoing RhD blood type screening and RhIg administration at <12 weeks gestation if the sensitization rate is <3%. By de-implementing this low value care, payers in the United States can save as much as $5.5 million/100,000 pregnancies and conserve RhIg for use later in pregnancy.

Rare combination of alloantibodies causing hemolytic disease of the newborn – Challenge for identification

Abstract Hemolytic disease of the newborn (HDN) refers to the destruction of the fetal and newborn red cells by maternal red cell antibodies specific for paternally inherited antigens on fetal red cells or erythroid precursors.[1] ABO-incompatibility is the most common cause of HDN. Rh-negative mothers can be alloimmunized with Rh-positive fetus. Prophylactic Rh immunoglobulin use has greatly reduced the HDN due to Rh incompatibility. Alloimmunization can also occur due to other clinically significant minor blood group antigens such as E, c, C, k, KP(a), Js(a), Js(b), Jk(a), Jk(b), Fy(a), Fy(b), S, s, and U. Multiple alloantibodies in mothers’ blood can pose a difficult challenge for identification and finding compatible blood for exchange transfusion. We report a case of HDN due to multiple antibodies and a rare combination of anti-c and anti-Jkb, challenges associated with the identification, confirmation, and finding of compatible blood units.

Fetal RHD Screening in RH1 Negative Pregnant Women: Experience in Switzerland.

RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal RHD genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) only to RH1 negative women carrying a RH1 positive fetus. Data from 30 months of noninvasive fetal RHD screening is presented. Cell-free DNA was extracted from 7192 plasma samples using a commercial kit, followed by an in-house qPCR to detect RHD exons 5 and 7, in addition to an amplification control. Valid results were obtained from 7072 samples, with 4515 (64%) fetuses typed RHD positive and 2556 (36%) fetuses being RHD negative. A total of 120 samples led to inconclusive results due to the presence of maternal or fetal RHD variants (46%), followed by women being serologically RH1 positive (37%), and technical issues (17%). One sample was typed false positive, possibly due to contamination. No false negative results were observed. We show that unnecessary administration of RHIG can be avoided for more than one third of RH1 negative pregnant women in Switzerland. This reduces the risks of exposure to a blood-derived product and conserves this limited resource to women in actual need.

Induced Abortion and the Risk of Rh Sensitization

While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary. To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion. Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion. Induced first-trimester abortion. The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion. Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count. Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.

A cross-sectional study of haemolytic disease of the newborn in Uganda.

Haemolytic disease of the newborn (HDN) is an immune haemolytic anaemia from maternal alloantibodies. Rh immunoglobulin (RhIg) prophylaxis can prevent alloimmunization to the D antigen. However, RhIg is not universally available in Uganda. ABO incompatibility also causes HDN. We determined the prevalence of HDN among newborn infants with jaundice in Uganda. We conducted a prospective cross-sectional study at Kawempe National Referral Hospital, Kampala, Uganda. Infants aged 0-14 days with neonatal jaundice (or total bilirubin >50 μmol/L) were enrolled. Clinical evaluation and laboratory testing, including ABO, RhD typing and maternal antibody screen, were performed. A total of 466 babies were enrolled. The mean (SD) age was 3.4 (1.5) days. Of newborn babies with jaundice, 17.2% (80/466) had HDN. Babies with HDN had lower haemoglobin (SD); 15.7 (2.7) compared with those without HDN; 16.4 (2.4) g/dL, p=0.016; and a higher bilirubin (interquartile range); 241 (200-318) compared with those without HDN; 219 (191-263) μmol/L, p < 0.001. One baby had anti-D HDN, while 46/466 had HDN from an ABO incompatibility (anti-A 43.5% and anti-B 56.5%); 82% of babies with HDN also had suspected neonatal sepsis or birth asphyxia. About 79.2% (57/72) of mothers did not have ABO/Rh blood group performed antenatally. All infants with HDN survived except one. Among newborn infants with jaundice, HDN is not rare. The majority is due to ABO HDN affecting group A and group B babies equally. Ensuring routine ABO/Rh grouping for all pregnant women is an area for improvement.

Routine noninvasive prenatal screening for fetal Rh D in maternal plasma-A 2-year experience from a single center in Belgium.

Hemolytic disease of the fetus and newborn (HDFN) due to rhesus D (RhD) immunization is a potentially life-threatening situation for which use of Rh Immunoglobulin (RhIg) has decreased risk drastically. Determination of fetal RHD on maternal plasma can be used to restrict prenatal RhIg administration to women carrying an RhD-positive child, avoiding unnecessary administration of blood-derived products. The aim of this study is to determine the performance of fetal RHD typing in our center. We prospectively collected 205 fetal RHD and 127 serological cord blood RhD data from RhD-negative women starting at 11 weeks of pregnancy (from October 2019 to October 2021). Real-time polymerase chain reaction targeting RHD exon 5 and 7 was used, similar to the screening program in The Netherlands, supplemented with an amplification control (beta-actin; ACTB) and a sex determination marker located on the Y-chromosome (SRY gene). Fetal RHD testing reached a sensitivity and specificity of 100%. No false-negative nor false-positive results were reported. Inconclusive results (6%, 13/205) were due to weak amplification in 10 cases, a maternal RHD variant in 2 cases (RHD*01N.71 and partial DVI), and a fetal RHD variant (partial DVI) in 1 case. Unnecessary administration of RhIg prophylaxis was avoided in 33% of cases and on the other hand was administered in one case (fetal partial DVI) which would have been missed with cord blood serology. This study demonstrates the high accuracy of routine prenatal fetal RHD gene screening after 11 weeks of pregnancy, encouraging routine clinical practice.

Cost-effectiveness of noninvasive fetal RhD blood group genotyping in nonalloimmunized and alloimmunized pregnancies.

We sought to determine the cost-effectiveness of noninvasive fetal RhD blood group genotyping in nonalloimmunized and alloimmunized pregnancies in Canada. We developed two probabilistic state-transition (Markov) microsimulation models to compare fetal genotyping followed by targeted management versus usual care (i.e., universal Rh immunoglobulin [RhIG] prophylaxis in nonalloimmunized RhD-negative pregnancies, or universal intensive monitoring in alloimmunized pregnancies). The reference case considered a healthcare payer perspective and a 10-year time horizon. Sensitivity analysis examined assumptions related to test cost, paternal screening, subsequent pregnancies, other alloantibodies (e.g., K, Rh c/C/E), societal perspective, and lifetime horizon. Fetal genotyping in nonalloimmunized pregnancies (at per-sample test cost of C$247/US$311) was associated with a slightly higher probability of maternal alloimmunization (22 vs. 21 per 10,000) and a reduced number of RhIG injections (1.427 vs. 1.795) than usual care. It was more expensive (C$154/US$194, 95% Credible Interval [CrI]: C$139/US$175-C$169/US$213) and had little impact on QALYs (0.0007, 95%CrI: -0.01-0.01). These results were sensitive to the test cost (threshold achieved at C$88/US$111), and inclusion of paternal screening. Fetal genotyping in alloimmunized pregnancies (at test cost of C$328/US$413) was less expensive (-C$6280/US$7903, 95% CrI: -C$6325/US$7959 to -C$6229/US$7838) and more effective (0.19 QALYs, 95% CrI 0.17-0.20) than usual care. These cost savings remained robust in sensitivity analyses. Noninvasive fetal RhD genotyping saves resources and represents good value for the management of alloimmunized pregnancies. If the cost of genotyping is substantially decreased, the targeted intervention can become a viable option for nonalloimmunized pregnancies.

Prophylaxis of rhesus-sensitization of pregnant women. Experience of anti-rhesus immunoglobulin Rhesogam® N using

Aim. Retrospective assessment of the efficiency and safety of the anti-rhesus Rh (D) immunoglobulin Rhesogam N in preventing isoimmunization in Rh-negative women during pregnancy.&#x0D; Materials and methods. An analysis of medical records of 196 Rh-negative patients who received anti-Rh immunoglobulin Rhesogam N in the period 20192021 was performed. The indications for the drug were the aspiration of chorionic villi, amniocentesis and prenatal prophylaxis in women with negative level of anti-Rh antibodies and in the case of Rh-positive husbands.&#x0D; Results. In total, 227 doses of the anti-rhesus immunoglobulin Rhesogam N were administered, including those women who underwent invasive procedures (aspiration of chorionic villi, amniocentesis). There were no adverse events, including anaphylaxis or drug-related events. 172 rhesus-positive babies were born. No cases of hemolityc disease of the newborns were reported. Anti-Rh antibodies were not found in their mothers after childbirth.&#x0D; Conclusion. The study confirmed the efficacy and safety of the antiresus Rh (D) immunoglobulin Rhesogam N for the prevention of Rh isoimmunization.

RHD Genotypes in a Chinese Cohort of Pregnant Women.

RHD variants in D¯ Chinese pregnant women arose difficulties in management during pregnancy. Therefore, this study aims to precisely manage D¯ pregnant women by evaluating the spectrum of RHD mutations in D¯ pregnant women and getting insight into the possible rare alleles of RHD. A total of 76 D¯ pregnant women were analyzed by performing polymerase chain reactions with sequence-specific primers (PCR-SSP), the 10 RHD exons Sanger sequencing, RHD zygosity detection, and mRNA sequencing (mRNA-seq). About 40% of alleles are variations of RHD, including RHD 1227A homozygous, RHD-CE(2-9)-D, et al. Therefore, we developed a molecular diagnostic strategy for Chinese women, and most D¯ pregnant women can be diagnosed with this simple decision tree. After RHD genotyping for D¯ pregnancy women, we eliminated at least 15% unnecessary ante- and postpartum injections of Rh immunoglobulin (RhIG). As the first pedigree study and the first functional analysis under physiological conditions, mRNA-seq revealed that c.336-1G>A mutation mainly led to the inclusion of the intron 2, which indirectly explained the D¯ phenotype in this family. We also developed a robust protocol for determining fetal RhD status from maternal plasma. All 31 fetuses were predicted as RhD positive and confirmed the RhD status after birth.

143 Rh-Disease Awareness and Prevention (RhAP): Knowledge Assessment of Obstetrical Patients

Abstract Primary Subject area Maternal-Fetal Medicine Background Rhesus hemolytic disease of the newborn (RhD) was once the most common and severe form of hemolytic disease of the newborn with outcomes including anemia, jaundice, stillbirth and death. Approximately 15% of Canadian women are Rh-negative, yet RhD is relatively unknown due to prevention by Rh immunoglobulin (RhIG). There is a need to advocate for the ongoing prevention of RhD in high-income countries (HICs) due to low incidence, vaccine hesitancy and misinformation, and in low-income countries (LICs) where lack of access to RhIG contributes to over 350,000 annual cases worldwide. Objectives Our present aim is to assess the current state of knowledge of RhD among women in our centre. Design/Methods Questionnaires were administered to a consecutive sample of pregnant women of all blood types (5-42 weeks gestation) attending an urban Obstetrics Clinic between January - March 2020, and included demographics and self-reporting of current RhD awareness. Results Of the 586 participants surveyed, 43% did not know their blood type and 16% identified as Rh-negative (Table 1). Sixty-one percent of participants recalled receiving information about their blood type, and only 31% knew their partner’s blood type. Only 45% of the Rh-negative subset (Table 2) in their third trimester (or postpartum) knew that they had been given RhIG (routinely offered at 28 weeks gestation). While 84% of Rh-negative women had received information about RhD from various sources (physician, online, etc.), there was a lack of depth in their knowledge with two-thirds having no knowledge of the common sequelae of RhD. The majority of Rh-negative participants expressed interest in contributing to local efforts (58/92), including interest in our advocacy group. Conclusion As expected, many participants did not know their Rh status, despite routine testing in pregnancy. Many were unaware of the potential sequelae associated with RhD and rationale for its prevention, even in the Rh-negative subgroup. Not all Rh-negative women were aware of having received RhIG, presumably having received it without knowledge or understanding. We are concerned that lack of awareness, especially among Rh-negative women in HICs may lead to increased complacency, RhIG refusal, and missed opportunities for patient self-advocacy. Our questionnaire results provide further impetus to advocate for increased RhD education for the patients and their care providers. Next steps include the creation of a patient-led focus group that aims to improve local and global awareness of RhD to help decrease the burden of this potentially devastating and preventable disorder.

A window of opportunity: systems thinking for prevention of haemolytic disease of the fetus and newborn with transfusion policy.

A window of opportunity: systems thinking for prevention of haemolytic disease of the fetus and newborn with transfusion policy.

Proportion of Unsensitized Rh(D)-Negative Pregnant Women Delivered at Siriraj Hospital Who Received a Complete Course of Anti-D Immunoglobulin: An Awareness problem?

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. Keywords: Rh(D)-negative, Alloimmunization, Anti-D immunoglobulin, Anti-D prophylaxis, Rh immunoglobulin

Rhesus disease in Brazil: A multi-professional national survey

Universal prenatal Rhesus (Rh) screening and prophylaxis with Rh immunoglobulin have been highly effective practices for preventing neonatal morbidities and mortality. However, there has been an enormous failure to prevent Rh sensitization and its adverse consequences worldwide, especially in low- and middle-income countries (LMICs). Brazil is the largest South American country with an upper-middle-income economy, but has regional inequalities in maternal and newborn care and no national or regional reporting about Rh sensitization. We performed a national survey of multi-healthcare professionals using a closed social media group and demonstrated that Rh disease is present in the country with significant knowledge heterogeneity among professionals and regions. Proper education and training across Brazil are needed to fully eradicate the disease and reduce mortality and long-term disabilities related to neonatal hyperbilirubinemia.

Infants affected by Rh sensitization: A 2-year Canadian National Surveillance Study.

Rh sensitization occurs when Rh(D)-negative women develop anti-Rh(D) antibodies following exposure through pregnancy or transfusion. Rh disease may cause jaundice, anemia, neurological impairment, and death. It is rare in countries where Rh Immune Globulin (RhIg) is used. Canadian Rh sensitization and disease rates are unknown. This survey-based study was conducted using a Canadian Paediatric Surveillance Program questionnaire sent to Canadian paediatricians and paediatric subspecialists to solicit Rh disease cases from May 2016 to June 2018. Paediatricians reported Rh-positive infants ≤ 60 days of age, born to Rh-negative mothers with RhD sensitization. Sixty-two confirmed cases of infants affected by Rh(D) sensitization were reported across Canada. The median gestational age of neonates was term, age at presentation was 2 hours, and hemoglobin at presentation was 137.5 g/L (33 to 203 g/L). The median peak bilirubin and phototherapy duration were 280 µmol/L (92 to 771 µmol/L), and 124 hours, respectively. Thirty (48%) infants received Intravenous immune globulin (IVIG) (median two doses). Seventeen (27%) received one to three simple transfusions; 10 (16%) required exchange transfusions. Six (10%) infants presented with acute bilirubin encephalopathy, and less than five presented with seizures. Fourteen mothers with affected infants were born outside of Canada. Rh disease continues to exist in Canada. Additional efforts are needed to raise awareness of Rh disease, prevent disease, and minimize sequelae when it does occur. The ongoing global burden of Rh Disease, as well as the possibility of emerging Rh immunoglobulin refusal are among factors that could be taken into consideration in future prevention efforts.

The concentration of fetal red blood cells in first-trimester pregnant women undergoing uterine aspiration is below the calculated threshold for Rh sensitization

ObjectivesTo calculate the minimum fetal red blood cell concentration required to cause maternal Rh sensitization; validate the use of a flow cytometry protocol below that concentration; preliminarily assess the concentrations of fetal red blood cells in pregnant women before and after uterine aspiration. Study designUsing pre-existing literature, we calculated the lowest concentration of fetal red blood cells found to cause sensitization within adult female circulation. We validated a two-color flow cytometry protocol using fluorescently labeled antibodies to Hemoglobin F (expressed by fetal red blood cells and adult F cells) and Carbonic Anhydrase (expressed in red blood cells during the third trimester and postnatally) by titrating second trimester cord blood into non-pregnant adult blood. We applied this flow cytometry protocol in a prospective cohort study of 42 pregnant women at 5–12 weeks gestational age undergoing uterine aspiration for induced or spontaneous abortion. ResultsThe calculated threshold for causing Rh sensitization was 250 fetal red blood cells per 10 million total red blood cells. We showed a linear relationship between observed and expected fetal red blood cell fractions in titrated samples. Fetal red blood cell counts were more reliable when samples acquired by flow cytometry contained at least 1 million red blood cells. All 37 subjects with evaluable paired samples demonstrated fetal red blood cell concentrations below the calculated threshold for Rh sensitization both pre- and post-procedure. The fetal RBC concentrations increased from a mean of 4.5 (median 0, range 0–57) fetal RBCS pre- to a mean of 8.6 (median 2, range 0–32) fetal RBCs post- per 10 million total RBCs (p < 0.001). ConclusionsFlow cytometry was capable of separately quantifying fetal red blood cells and maternal F cells to very dilute concentrations. Fetal red blood cell exposure in the first trimester was well below the calculated threshold for maternal Rh sensitization in our cohort. Larger studies are warranted to confirm our pilot study findings, fill this evidence gap and inform universal guidelines for administering Rh immunoglobulin after first trimester uterine aspiration. ImplicationsFetal red blood cell exposure following first trimester uterine aspiration is well below the calculated threshold for maternal Rh sensitization in our cohort.

A multi-centre study on the performance of the molecular genotyping platform ID RHD XT for resolving serological weak RhD phenotype in routine clinical practice.

There is concern regarding the lack of prevention of unnecessary transfusion of RhD negative red cells and unnecessary administration of Rh immunoglobulin (RhIG) to pregnant women. In this study, performance of ID RHD XT, a genotyping assay for identification of six RHD allelic variants and human platelet antigens HPA-1a/1b was assessed. Whole blood samples presenting weak, discrepant or inconclusive D phenotype results were genotyped with ID RHD XT and compared to reference molecular tests. Candidacy for RhIG prophylaxis was determined by analysing samples from pregnant women. Hands-on time to complete the procedures was measured. Overall, 167 samples were tested (55 donors, 56 patients, 52 pregnant women and four newborns). Agreement between ID RHD XT and the reference method was 100% (51% weak D type 1, 2 or 3; 35·5% weak D Types 1, 2 or 3 not detected; 4% RHD deletion; 1% RHD*Pseudogene; 1% RHD*DIIIa-CE(3-7)-D; and 4% no amplification variant detected for RHD genotype; and 64% HPA-1a/a; 30% HPA-1a/b; and 3% HPA-1b/b for HPA-1 genotype). Call rate was 98·2%. ID RHD XT identified 40% of the pregnant women that would not have required RhIG prophylaxis. Overall hands-on time was 25-45min to process a batch of 24 samples, and four hours for total assay time. ID RHD XT yielded reproducible results for RHD typing in serologically weak D phenotype individuals. ID RHD XT was proven useful for the correct management of patients with RhD serological discrepancies and the rational use of RhIG in pregnancy.

A successful pregnancy occurred after isolating the offending antibody(s) and choosing appropriate sperm donor of similar phenotype

Sensitization against Rh(D )is the most common cause of haemolytic disease of fetus and newborn (HDFN). Now a days, a widespread use of antenatal and postnatal Rh immunoglobulin has resulted in marked decrease in prevalence of Rh(D) alloimmunization. Fetal loss due to other red cell antigens gain importance as there are no prophylactic immunoglobulin are available. Here, we present a case of primary infertility associated with non Rh(D) alloimmunization which was detected in a 30 year old housewife during her ongoing infertility treatment. The antibody identification workup showed patient is having multiple alloantibodies , probable anti-c, and anti-Fya. The extended phenotype shows that the husband is mismatched with the wife's phenotype in “c” and Fya. Also the probable antibody in the mother's serum are anti-c and anti-Fya which are noted to cause HDFN as per literature.

Haemolytic disease of the fetus and newborn: advancements in precision and prevention

In pregnant patients, the impact of blood type and the presence of red blood cell antibodies influence the course of the pregnancy and the health of the fetus and newborn infant. Throughout history, haemolytic disease of the fetus and newborn has played a fundamental role in the discovery of the blood group antibodies and their cognate antigens. The mid‐1900s were noted for the advent of Rh immunoglobulin. Now, the technological advancements in diagnosis and treatment of haemolytic disease of the fetus and newborn have provided the critical tools needed to support mothers with affected pregnancies. The knowledge of blood typing has been further refined with the explosion of understanding about blood group genes, particularly in the RH blood group. Genomic blood group typing, improvements in ultrasound technology and transfusion medicine progress have advanced the field. The care of women with potentially affected pregnancies has never been more robust. Despite this, the risk to the fetus is significant, and prevention strategies for maternal alloimmunization deserve continued attention.