Immune interactions and regulation with CD39+ extracellular vesicles from platelet concentrates.

Introduction: CD39 plays an important role in the immunoregulation and inhibition of effector cells. It is expressed on immune cells, including Tregs, and on extracellular vesicles (EVs) budding from the plasma membrane. Platelet transfusion may induce alloimmunization against HLA-I antigens, leading to refractoriness to platelet transfusion with severe consequences for patients. Tregs may play a key role in determining whether alloimmunization occurs in patients with hematologic disorders. We hypothesized that CD39+ EVs might play an immunoregulatory role, particularly in the context of platelet transfusions in patients with hematologic disorders. Such alloimmunization leads to the production of alloantibodies and is sensitive to the regulatory action of CD39. Methods: We characterized CD39+ EVs in platelet concentrates by flow cytometry. The absolute numbers and cellular origins of CD39+ EVs were evaluated. We also performed functional tests to evaluate interactions with immune cells and their functions. Results: We found that CD39+ EVs from platelet concentrates had an inhibitory phenotype that could be transferred to the immune cells with which they interacted: CD4+ and CD8+ T lymphocytes (TLs), dendritic cells, monocytes, and B lymphocytes (BLs). Moreover, the concentration of CD39+ EVs in platelet concentrates varied and was very high in 10% of concentrates. The number of these EVs present was determinant for EV-cell interactions. Finally, functional interactions were observed with BLs, CD4+ TLs and CD39+ EVs for immunoglobulin production and lymphoproliferation, with potential implications for the immunological management of patients.

A genome-wide association study of alloimmunization in the TOPMed OMG-SCD cohort identifies a locus on chromosome 12.

BACKGROUND: Red cell alloimmunization after exposure to donor red cells is a very common complication of transfusion for patients with sickle cell disease (SCD), resulting frequently in accelerated donor red blood cell destruction. Patients show substantial differences in their predisposition to alloimmunization, and genetic variability is one proposed component. Although several genetic association studies have been conducted for alloimmunization, the results have been inconsistent, and the genetic determinants of alloimmunization remain largely unknown. STUDY DESIGN AND METHODS: We performed a genome-wide association study (GWAS) in 236 African American (AA) SCD patients from the Outcome Modifying Genes in Sickle Cell Disease (OMG-SCD) cohort, which is part of Trans-Omics for Precision Medicine (TOPMed), with whole-genome sequencing data available. We also performed sensitivity analyses adjusting for different sets of covariates and applied different sample grouping strategies based on the number of alloantibodies patients developed. RESULTS: We identified one genome-wide significant locus on chr12 (p = 3.1e-9) with no evidence of genomic inflation (lambda = 1.003). Further leveraging QTL evidence from GTEx whole blood and/or Jackson Heart Study PBMC RNA-Seq data, we identified a number of potential genes, such as ARHGAP9, STAT6, and ATP23, that may be driving the association signal. We also discovered some suggestive loci using different analysis strategies. DISCUSSION: We call for the community to collect additional alloantibody information within SCD cohorts to further the understanding of the genetic basis of alloimmunization in order to improve transfusion outcomes.

Anti-Jk-b Antibodies and Hemolytic Disease of the Fetus and Newborn: Case-Based Learning.

The Kidd blood group is clinically significant as Kidd antibodies have the potential to trigger both acute and delayed transfusion reactions, along with hemolytic disease of the fetus and newborn (HDFN). Here, we have reported a case of HDFN due to Jk-b antibodies. A 31-year-old pregnant female was found to have Jk-b antibodies on screening with the Bio­Rad ID Dia 11-cell panel (Bio-Rad Laboratories, Inc., CA) after her cross-matching results were incompatible. Emergency lower segment caesarian section was done; the baby was non-hydropic at birth with an increase in bilirubin that required high-intensity phototherapy. HDFN resulting from anti-Jk-b incompatibility is rare and tends to present with mild clinical symptoms and a favorable prognosis. However, monitoring of antibody titers is essential to prevent potentially fatal complications. Additionally, antenatal antibody screening should be mandatory for all pregnant women, regardless of their Rh-(D) antigen status, to detect red cell alloimmunization to other clinically significant blood group antigens.

Prevalence of unexpected red blood cell antibodies in pregnant women and follow-up of pregnancy outcome in pregnant women treated with intra-uterine transfusion.

BACKGROUND: For the management of hemolytic disease of the fetus and newborn (HDFN), it is important to detect unexpected red cell antibody in pregnant women. We assessed the prevalence of unexpected red cell antibodies in consecutive pregnant women attending antenatal clinic (ANC). More importantly, cases with unexpected antibody causing severe anemia were followed-up for intervention (Intra-uterine transfusion {IUT}) and outcome of pregnancy (still-birth/live-healthy). AIMS AND OBJECTIVES: The study was conducted with an objective to find the prevalence of unexpected RBC antibodies in pregnant women, their specificity and to do the follow-up for IUT and outcome of pregnancy (still-birth, live-birth) in antibody positive women. MATERIALS AND METHODS: This was a prospective study from January 2021 to May 2022 at two tertiary care centres. All antenatal samples received by the laboratory were screened for unexpected red cell antibody. Whenever antibody screen was positive, antibody identification was performed. Patients, positive for unexpected antibody and anemia were followed up for any transfusion-based intervention and outcome of pregnancy. RESULTS: A total of 539 consecutive samples were worked up and among these, 10 samples (1.85%) were found to be antibody positive. The antibodies identified were Anti-D (n=6), anti-Leb (n=1), anti-M (n=1), anti-C (n=1) and anti-E (n=1).The prevalence of unexpected antibodies in Rh positive and Rh negative pregnant women was 0.83% and 10.9% respectively. Follow-up was done for all 10 cases with unexpected antibody and anemia was monitored by MCA PSV (middle cerebral artery peak systolic velocity).Two women developed severe anemia thus requiring single intrauterine transfusion (at 26 weeks and 28 weeks respectively) each, for correction of anemia. In both these cases, healthy male child was delivered. At 3-month follow-up both children were alive and healthy. CONCLUSION: The study found prevalence of unexpected RBC antibodies in pregnant women as 1.85%. The study also underlined importance of transfusion-based interventions contributing to successful outcome in couple of cases with severe anemia.

The Distribution Patterns of Rhesus (Rh) Antigens.

INTRODUCTION: The determination of one's blood group is dictated by the inheritance-based diversity in the presence or absence of RBC antigens on the surface. Extended Rhesus (Rh) antigens are the most clinically relevant antigens of blood group systems after the ABO blood group system in transfusion medicine. The aim of this study was to serologically assess the prevalence of extended Rh antigens across diverse blood group systems. METHODS: A total of 2043 samples were tested for the ABO blood group and Rh typing with monoclonal antisera. The Rh phenotyping (C, c, E, e ) was performed on all the samples. RESULTS: The most frequently observed ABO blood group was O (36.5%), while AB (13.6%) was identified as the least prevalent. Positive Rh D antigen was found in 91.6% of tested samples, while 8.4% were Rh D-negative. The most frequently encountered antigen was e, followed by D, while the least prevalent was E. DISCUSSION: Establishing a Rh phenotype repository for blood donors and conducting Rh phenotype assessments as part of pretransfusion testing before initiating the initial blood transfusion for each patient could significantly lower the patients' incidence of alloimmunization.

Maternal isoimmunization associated fetal anemia: A case report.

Maternal isoimmunization occurs when a pregnant woman develops an immune reaction due to the inheritance of a red-cell antigen, which is paternally derived and can result in fetal anemia, hemolysis, fetal death, and hydrops fetalis as the antibodies might travel through the placenta and get adhered to the antigens present in the erythrocytes of the fetus. This report highlights a rare case of Rh isoimmunization leading to fetal anemia in a 26-year-old female and evaluates the impact of intrauterine transfusion (IUT) in terms of the gestational age at delivery along with the mode of delivery, procedural complications, and overall survival rate of the fetus. In conclusion, the most frequent cause of fetal anemia is Rh alloimmunization, which should be taken into consideration while making a differential diagnosis throughout the assessment. Improvements in IUT procedures and earlier detection of the MCA-PSV by Doppler ultrasonographic examination have also contributed to better results.

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

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

Red Blood Cell Alloimmunization in Pregnancy: A Review of the Pathophysiology, Prevalence, and Risk Factors.

This review paper provides an overview of the risk factors and laboratory testing for red blood cell (RBC) alloimmunization in pregnancy. RBC alloimmunization is a significant medical issue that can cause haemolytic disease of the fetus and newborn (HDFN), leading to neonatal morbidity and mortality. Current HDFN prophylaxis targets only Rhesus D (RhD) alloimmunization, with no effective measures to prevent alloimmunization to other RBC antigen groups. Several factors can increase the risk of developing RBC alloimmunization during pregnancy, including fetomaternal haemorrhage, RBC and maternal genetic status, and previous transfusions. Identifying these risk factors is essential to execute the appropriate management strategies to minimize the risk of HDFN. The review also discusses the laboratory methods and overview of pregnancy management. The paper highlights the importance of identifying and managing the risk factors for RBC alloimmunization in pregnancy to minimize the risk of HDFN and improve neonatal outcomes.

How anti-c in a D- patient prompted lifesaving work between a transfusion service and a blood center reference laboratory.

This case report showcases an extraordinary collaboration to support the transfusion needs of a patient with a rare phenotype and long-standing anemia due to gastrointestinal bleeding. This report describes the Immunohematology Reference Laboratory testing and logistics of rare blood provision over an 11-year period, as well as a summary of the hematologic, gastroenterologic, and surgical interventions. This case illustrates how a strong collaboration among the clinical team, laboratory, blood center, and the rare donor community facilitated successful management of this patient's anemia until the patient could receive life-changing treatment.

Successful management of maternal anti-PP1Pk alloimmunization in pregnancy with therapeutic plasma exchange and intravenous immunoglobulin.

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.

Meeting the transfusion needs of a patient with anti-Ena requires an international effort.

This extraordinary case showcases the identification of a rare anti-Ena specificity that was assisted by DNA-based red blood cell antigen typing and collaboration between the hospital blood bank in the United States, the home blood center in Qatar, the blood center Immunohematology Reference Laboratory, as well as the American Rare Donor Program (ARDP) and the International Society for Blood Transfusion (ISBT) International Rare Donor Panel. Ena is a high-prevalence antigen, and blood samples from over 200 individuals of the extended family in Qatar were crossmatched against the patient's plasma with one compatible En(a-) individual identified. The ISBT International Rare Donor Panel identified an additional donor in Canada, resulting in a total of two En(a-) individuals available to donate blood for the patient.

Transfusion Support in Hematopoietic Stem Cell Transplantation: A Contemporary Narrative Review.

Hematopoietic stem cell transplantation (HSCT) is a cornerstone of modern medical practice, and can only be performed safely and effectively with appropriate transfusion medicine support. Patients undergoing HSCT often develop therapy-related cytopenia, necessitating differing blood product requirements in the pre-, peri-, and post-transplant periods. Moreover, ensuring optimal management for patients alloimmunized to human leukocyte antigens (HLA) and/or red blood cell (RBC) antigens, as well as for patients receiving ABO-incompatible transplants, requires close collaboration with transfusion medicine and blood bank professionals. Finally, as updated transfusion guidelines and novel blood product modifications emerge, the options available to the transplant practitioner continue to expand. Herein, we detail contemporary blood transfusion and transfusion medicine practices for patients undergoing HSCT.

Disease severity in subsequent pregnancies with RhD immunization: A nationwide cohort.

BACKGROUND AND OBJECTIVES: To evaluate the severity of haemolytic disease of the foetus and newborn (HDFN) in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease. MATERIALS AND METHODS: Nationwide prospective cohort study, including all pregnant women with RhD antibodies. All women with at least two pregnancies with RhD antibodies and RhD-positive foetuses were selected. The main outcome measure was the severity of HDFN in the first and subsequent pregnancy at risk. A subgroup analysis was performed for the group of women where RhD antibodies developed after giving birth to an RhD-positive child and thus after receiving anti-D at least twice (group A) or during the first pregnancy at risk for immunization (group B). RESULTS: Sixty-two RhD immunized women with a total of 150 RhD-positive children were included. The severity of HDFN increased for the whole group significantly in the subsequent pregnancy (p < 0.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, after giving birth to an RhD-positive child (group A), severe HDFN in the next pregnancy was uncommon (22%). Especially when no therapy or only non-intensive phototherapy was indicated during the first immunized pregnancy (6%) or if the antibody-dependent cell-mediated cytotoxicity result remained <10%. Contrarily, women with a negative first trimester screening and RhD antibodies detected later during the first pregnancy of an RhD-positive child (group B), often before they had ever received anti-D prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%). CONCLUSION: RhD-mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of an RhD-positive child are at highest risk of severe disease in the next pregnancy.

Non-RhD alloimmunization in pregnancy: an updated review.

RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be associated with the occurrence of this phenomenon and that have been growing in proportion, given that current prevention strategies focus only on anti-RhD antibodies. Although not widespread, the screening and diagnostic management of the disease caused by these antibodies has recommendations in the literature. For this reason, the following review was carried out with the objective of listing the main red blood cell antigen groups described - such as Rh, ABO, Kell, MNS, Duffy, Kidd, among others - addressing the clinical importance of each one, prevalence in different countries, and recommended management when detecting such antibodies during pregnancy.

The influence of HLA allele and haplotype on RhE alloimmunization among pregnant females in the Chinese Han population.

BACKGROUND AND OBJECTIVES: Anti-E alloantibody is the most common and important red blood cell (RBC) alloantibody during pregnancy. The study aimed to determine the correlation between RhE alloimmunization and human leukocyte antigen (HLA) allele polymorphism, as well as haplotype diversity, among pregnant individuals in the Chinese Han population. STUDY DESIGN AND METHODS: All individuals included in our study were RhE-negative pregnant women of Chinese Han ethnicity, confirmed through serological testing. Pregnancy could be the only potential stimulating factor in RBC alloimmunization. Given the serological testing, the participants were divided into anti-E (responders) and non-anti-E-producing group (non-responders). The class I and II classical HLA genotyping were determined using next-generation sequencing, and the HLA genotype and haplotype frequencies were compared between the responders and non-responders. RESULTS: In total, 76 responders and 94 non-responders were enrolled in this study. Comparison results showed that all HLA class I alleles had no difference between the two groups. For HLA class II phenotypes, responders had higher frequencies of HLA-DRB1*09:01, HLA-DQA1*03:02 and HLA-DQB1*03:03 phenotypes than non-responders, and the differences were statistically significant (pc < 0.05). In addition, the haplotype frequency of HLA-DRB1*09:01-DQA1*03:02-DQB1*03:03 in the RhE responders was significantly higher than in the non-responders (31.58% vs. 12.77%; odds ratio, 3.154; 95% confidence interval, 1.823-5.456; pc value, 1.25 × 10-3). CONCLUSION: Our findings indicated that HLA-DRB1*09:01, HLA-DQA1*03:02 and HLA-DQB1*03:03 might be susceptible alleles for RhE alloimmunization among Chinese Han pregnant females. These three susceptible alleles constituted the unique three-locus haplotype in the RhE responders and collaborated to RhE alloimmunization.

Anti-D Alloimmunization Following Rhesus-Incompatible Platelet Transfusion in a Myelodysplastic Syndrome Patient.

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

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

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

Intrauterine Transfusion for Rhesus Alloimmunization: A Historical Retrospective Cohort from A Single Reference Center in Brazil.

Objective: This study aimed to describe the historical experience of a single reference center in Brazil with intrauterine transfusion (IUT) for Rhesus (Rh) alloimmunization, evaluating the major complications and the perinatal outcomes of this procedure. Methods: This retrospective cohort study evaluated data from medical records of pregnant women between 20 and 34 weeks of gestation whose fetuses underwent IUT by cordocentesis between January 1991 and June 2021. The same experienced examiner performed all procedures. Univariate and multivariate logistic regression was used to assess the effect of fetal hydrops, duration of IUT, post-transfusion cord bleeding time, and bradycardia on death (fetal or neonatal). Results: We analyzed data from 388 IUTs in 169 fetuses of alloimmunized pregnant women with a mean age of 29.3 ± 5.1 years. Death and fetal hydrops were significantly associated at first IUT (p < 0.001). We had two cases of emergency cesarean section (mean of 0.51% per IUT) and three cases of premature rupture of the ovular membranes (mean of 0.77% per procedure). Thirty-six deaths were recorded, including 14 intrauterine and 22 neonatal. A higher percentage of neonatal deaths was observed in the group with post-transfusion cord bleeding time > 120 s (45.8%). The odds of neonatal death were 17.6 and 12.9 times higher in cases with hydrops and bradycardia than in cases without hydrops and bradycardia, respectively. The odds of death (fetal and neonatal) were 79.9 and 92.3 times higher in cases with hydrops and bradycardia than in cases without hydrops and bradycardia, respectively. Conclusions: The most common complications of IUT for Rh alloimmunization were post-transfusion cord bleeding, fetal bradycardia, premature rupture of ovular membranes, and emergency cesarean section. The IUT complication most associated with death (fetal and neonatal) was bradycardia, and the perinatal outcomes were worse in fetuses with hydrops.

Two Cases of Anti-D Alloimmunization in D-Negative Thai Patients as a Result of the Asian-Type DEL on Transfused Red Cells.

Introduction: DEL is known to be one of the weakest D variants, which can be detected by the adsorption-elution technique or by molecular study. Currently, in Thailand, we do not routinely test for DEL variants serologically or genetically among serologic RhD-negative blood donors. Case Presentation: We reported 2 cases of alloimmunization after transfused with Rh DEL, RHD*DEL1 allele, in the Thai population. The first case was a 73-year-old male with anemia who presented with post-cardiac arrest and septic shock. The patient was group B, RhD-negative, and was transfused with RhD-negative red blood cells (RBCs). Antibody screening and identification found that the patient developed anti-D and anti-Mia during the admission course. The second case was a 38-year-old woman with pseudomyxoma peritonei who developed anti-D after receiving four units of RhD-negative RBCs during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Both patients did not receive anti-D immunoglobulin and had no previous history of anti-D detection. We retrospectively investigated and found two units of RHD*DEL1 among the RBCs transfused to these patients. Discussion: Previous reports of several cases of anti-D alloimmunization in RhD-negative recipients transfused by RHD*DEL1, an Asian-type DEL, are limited only to East Asia. We first identified 2 patients with anti-D alloimmunization after receiving the RHD*DEL1 RBCs in the Thai population. This raises concern about Rh DEL screening among D-negative Thai blood donors and whether to remove DEL units from the D-negative inventory to improve patient safety.

Double-Filtration Plasmapheresis and High-Dose Intravenous Immunoglobulin Therapy in a Case of Anti-M Alloimmunization.

Hemolytic disease is a common cause of fetal morbidity and mortality. The anti-M blood cell alloantibodies are one of the most severe causes of fetal anemia and intrauterine death. Since no standard treatment method has been established for pregnant women, the management of this pathology is through conventional methods used for treating Rh blood-type alloimmunization. For the first time, we report a unique case wherein a pregnant woman who had intrauterine fetal death in two previous pregnancies with very low titers of anti-M antibodies had negative effects during very early pregnancy, which were successfully managed in her third pregnancy with a novel protocol. We aggressively managed the blood type (anti-M antibody) and blood platelet incompatibilities (anti-HPA-4b antibody) through combination therapy twice a week (46 cycles between 12 and 34 weeks) of double filtration plasmapheresis (DFPP) and high-dose γ-globulin (20-40 g/wk). An elective cesarean section was performed at 34 weeks, and a healthy neonate was born without detection of alloantibodies in the umbilical cord blood. Our report suggests that the combination of DFPP and intravenous immunoglobulin should be considered for the treatment of anti-M alloimmunization in pregnant women.