Major reduction in occurrence of anti-c and anti-E in pregnancy after more than 10 years of preventive matched transfusion with most benefit for c-matching.

Extension with cE-matching of the transfusion policy for women under 45 years to prevent alloimmunization and hemolytic disease of the foetus and newborn (HDFN) was evaluated. After implementation of cEK-matching, anti-c occurrence decreased from 46.8 to 30.4 per 100 000 pregnancies (RR 0.65, 95% CI 0.54-0.79), while anti-E occurrence decreased from 122.1 to 89.9 per 100 000 pregnancies (RR 0.74, 95% CI 0.66-0.84). The c-negative women showed a higher anti-E occurrence before cEK-matching and a more pronounced decline with the new policy. This indicates that cEK-matched transfusion effectively reduces alloimmunization, and that a cK-matched approach could prevent most transfusion-related alloimmunization and HDFN.

The American Rare Donor Program: 25 years supporting rare blood needs.

Rare donor programs are critically important for those patients with rare phenotypes who have produced the associated alloantibodies that necessitate the provision of rare blood components. We describe the American Rare Donor Program (ARDP) and its establishment, members, and policies. The specific phenotypes meeting the ARDP criteria for inclusion are described. Data on the number of rare donors registered by year, and the number of requests for rare blood components received and fulfilled over the 25 years of the program (1998-2023) are provided, along with a description of some notable cases and discussion of how the program supports patients with sickle cell disease.

International Society of Blood Transfusion Working Party on Red Cell Immunogenetics and Blood Group Terminology Report of Basel and three virtual business meetings: Update on blood group systems.

BACKGROUND AND OBJECTIVES: Under the ISBT, the Working Party (WP) for Red Cell Immunogenetics and Blood Group Terminology is charged with ratifying blood group systems, antigens and alleles. This report presents the outcomes from four WP business meetings, one located in Basel in 2019 and three held as virtual meetings during the COVID-19 pandemic in 2020 and 2021. MATERIALS AND METHODS: As in previous meetings, matters pertaining to blood group antigen nomenclature were discussed. New blood group systems and antigens were approved and named according to the serologic, genetic, biochemical and cell biological evidence presented. RESULTS: Seven new blood group systems, KANNO (defined numerically as ISBT 037), SID (038), CTL2 (039), PEL (040), MAM (041), EMM (042) and ABCC1 (043) were ratified. Two (039 and 043) were de novo discoveries, and the remainder comprised reported antigens where the causal genes were previously unknown. A further 15 blood group antigens were added to the existing blood group systems: MNS (002), RH (004), LU (005), DI (010), SC (013), GE (020), KN (022), JMH (026) and RHAG (030). CONCLUSION: The ISBT now recognizes 378 antigens, of which 345 are clustered within 43 blood group systems while 33 still have an unknown genetic basis. The ongoing discovery of new blood group systems and antigens underscores the diverse and complex biology of the red cell membrane. The WP continues to update the blood group antigen tables and the allele nomenclature tables. These can be found on the ISBT website (http://www.isbtweb.org/working-parties/red-cell-immunogenetics-and-blood-group-terminology/).

Phenotype frequencies of Rh (C, c, E, e), M, Mia and Kidd blood group systems among ethnic Thai blood donors from the north-east of Thailand.

We here report the first study of antigen and phenotype frequencies of Rh (C, c, E, e), M, Mia and Kidd antigens in north-east Thai blood donors. Blood transfusion services aim to ensure availability of adequate and safe blood to minimize the development of transfusion reactions. For pre-transfusion testing, the most important blood group systems are ABO and RhD. The transfusion of ABO-compatible otherwise unknown phenotype blood may result in alloimmunization, especially in multi-transfused patients. Extended red blood cell (RBC) phenotyping and selection of blood negative for specific antigens reduce post-transfusion complications and allow for effective blood transfusion regimens to be achieved. A total of 13,567 regular repeated, voluntary Thai blood donors were included for red-cell antigen typing of Rh (D, C, E, c, e). Samples from 12,768, 9,389 and 13,059 donors were typed for Kidd, M and Mia antigens, respectively. Amongst Rh antigens, e was the most common (96.80%) followed by C (95.50%), c (34.40%) and E (32.20%) with CCDee (60.00%) being the most common phenotype. For Kidd phenotypes, Jk(a+b+) was the most common (46.73%) and Jk(a-b-) was rare (0.07%). For the M and Mia antigen, M(+) was most frequently found (94.96%) and Mia (+) was found in 17.97% of individuals. Knowledge of red-cell antigen phenotype frequencies in a population is helpful for creating a phenotype database of blood donors which can provide antigen-negative compatible blood to patients with multiple alloantibodies. Moreover, provision of antigen-matched blood can prevent alloimmunization in multi-transfused patients.

Retrospective analysis of HDFN due to ABO incompatibility in a single institution over 6 years.

OBJECTIVES: To study the rate of ABO haemolytic anaemia of fetus and newborn (HDFN) in one institution over 6 years. BACKGROUND: ABO major incompatibility between mothers and their newborns occurs in about 10% of births. So, mothers with an O blood group may form IgG-class antibodies against A and B antigens, which could pass across the placenta and lead to a variable degree of HDFN in the newborn. METHODS: At our institution, we have reviewed data regarding ABO-based HDFN in the last 6 years. RESULTS: We found that, in 28 089 deliveries, an ABO major incompatibility between mothers and newborns occurs in 11% of cases, with 72% of O/A and 28% of O/B incompatibility. In turn, 23% of these newborns had an eluate-confirmed positive direct antiglobulin test [DAT; 74% (511) were due to anti-A and 26% (179) to anti-B], with 1·0% requiring invasive treatments (exchange transfusion or intravenous immunoglobulin). Overall, 2·5% of the total newborns had a positive DAT for an anti-A or anti-B antibody, and 0·11% required invasive treatment in addition to phototherapy for their HDFN. CONCLUSIONS: Serological ABO HDFN is a relatively frequent event when an O-A/O-B incompatibility between mothers and their newborn occurs and, in most cases, translates into a self-limiting disease, with a small number of newborns requiring invasive treatments. The DAT test, although not predictive of disease severity, appears to be a useful tool to monitor babies born from O-A/O-B-incompatible pregnancies and to identify those who may require treatment.

Genetic background of the rare Yus and Gerbich blood group phenotypes: homologous regions of the GYPC gene contribute to deletion alleles.

The GYPC gene encodes the glycophorins C and D. The two moieties express 12 known antigens of the Gerbich blood group system and functionally stabilize red blood cell membranes through their intracellular interaction with protein 4.1 and p55. Three GYPC exon deletions are responsible for the lack of the high-frequency antigens Ge2 (Yus type, exon 2 deletion), Ge2 and Ge3 (Gerbich type, exon 3 deletion), and Ge2 to 4 (Leach type, exons 3 and 4 deletion), but lack exact molecular description. A total of 29 rare blood samples with Yus (GE:-2,3,4) and Gerbich (GE:-2,-3,4) phenotypes, including individuals of Middle-Eastern, North-African or Balkan ancestry were examined genetically. All phenotypes could be explained by 4 different Yus alleles, characterized by deletions of exon 2 and adjacent introns, and 3 different Gerbich alleles, with deletions of exon 3 and adjacent introns. A 3600 base pair GYPC region, encompassing exon 2 and flanking region, shares a high degree of sequence homology with a region flanking exon 3, probably representing an evolutionary duplication event. Defining the expression of Gerbich variants presently relies on rare serological reagents. Our approach substitutes the serological characterization with a precise genotype approach to identify the rare Yus and Gerbich alleles.

Antigen specificity determines anti-red blood cell IgG-Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn.

Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG alloantibodies. HDFN is most often caused by anti-D but may also occur due to anti-K, -c- or -E. We recently found N-linked glycosylation of anti-D to be skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc receptor IIIa and IIIb, which correlated with HDFN disease severity. Here, we analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a prospective screening cohort and investigated the type of Fc-tail glycosylation of these antibodies in relation to the trigger of immunisation and pregnancy outcome. Anti-c, -E and -K show - independent of the event that had led to immunisation - a different kind of Fc-glycosylation compared to that of the total IgG fraction, but with less pronounced differences compared to anti-D. High Fc-galactosylation and sialylation of anti-c correlated with HDFN disease severity, while low anti-K Fc-fucosylation correlated with severe fetal anaemia. IgG-Fc glycosylation of anti-RBC antibodies is shaped depending on the antigen. These features influence their clinical potency and may therefore be used to predict severity and identify those needing treatment.

The dog erythrocyte antigen 1 blood group in nondomesticated canids and compatibility testing between domestic dog and nondomesticated canid blood.

BACKGROUND: The dog erythrocyte antigen (DEA) 1 blood group is considered as the most immunogenic and clinically important in dogs. Little is known in nondomesticated canids. OBJECTIVES: To type DEA 1 in nondomesticated captive canids and to evaluate potential interspecific blood transfusions between domestic and nondomestic canids. ANIMALS: One hundred forty captive nondomesticated canids belonging to 13 species from 19 French zoos, and 63 domestic dogs. METHODS: Prospective study. Blood samples were typed for DEA 1 using immunochromatographic and flow cytometric techniques. A neutral gel column test was used for crossmatching. RESULTS: Of 140 nondomesticated canids, 72.9% were DEA 1+ and 27.1% were DEA 1- using immunochromatographic technique and 74.3% were DEA 1+ and 25.7% were DEA 1- by flow cytometric technique. Crossmatch (XM) between 140 nondomesticated canid red blood cells (RBCs) and plasma from a previously DEA 1+ sensitized DEA 1- dog revealed 112 incompatibilities (80%). Crossmatches between 130 nondomesticated canid serum and 1 or up to 8 donor dogs' RBCs revealed 99 of 130 (76%) compatibilities. Crossmatches between 115 nondomesticated canid RBCs and donor dogs' serum revealed 59 of 115 (51%) compatibilities. CONCLUSIONS AND CLINICAL IMPORTANCE: Dog erythrocyte antigen 1 blood type is present in nondomesticated canids with variable prevalence depending on species. The majority of tested nondomesticated canids appear to have no naturally occurring alloantibodies against domestic dogs' RBCs. Therefore xenotransfusion of blood from domestic dogs can be considered when species specific blood is not available. Cross matching is essential before xenotransfusion.

Red blood cell antibodies in thalassemia patients in northern India: risk factors and literature review.

Study of the factors responsible for red cell alloimmunization can help in adopting appropriate strategy to minimize alloimmunization. However data for thalassemia patients from our region is limited. Therefore, a study was conducted to find out the frequency and the factors associated with red cell allo and autoimmunization in thalassemia patients at our center so as to enable us to take appropriate action to reduce alloimmunization. Clinical, demographic, allo and autoantibody and transfusion records of 280 thalassemia patients at our hospital were studied. Patients with and without alloantibodies were compared to find significant differences for age, gender, race, age at start of regular transfusions and splenectomy. Red cell antigen frequencies in thalassemia patients and published antigen frequencies in blood donors from the same center were compared to look antigen differences as a risk factor for alloimmunization. Twenty four thalassemia patients (8.6 %) developed 28 clinically significant alloantibodies. 18 (65 %) of the alloantibodies were of Rh system. The three most common antibodies detected was anti E (11, 39.3 %) followed by anti K (6, 21.4 %) and anti c (10.8 %). Five (1.8 %) of the 280 patients developed autoantibodies. Patient age was found to be significantly higher in alloimmunized patients than in non alloimmunized patients. Red cell antigen frequencies between blood donor and recipient populations were found to be homogenous for most of the relevant RBC antigens. The frequency of red cell alloimmunization in thalassemia patients from our center is moderate. In this setting of red cell phenotype concordant donor-recipient population requirement of extended phenotype matched transfusions may not be cost effective.

Phenotype frequencies of blood group systems (Rh, Kell, Kidd, Duffy, MNS, P, Lewis, and Lutheran) in blood donors of south Gujarat, India.

BACKGROUND: This is the first study on phenotype frequencies of various blood group systems in blood donors of south Gujarat, India using conventional tube technique. MATERIAL AND METHODS: A total of 115 "O" blood group donors from three different blood banks of south Gujarat were typed for D, C, c, E, e, K, Jk(a), Le(a), Le(b), P1, M, and N antigens using monoclonal antisera and k, Kp(a), Kp(b), Fy(a),Fy(b), Jk(b), S,s, Lu(a), and Lu(b) antigens were typed using polyclonal antisera employing Indirect Antiglobulin Test. Antigens and phenotype frequencies were expressed as percentages. RESULTS: From the 115 blood donor samples used for extended antigen typing in the Rh system, e antigen was found in 100% donors, followed by D [84.35%], C [81.74%], c [56.32%], and E [21.74%] with DCe/DCe (R1 R1, 40.87%) as the most common phenotype. k was found to be positive in 100% of donors and no K+k- phenotype was found in Kell system. For Kidd and Duffy blood group system, Jk(a+b+) and Fy(a-b-) were the most common phenotypes with frequency of 52.17% and 48.69%, respectively. In the MNS system, 39.13% donors were typed as M+N+, 37.39% as M+N-, and 23.48% as M-N+. S+s+ was found in 24.35% of donors, S+s- in 8.69%, and S-s+ as the commonest amongst donors with 66.96%. No Lu(a+b+) or Lu(a+b-) phenotypes were detected in 115 donors typed for Lutheran antigens. A rare Lu(a-b-) phenotype was found in 2.61% donors. CONCLUSION: Data base for antigen frequency of various blood group systems in local donors help provide antigen negative compatible blood units to patients with multiple antibodies in order to formulate in-house red cells for antibody detection and identification and for preparing donor registry for rare blood groups.