rss_2.0Immunohematology FeedSciendo RSS Feed for Immunohematology Feed evaluation of a warm-reactive anti-M<abstract> <title style='display:none'>Abstract</title> <p>Anti-M is usually a naturally occurring antibody directed against M in the MNS blood group system. It does not require exposure to the antigen from previous transfusion or pregnancy. Anti-M is usually of the immunoglobulin M (IgM) isotype, binds best at about 4°C, binds well at room temperature, and rarely binds at 37°C. As a result of its lack of binding at 37°C, anti-M is usually clinically insignificant. There have been rare cases reported of an anti-M that reacts at 37°C. Such an exceptional anti-M may cause hemolytic transfusion reactions. We report a case of a warm-reactive anti-M and the investigational process used to identify it.</p> </abstract>ARTICLEtrue disease of the fetus and newborn mediated by anti-Di in a U.S. hospital<abstract> <title style='display:none'>Abstract</title> <p>Di<sup>a</sup> is one of the most clinically significant low-prevalence antigens in the Diego blood group system, since antibodies to Di<sup>a</sup> have, albeit rarely, been implicated in hemolytic transfusion reactions and hemolytic disease of the fetus and newborn (HDFN). Given the geographical association, most anti-Di<sup>a</sup> HDFN cases have been reported in Japan, China, and Poland. We describe a case of HDFN in a neonate born to a 36-year-old G4P2012 woman of self-identified Hispanic ethnicity and of South American descent with multiple negative antibody detection tests in a U.S. hospital. Upon delivery, a cord blood direct antiglobulin test was positive (3+ reactivity), and neonatal bilirubin levels were moderately elevated, but phototherapy and transfusion were not required. This case highlights a rare, unexpected cause of HDFN in the United States secondary to anti-Di<sup>a</sup>, given the near-universal absence of this antigen and antibody in most U.S. patient populations. The case also demonstrates the need for awareness of antibodies to antigens that are considered “low-prevalence” in most populations but that might be encountered more frequently in specific racial or ethnic groups and may require more extensive testing.</p> </abstract>ARTICLEtrue of the serologic and molecular basis of D variants with a focus on D variants in the Indian population<abstract> <title style='display:none'>Abstract</title> <p>Complexities of D within the Rh blood group system have long been recognized, initially using basic serologic testing and, more recently, using advanced and sensitive typing reagents. Discrepancies may arise when an individual carries a D antigen showing altered D antigen expression. These D variants are clinically important, since they may lead to production of anti-D in the carrier and induce alloimmunization in D− recipients, making their correct identification imperative. For clinical purposes, D variants can be classified into three groups: weak D, partial D, and DEL. The problem surrounding proper characterization of D variants exists because routine serologic tests are sometimes inadequate to detect D variants or resolve discrepant or ambiguous D typing results. Today, molecular analysis has revealed more than 300 <italic>RH</italic> alleles and is a better method for investigating D variants. Global distribution of variants differs, as observed in European, African, and East Asian populations. Discovery of the novel <italic>RHD*01W.150</italic> (weak D type 150) with a nucleotide change of c.327_487-4164dup is proof. This variant, the result of an insertion of a duplicated exon 3 between exons 2 and 4 in the same orientation, was detected in more than 50 percent of Indian D variant samples in a 2018 study. The outcome of studies worldwide has led to the recommendation to manage D variant individuals as D+ or D− according to <italic>RHD</italic> genotype. The policies and workup with respect to D variant testing in donors, recipients, and prenatal women differ among blood banks, depending on type of variants predominantly encountered. Thus, a general genotyping protocol cannot be followed globally, and an Indian-specific <italic>RHD</italic> genotyping assay (multiplex polymerase chain reaction) designed to detect D variants frequently found in the Indian population was developed to save time and resources. This assay is also helpful for detecting several partial and null alleles. Identification of D variants by serology and characterization by molecular testing need to go hand-in-hand for better and safer transfusion practices.</p> </abstract>ARTICLEtrue red blood cell antigens and phenotypes in Burkina Faso: potential issues to design local population-sourced red blood cell reagent panels<abstract> <title style='display:none'>Abstract</title> <p>To date, 43 blood group systems with 349 red blood cell (RBC) antigens have been recognized. The study of their distribution is useful for blood services to improve their supply strategies for providing blood of rare phenotypes, but also to design indigenous RBC panels for alloantibody screening and identification. In Burkina Faso, the distribution of extended blood group antigens is not known. This study aimed to investigate the extended profiles of blood group antigens and phenotypes of this population and to raise limitations and potential strategies for the design of local RBC panels. We conducted a cross-sectional study that included group O blood donors. Extended phenotyping for antigens in the Rh, Kell, Kidd, Duffy, Lewis, MNS, and P1PK systems was performed using the conventional serologic tube technique. The prevalence of each antigen and phenotype combination was determined. A total of 763 blood donors were included. The majority were positive for D, c, e, and k and negative for Fy<sup>a</sup> and Fy<sup>b</sup>. The prevalence of K, Fy<sup>a</sup>, Fy<sup>b</sup>, and C<sup>w</sup> was less than 5 percent. The most frequent Rh phenotype was Dce, and the most common probable haplotype was R<sub>0</sub>R<sub>0</sub> (69.5%). For the other blood group systems, the K−k+ (99.4%), M+N+S+s− (43.4%), and Fy(a−b−) (98.8%) phenotypes were the most frequent. Antigenic polymorphism of blood group systems by ethnicity and geography argues for the design and evaluation of population-sourced RBC panels to meet specific antibody profiles. However, some of the specificities identified in our study, such as the rarity of double-dose antigen profiles for certain antigens and the cost of antigen phenotyping tests, are major challenges to overcome.</p> </abstract>ARTICLEtrue a new carbohydrate blood group system based on a well-characterized but still mysterious antigen of great pathophysiologic interest<abstract> <title style='display:none'>Abstract</title> <p>The high-prevalence blood group antigen, Sd<sup>a</sup>, had been puzzling blood bankers and transfusionists for at least a decade when it was reported in 1967. The characteristic mix of agglutinates and free red blood cells (RBCs), caused by anti-Sd<sup>a</sup>, is seen with the RBCs from 90 percent of individuals of European descent. However, only 2–4 percent of individuals are truly Sd(a−) and may produce anti-Sd<sup>a</sup>. The antibodies, generally considered insignificant, may cause hemolytic transfusion reactions with high-expressing Sd(a+) RBCs (e.g., the unusual Cad phenotype, which can also be polyagglutinable). The Sd<sup>a</sup> glycan, GalNAcβ1-4(NeuAcα2-3)Gal-R, is produced in the gastrointestinal and urinary systems, while its origin on RBCs is more controversial. According to current theory, Sd<sup>a</sup> is likely to be passively adsorbed in low amounts, except in Cad individuals, where it has been found on erythroid proteins and at higher levels. The long-standing hypothesis that <italic>B4GALNT2</italic> encodes the Sd<sup>a</sup> synthase was confirmed in 2019, since homozygosity for a variant allele with rs7224888:C produces a non-functional enzyme associated with most cases of the Sd(a−) phenotype. Thereby, the SID blood group system was acknowledged as number 038 by the International Society of Blood Transfusion. Although the genetic background of Sd(a−) was settled, questions remain. The genetic background of the Cad phenotype has not yet been determined, and the source of the RBC-carried Sd<sup>a</sup> is unknown. Furthermore, the interest of Sd<sup>a</sup> stretches beyond transfusion medicine. Some tantalizing examples are lowered antigen levels in malignant tissue compared with normal tissue and interference with infectious agents like <italic>Escherichia coli</italic>, influenza virus, and malaria parasites.</p> </abstract>ARTICLEtrue causing severe hemolytic disease of the fetus and newborn: a rare case report<abstract> <title style='display:none'>Abstract</title> <p>Hemolytic disease of the fetus and newborn (HDFN) due to anti-D was severe and fatal before the development of RhD immune prophylaxis. Proper screening and universal administration of Rh immune globulin has decreased the incidence of HDFN to a great extent. Pregnancy, transfusion, and transplantation still increase the chances of other alloantibody formation and the potential for HDFN. Advanced methods for immunohematology investigation allow for the identification of alloantibodies causative for HDFN other than anti-D. Many antibodies have been reported to cause HDFN, but there is scant literature where isolated anti-C is responsible for HDFN. We present here a case of severe HDFN caused by anti-C leading to severe hydrops and death of the neonate despite three intrauterine transfusions and other measures.</p> </abstract>ARTICLEtrue COVID-19 vaccination and adverse events: correspondence contributors to the 2022 issues KANNO blood group system<abstract> <title style='display:none'>Abstract</title> <p>The KANNO blood group system (International Society of Blood Transfusion [ISBT] 037) includes one high-prevalence antigen, KANNO1, across ethnic groups. Sporadic KANNO1− cases among East and South Asians are theoretically estimated by the DNA database library. Anti-KANNO1 has been found most often among Japanese women with current or prior pregnancy. Thus far, there are no reported cases of hemolytic transfusion reaction or hemolytic disease of the fetus and newborn due to anti-KANNO1.</p> </abstract>ARTICLEtrue case of clinically significant anti-c in a 1-year-old pediatric patient of e and anti-e as interim terms, MAM: how the cancer-related EMP3 protein became a regulator of erythropoiesis and the key protein underlying a new blood group system<abstract> <title style='display:none'>Abstract</title> <p>The MAM blood group system (International Society of Blood Transfusion [ISBT] 041) consists of one high-prevalence antigen to date, first detected in a 31-year-old woman during her third pregnancy. Epithelial membrane protein 3 (<italic>EMP3</italic>) was recently identified as the gene coding the MAM antigen. Six unique genetic variants have been described in <italic>EMP3</italic> in 11 MAM– individuals. EMP3 is an 18-kDa glycoprotein with a large extracellular domain containing at least one <italic>N</italic>-glycosylation site. The normal function of EMP3 is still unclear, but <italic>ex vivo</italic> culture of erythropoietic progenitor cells from MAM– individuals shows an increased yield of reticulocytes, suggesting that EMP3 acts as a brake during normal erythropoiesis. EMP3 is abundant on different cell types, including many epithelial tissues and blood cells. Interestingly, EMP3 expression has been suggested as a prognostic marker for a number of cancer types, both for good and poor prognoses. EMP3 may act as a tumor suppressor or an oncogene in different cancer contexts. The protein appears to interact with other cell surface receptors and affects the downstream signaling and function of these proteins. MAM– red blood cells express low levels of CD44 and, consequently, the antigens of the Indian blood group system are only weakly expressed. Clinically, the MAM blood group antigen is important with regard to blood transfusion and pregnancy. Anti-MAM can cause severe hemolytic disease of the fetus and newborn in some pregnancies but have little to no effect in other pregnancies. Cases are typically not detected until problems occur during pregnancy, making the availability of compatible blood a challenge.</p> </abstract>ARTICLEtrue variant alleles and risk of alloimmunization in Brazilians<abstract> <title style='display:none'>Abstract</title> <p>Variant <italic>RHCE</italic> alleles are found mainly in Afro-descendant individuals, as well as in patients with sickle cell disease (SCD). The most common variants are related to the <italic>RHCE*ce</italic> allele, which can generate partial e and c antigens. Although <italic>RHCE</italic> variant alleles have been extensively studied, defining their clinical significance is a difficult task. We evaluated the risk of RhCE alloimmunization as a consequence of partial antigens in patients with a positive phenotype transfused with red blood cell (RBC) units with the corresponding antigen. A retrospective study was performed with Brazilian patients, evaluating the number of antigen-positive transfused RBC units (incompatible due to partial antigen) in 27 patients with SCD carrying <italic>RHCE</italic> variant alleles who did not develop antibodies as well as evaluating the variants present in 12 patients with partial phenotype and correlated antibody (one patient with SCD and 11 patients with other pathologies). Two patients showed variant alleles with molecular changes that had not yet been described. Variant <italic>RHCE</italic> alleles were identified in a previous study using molecular methods. <italic>RHCE*ceVS.01</italic> was the most frequent allele found among the patients without antibodies. Six patients with partial c antigen had a mean of 3.8 c+ RBC units transfused, and 10 patients with partial e antigen were exposed for a mean of 7.2 e+ RBC units. Among the variant alleles found in alloimmunized patients, the most frequent was <italic>RHCE*ceAR,</italic> which was found in five patients; the antibodies developed were anti-hr<sup>S</sup> and/or anti-c. Our results showed that <italic>RHCE*ceVS.01</italic> is indeed the most frequent variant allele in our cohort of patients with SCD, but the partial antigens that were identified have low risk of alloimmunization. <italic>RHCE*ceAR</italic> is the most impactful variant in the Brazilian population with high risk of alloimmunization and clinically significant anti-hr<sup>S</sup> formation.</p> </abstract>ARTICLEtrue page warm autoimmune hemolytic anemia proceeding the administration of the Pfizer mRNA COVID-19 vaccine treatment of red blood cells: use of ficin and papain<abstract> <title style='display:none'>Abstract</title> <p>Proteolytic enzymes are used to treat red blood cells (RBCs) to aid in complex antibody identification. Although there are many enzymes that can be used, for the purpose of this method review, enzyme-treated RBCs refers only to RBCs treated with ficin or papain. Ficin and papain can increase the sensitivity of antibody detection by modifying the RBC membrane. Enzyme treatment and test methods can be performed using one-stage or two-stage procedures. Enzyme treatment is especially useful for the differentiation of multiple antibodies, enhancement of detection of weak antibodies, and adsorption methods. In all cases, quality control is required to ensure adequate treatment of RBCs before additional testing. Ficin and papain are useful tools for both immunohematology reference laboratories and transfusion services.</p> </abstract>ARTICLEtrue