<abstract>
<title style='display:none'>Abstract</title>
Individuals with the rare para-Bombay phenotype have inherited defects in producing H associated with <italic>FUT1</italic> and/or <italic>FUT2</italic> genes. We report a case of blood group discrepancy in a para-Bombay patient from a tertiary care hospital of eastern India. A 31-year-old woman with rheumatic heart disease presented with fatigue and breathlessness and was then scheduled for valvuloplasty, for which a blood transfusion request was sent to the blood center. During pre-transfusion testing, red blood cell (RBC) testing showed group O, and serum testing showed strong reactivity with group B RBCs, weak reactivity with group O RBCs, and very weak reactivity with group A RBCs. Saliva inhibition testing and enzyme treatment of RBCs concluded the patient to be of “Ah para-Bombay” phenotype. The patient’s Lewis phenotype was Le(a–b+). This patient’s serum also had cold-reacting anti-IH along with anti-B. This case report highlights the importance of performing an advanced immunohematologic workup, including adsorption, elution, enzyme treatment, and saliva inhibition testing for identification of weak A or B subgroups as well as the rare para-Bombay blood group, when routine ABO typing, using forward and reverse grouping, is inconclusive. Accurate identification of blood group helps in preventing transfusion-related adverse events and encouraging safe transfusion practice.
</abstract>

Blood group discrepancy in Ah para-Bombay phenotype: a rare blood group variant and its clinical significance

<abstract>
<title style='display:none'>Abstract</title>
Red blood cell alloimmunization to antigens other than D, such as C, c, E, e, and antigens in the Kell, MNS, and Duffy blood group systems, has emerged as an important cause of hemolytic disease of the fetus and newborn (HDFN). Antibody screening for these antibodies is not routinely practiced for all antenatal patients in developing countries, mainly because of financial constraints. Here we report a rare case of HDFN due to dual antibodies to Rh and Kidd blood group system antigens: anti-E and anti-Jka. This case report highlights the importance of routine and regular antenatal screening of all pregnant women for proper monitoring and follow-up.
</abstract>

Severe hemolytic disease of the fetus and newborn due to anti-E and anti-Jka

<abstract>
<title style='display:none'>Abstract</title>
The high number of D variants can lead to the unnecessary use of Rh immune globulin, overuse of D− RBC units, and anti-D allommunization. D variant prevalence varies among ethnic groups, and knowledge of the main variants present in a specific population, their behavior in serologic tests, and their impact on clinical practice is crucial to define the best serologic tests for routine use. The present study aimed to explore the serologic profile of D variants and to determine which variants are most associated with false-negative D typing results and alloimmunization. Donor samples were selected in two study periods. During the first period, D typing was performed on a semi-automated instrument in microplates, and weak D tests were conducted in tube or gel tests. In the second period, D typing was carried out using an automated instrument with microplates, and weak D tests were performed in solid phase. Samples from patients typed as D+ with anti-D were also selected. All samples were characterized by molecular testing. A total of 37 <italic>RHD</italic> variants were identified. Discrepancies and atypical reactivity without anti-D formation were observed in 83.4 percent of the samples, discrepant D typing results between donations were seen in 12.3 percent, and D+ patients with anti-D comprised 4.3 percent. DAR1.2 was the most prevalent variant. Weak D type 38 was responsible for 75 percent of discrepant samples, followed by weak D type 11, predominantly detected by solid phase. Among the D variants related to alloimmunization, DIVa was the most prevalent, which was not recognized by serologic testing; the same was true for DIIIc. The results highlight the importance of selecting tests for donor screening capable of detecting weak D types 38 and 11, especially in populations where these variants are more prevalent. In pre-transfusion testing, it is crucial that D typing reagents demonstrate weak reactivity with DAR variants; having a serologic strategy to recognize DIVa and DIIIc is also valuable.
</abstract>

Serologic profiling of D variants in donor routine: unveiling the impact on false-negative results and alloimmunization

<abstract>
<title style='display:none'>Abstract</title>
This update on the P1PK blood group system (Hellberg Å, Westman JS, Thuresson B, Olsson ML. P1PK: the blood group system that changed its name and expanded. Immunohematology 2013;29:25–33) provides recent findings concerning the P1PK blood group system that have both challenged and confirmed old theories. The glycosphingolipids can no longer be considered the sole carriers of the antigens in this system because the P1 antigen has been detected on human red blood cell glycoproteins. New indications suggest that P1Pk synthase activity truly depends on the DXD motif, and the genetic background and molecular mechanism behind the common P1 and P2 phenotypes were found to depend on transcriptional regulation. Transcription factors bind the <italic>P<xref ref-type="bibr" rid="j_immunohematology-2020-048_ref_001">1</xref>
</italic> allele selectively to a motif around rs5751348 in a regulatory region of <italic>A4GALT</italic>, which enhances transcription of the gene. Nonetheless, unexplained differences in antigen expression between individuals remain.
</abstract>

The P1PK blood group system: revisited and resolved

<abstract>
<title style='display:none'>Abstract</title>
Solid-phase red cell adherence (SPRCA) is a sensitive platform for antibody detection, but nonspecific reactions may occur. One pattern of apparent nonspecific reactivity is a panagglutinin with a negative direct antiglobulin test (DAT). The purpose of this study was to define the clinical characteristics of patients with these nonspecific reactions and their associated serologic findings. Twenty patients with panreactive SPRCA testing results were identified between November 2022 and May 2023. In addition to panagglutinins, these patients had (1) a negative polyethylene glycol (PEG) antibody detection test, (2) a negative PEG autocontrol, and (3) a negative DAT. The strength of SPRCA panreactivity and the results of eluate testing (by tube and SPRCA) were studied. Clinical characteristics of patients included age, sex, and primary diagnosis. Each patient was also assessed for evidence of hemolysis. Fourteen female and six male patients were evaluated (average age 44 years). Primary diagnoses included pregnancy (<italic>n</italic> = 10), acute bleeding (<italic>n</italic> = 4), orthopedic (<italic>n</italic> = 3), and other (<italic>n</italic> = 3). There was no clinical or laboratory evidence of hemolysis. The predominant strength of SPRCA panreactivity was evenly distributed across reaction grades (1+ to 3+). Fifty-five percent of the eluates tested in PEG showed panreactivity, consistent with warm-reactive autoantibodies, while 85 percent of eluates tested by SPRCA were panreactive. Six discrepant cases, in which PEG eluate testing was negative and solid-phase eluate testing showed panreactivity, were associated with weak solid-phase plasma panreactivity (1+). In addition, the reactivity strengths of the eluates tested by SPRCA were invariably more strongly reactive than those eluates tested in PEG. Panagglutination is a distinct SPRCA-only plasma reactivity pattern. Despite a negative PEG tube and DAT, most panagglutinins are warm-reactive autoantibodies. Fortunately, these “interfering” panagglutinins do not appear to be clinically significant and are easily managed by an alternative testing method such as PEG.
</abstract>

Evaluation of solid-phase panreactivity with negative direct antiglobulin testing

<abstract>
<title style='display:none'>Abstract</title>
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.
</abstract>

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

<abstract>
<title style='display:none'>Abstract</title>
Anti-f is produced by exposure to the compound antigen ce (f) on red blood cells (RBCs), expressed when both c and e are present on the same protein (<italic>cis</italic> position). Although anti-f was discovered in 1953, there are few cases reported worldwide because the presence of anti-f is often masked by anti-c or anti-e and is not generally found as a single antibody. In the present case, anti-f was identified by using three-cell screening and 11-cell identification panels. The identification of anti-f was further supported by additional testing, including (1) Rh antigen typing; (2) antibody identification panels (enzyme-treated panel [ficin] and an in-house–constructed Rh panel); (3) look-back and phenotyping of donor RBC units, which were responsible for alloimmunization; and (4) molecular testing of the patient’s RBCs.
</abstract>

A patient with anti-f in India identified by extensive immunohematologic workup

<abstract>
<title style='display:none'>Abstract</title>
Autoimmune hemolytic anemia (AIHA) is a common term for several disorders that differ from one another in terms of etiology, pathogenesis, clinical features, and treatment. Management of patients with AIHA has become increasingly evidence-based in recent years. While this development has resulted in therapeutic improvements, it also carries increased requirements for optimal diagnosis using more advanced laboratory tests. Unfortunately, limited data are available from developing countries regarding the testing and transfusion management of patients with AIHA. The main objective of this survey was to explore the current immunohematologic testing practices for the diagnosis of AIHA in India. This online survey consisted of 30 questions, covering the place of work, the number of AIHA cases encountered in the 3 preceding years, testing method(s), transfusion management, and so forth. Individuals representing 89 laboratories completed the survey; only 78 of which responded that AIHA testing was performed in their facility’s laboratory. The majority of respondents agreed that the most commonly affected age-group comprised individuals of older than 20 years, with a female preponderance. Regarding transfusion management, respondents indicated that transfusion with “best-match” red blood cell units remains the most common practice. Column-agglutination technology is used by 92 percent of respondents as the primary testing method. Although a monospecific direct antiglobulin test is available at 73 percent of the sites, most of them have limited access to other resources that could diagnose cold or mixed AIHA. Merely 49 percent of responding laboratories have the resources to perform adsorption studies for the detection of alloantibodies. Furthermore, three-cell antibody screening reagents are unavailable at 32 percent of laboratories. In 72 percent of centers, clinical hematologists would prefer to consult a transfusion medicine specialist before administering treatment to AIHA patients. There is unanimous agreement regarding the need for a national registry. The survey data indicate wide variability in testing practices for patients with AIHA in India. Future studies are needed to focus on the feasibility and cost-effectiveness of different testing strategies for developing countries.
</abstract>

A national survey of current immunohematologic testing practices for the diagnosis of autoimmune hemolytic anemia in India

<abstract>
<title style='display:none'>Abstract</title>
This review aims to provide a better understanding of when and why red blood cell (RBC) genotyping is applicable in transfusion medicine. Articles published within the last 8 years in peer-reviewed journals were reviewed in a systematic manner. RBC genotyping has many applications in transfusion medicine including predicting a patient’s antigen profile when serologic methods cannot be used, such as in a recently transfused patient, in the presence of autoantibody, or when serologic reagents are not available. RBC genotyping is used in prenatal care to determine zygosity and guide the administration of Rh immune globulin in pregnant women to prevent hemolytic disease of the fetus and newborn. In donor testing, RBC genotyping is used for resolving ABO/D discrepancies for better donor retention or for identifying donors negative for high-prevalence antigens to increase blood availability and compatibility for patients requiring rare blood. RBC genotyping is helpful to immunohematology reference laboratory staff performing complex antibody workups and is recommended for determining the antigen profiles of patients and prospective donors for accurate matching for C, E, and K in multiply transfused patients. Such testing is also used to determine patients or donors with variant alleles in the Rh blood group system. Information from this testing aides in complex antibody identification as well as sourcing rare allele-matched RBC units. While RBC genotyping is useful in transfusion medicine, there are limitations to its implementation in transfusion services, including test availability, turn-around time, and cost.
</abstract>

When and why is red blood cell genotyping applicable in transfusion medicine: a systematic review of the literature

<abstract>
<title style='display:none'>Abstract</title>
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.
</abstract>

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

<abstract><title style='display:none'>Abstract</title>The antigens of the ABO system were the first to be recognized as blood groups and actually the first human genetic markers known. Their presence and the realization of naturally occurring antibodies to those antigens lacking from the cells made sense of the erratic failure of blood transfusion hitherto and opened up the possibility of a safe treatment practice in life-threatening blood loss. Although initially apparently simple, the ABO system has come to grow in complexity over the years. The mass of knowledge relating to carbohydrate chemistry, enzymology, molecular genetics, and structural and evolutionary biology is now enormous thanks to more than a century of research using ABO as a principal model. This has provided us with data to form a solid platform of evidence-based transfusion and transplantation medicine used every day in laboratories and clinics around the globe. This review aims to summarize key findings and recent progress made toward further understanding of this surprisingly polymorphic system. <italic><bold>Immunohematology</bold></italic><bold>2009;25:48–59.</bold></abstract>

The ABO blood group system revisited: a review and update

<abstract><title style='display:none'>Abstract</title>Although recognized as a serious complication of hemotherapy, few data are available on the incidence of transfusion-associated circulatory overload (TACO). Detailed demographic and clinical information was obtained from records of 382 Medicare patients undergoing total hip or knee replacements (and receiving transfusions) from January 1992 to December 1993 at five Massachusetts hospitals. Seventy-eight percent of the patients were women with a mean age of 77 years. Thirty-two percent had co-morbidities including myocardial or coronary disease. Transfusion-related complications and comorbidities were identified and reviewed by transfusion experts. Patients were excluded from consideration if non-transfusion factors such as myocardial disease could have contributed to the development of acute pulmonary edema. Four (3 females, 1 male) patients (1.05%) developed TACO postoperatively. Mean age of these patients was 84 years (range, 75–101) versus 77 years for non-TACO. The mean intraoperative estimated blood loss was 375 mL. Each patient received only 1–2 units of red blood cells prior to onset of TACO, and in two cases only autologous blood was used. The mean positive fluid balance was 2,480 mL. The mean pretransfusion hematocrit prior to circulatory overload (CO) was 26.0 percent. symptoms were reversed with diuretics. Length of stay was significantly prolonged by these incidents. TACO is a frequent and serious event in an orthopedic surgical setting. It is associated with advanced age, increased health care costs, and may occur in the setting of modest transfusion volumes. The utilization of conservative transfusion criteria and fluid management in the perioperative setting may decrease the incidence of this complication in this population. <bold><italic>Immunohematology</italic></bold> 1996;12:87–89.</abstract>

Massachusetts Peer Review Organization, Inc.

Transfusion-associated circulatory overload in orthopedic surgery patients: a multi-institutional study

Review: ABO blood group system—ABH oligosaccharide antigens, anti-A and anti-B, A and B glycosyltransferases, and <italic>ABO</italic> genes

<abstract><title style='display:none'>Abstract</title>Despite yielding a definitive diagnosis in fewer than 20 percent of anaphylactic transfusion reactions, investigation for IgA deficiency and the presence of presumably pathogenic IgG anti-IgA is useful in patient management. Individuals with demonstrated anti-IgA are thereafter committed to receiving IgA-depleted cellular products or IgA-deficient plasma and derivatives to prevent recurrent severe reactions. Unfortunately, in populations of IgA-deficient individuals screened for anti-IgA, the predictive value of the test in the absence of a prior reaction is quite low. Anti-IgA testing is complex and limited to a few reference laboratories, many of which still employ a labor-intensive hemagglutination assay developed in the late 1960s. Timely decisions regarding further transfusion management of patients experiencing anaphylaxis often rely upon more rapidly obtained assays of the IgA concentration as an indicator of the likelihood of subsequent demonstration of anti-IgA. The scarcity of IgA-deficient banked plasma products and dedicated platelet-pheresis donors has led to the development of American Rare Donor Program policies designed to appropriately allocate these precious resources. The test methods used to establish the diagnosis of IgA deficiency and identify the approximately one-third of these individuals with anti-IgA are discussed, along with the incidence of abnormal tests in various populations. Also presented are testing recommendations for the identification of an IgA-mediated mechanism for transfusion-associated anaphylaxis and qualification of patients to receive rare IgA-deficient plasmacontaining products. <bold><italic>Immunohematology</italic> 2005;21 :226–233.</bold></abstract>

Review: IgA anaphylactic transfusion reactions.Part I. Laboratory diagnosis, incidence, and supply of IgA-deficient products

<abstract><title style='display:none'>Abstract</title>Neutrophils are the most abundant white blood cell in blood and play a critical role in preventing infections as part of the innate immune system. Reduction in neutrophils below an absolute count of 500 cells/μL is termed severe neutropenia or agranulocytosis. Drug-induced immune neutropenia (DIIN) occurs when drug-dependent antibodies form against neutrophil membrane glycoproteins and cause neutrophil destruction. Affected patients have fever, chills, and infections; severe infections left untreated can result in death. Treatment with granulocyte colony-stimulating factor can hasten neutrophil recovery. Cumulative data show that severe neutropenia or agranulocytosis associated with exposure to nonchemotherapy drugs ranges from approximately 1.6 to 15.4 cases per million population per year. Drugs most often associated with neutropenia or agranulocytosis include dipyrone, diclofenac, ticlopidine, calcium dobesilate, spironolactone, antithyroid drugs (e.g., propylthiouracil), carbamazepine, sulfamethoxazole-trimethoprim, β-lactam antibiotics, clozapine, levamisole, and vancomycin. Assays used for detection of neutrophil drug-dependent antibodies (DDAbs) include flow cytometry, monoclonal antibody immobilization of granulocyte antigens, enzyme-linked immunosorbent assay, immunoblotting, granulocyte agglutination, and granulocytotoxicity. However, testing for neutrophil DDAbs is rarely performed owing to its complexity and lack of availability. Mechanisms proposed for DIIN have not been rigorously studied, but those that have been studied include drug- or hapten-induced antibody formation and autoantibody production against drug metabolite or protein adducts covalently attached to neutrophil membrane proteins. This review will address acute, severe neutropenia caused by neutrophil-reactive antibodies induced by nonchemotherapy drugs—DIIN. <italic><bold>Immunohematology</bold></italic><bold>2014;30:95–101.</bold></abstract>

Drug-induced immune neutropenia/ agranulocytosis

Review: the molecular basis of the Rh blood group phenotypes

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