Risk Of Alloimmunization Research Articles

Frequency and characterization of RHD and RHCE variants in the Noir Marron population from French Guiana.

The RH system is one of the most polymorphic blood group systems due to the proximity and opposite orientation of RHD and RHCE genes. Numerous alleles are described and can affect Rh protein expression. This complexity is especially evident in populations of African origin. We performed RHD and RHCE genotyping of the Noir Marron population in French Guiana. This population belongs to the Maroon community who are direct descendants of African slaves, who escaped from Dutch plantations, in the current day Suriname, during the 17th century. They represent an original ethnic group with highly blended culture. A total of 89 DNA samples were collected from four different ethnic groups of the Noir Marron population of French Guiana. RHD and RHCE genotyping was performed using DNA microarray and/or sequencing. Significant allelic diversity was shown, with 45% of individuals presenting an RHD gene variant (most common: RHD*DAU, RHD*DIVa, and RHD*DIIIa allele) and 9.4% with a partial D phenotype. Likewise, 85% presenting an RHCE gene variant and 9% a partial RH2 antigen. One original allele was identified in two D+ Noir Marron individuals: a hybrid RHD*DIIIa-CE(9)-D allele, encoding probably a partial D antigen and associated with an RHCE*ce(48C,733G,1006T) allele. The African diversity of RHD and RHCE genes is found in this population with preserved genetic but mixed cultural backgrounds. These data allow us to describe the characteristics of the RH system antigen and highlights a significant number of partial antigens with a risk of alloimmunization.

Somatic mutations show no clear association with red blood cell or human leukocyte antigen alloimmunization in de novo or therapy-related myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a marrow failure disease. As patients often require chronic transfusion, many develop red blood cell (RBC) alloimmunization or immune-mediated platelet refractoriness. MDS represents a spectrum of diseases with specific categorizations and genetic abnormalities, and we set out to determine if these characteristics predispose patients to antibody formation. A natural language search identified MDS patients with pre-transfusion testing from 2015 to 2020. Marrow reports, cytogenetic results, and next-generation sequencing panels were gathered. Transfusion history and testing were collected from the laboratory information system. The group consisted of 226 biopsy-proven MDS patients. The prevalence of RBC alloimmunization was 11.1% (25 of 226). Half (23 of 46) of all RBC alloantibodies were against Rh (C, c, E, e) and Kell (K) antigens. There was a relative enrichment for JAK2 positivity among the RBC alloimmunized group. A total of 7.1% (16 of 226) of patients had immune-mediated platelet refractoriness and had increased transfusion requirements (p ≤ 0.01). No disease type or genetic abnormality was significantly associated with alloimmunization or immune-mediated platelet refractoriness. While JAK2 specific mutations were enriched among RBC alloimmunized patients, this association failed to reach statistical significance in our single-center cohort. Further study using larger patient cohorts is warranted. Overall, this cohort of MDS patients had very similar RBC alloimmunization prevalence and anti-RBC antibody specificities as other recent literature. Our data reinforce the finding that MDS patients are at greater risk for alloimmunization and support the use of extended phenotype matching for these at-risk patients.

The Women Have Spoken: A Patient-Centered National Survey on Use of Emergent O+ Transfusion

INTRODUCTION: Hemorrhage is the leading cause of preventable death after trauma. Alloimmunization risk and later serious fetal harm from emergency transfusion of O+ blood is estimated at 1% to 6%. Limited availability of O- blood may lead to female lives lost over concern for their future children. We sought to characterize how women in the at-risk population feel about emergency blood use and potential future fetal harm. METHODS: A national survey was performed using Facebook advertisements and Qualtrics XM software in 3 waves from January 2021 to January 2022. Advertisements directed users to the survey site with 7 demographic questions and 4 questions on accepting transfusion with differing probabilities for future fetal harm (none/any/1:100/1:10,000). Transfusion questions were scored on a 3-point Likert scale (likely/neutral/unlikely). Completion was required for analysis. Childbearing age was defined as 15 to 49 years old. RESULTS: The advertisements were viewed 16,600,430 times by 2,169,805 people with 15,396 advertisement clicks and 2,873 surveys initiated. Most (79%; 2,256 of 2,873) were fully completed. The majority (90%; 2,049 of 2,256) of respondents were female. Of females, 80% (1,645 of 2,049) were childbearing age. Most women responded likely or neutral to accept lifesaving transfusion with the following: no risk fetal harm (99%); any risk (83%); 1:100 risk (85%); and 1:10,000 risk (92%). A minority answered unlikely to the same questions: no risk fetal harm (1%); any risk (17%); 1:100 risk (15%); and 1:10,000 risk (9%). The was no difference in females likely to accept lifesaving transfusion with any potential for future fetal harm when stratified by childbearing age (p = 0.24). CONCLUSION: This national survey suggests the majority of women would accept lifesaving transfusion even with potential risk of future fetal harm.

Incidence of Red Cell Antibody Formation Following Massive Transfusion Protocol: Experience of a Single Institution.

Injured patients in hemorrhagic shock have a survival benefit with massive transfusion protocol (MTP). While there are many published studies on the transfusion management of massively bleeding patients, the risk of alloimmunization in patients that have received products during an MTP activation is relatively unknown. Therefore, we sought to determine the frequency of new antibody formation in MTP patients that received blood products from an uncrossmatched megapack. We conducted a retrospective data review of patients who underwent an MTP activation for trauma resuscitation between May 2014 and July 2020. Data were collected from patients who met the following criteria: MTP was activated, the patients received at least one unit of packed red blood cells, one unit of fresh frozen plasma, one unit of platelets, and had a repeat type and screen within 6 weeks of transfusion. These inclusion criteria resulted in 28 patients over the 6-year timeframe. Overall, the risk of alloimmunization secondary to MTP is 3.6% in our trauma patient population. The newly developed antibodies post-MTP are considered clinically significant, meaning they can cause hemolysis if exposed to donor red blood cells containing those antigens. Blood products should be given preferentially over crystalloids to acutely bleeding patients to prevent ischemic injury during an MTP activation despite the risk of alloimmunization. In our single-institution study, the alloimmunization rate in massive transfusions where patients receive uncrossmatched red blood cells is similar to those receiving crossmatched red blood cells.

HLA Class II regulation of immune response in sickle cell disease patients: Susceptibility to red blood cell alloimmunization (systematic review and meta-analysis).

Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody testing. RBC alloimmunization to RBC antigens is a frequently encountered complication seen in chronically transfused patients. Genetic factors such as the human leukocyte antigen (HLA) are known to influence and regulate immune responses. HLAs are highly polymorphic and play an essential role in regulating immune responses, including RBC alloimmunization. The aim of this study was to conduct a systematic review and meta-analysis to evaluate the association between HLA Class II allelic polymorphisms with the possible risk of developing RBC alloantibodies. Four databases were systematically searched for relevant studies between the years 2000 and 2021 following the PRISMA guidelines. Four articles met the eligibility and quality criterion, and three alleles, HLA-DRB1*04, HLA-DRB1*15 and HLA-DQB1*03, that were found to be potentially associated with an increased risk in alloantibody formation were included. The primary outcome measure was alloimmunization by RBC antigen exposure in multiply transfused SCD patients. The total estimate of alloimmunization of the SCD patients was 2.33 (95% CI, 1.58-3.44), demonstrating susceptibility to RBC alloantibody formation. Heterogeneity between the studies was insignificant, suggesting the differences associated with random sampling errors. The results showed that SCD patients carry an increased risk of producing RBC alloantibodies. A strategy to prevent RBC alloimmunization is genotyping for genetically susceptible SCD patients receiving multiple transfusions. Early identification of genetic variants that can potentially increase the risk of RBC alloimmunization could aid in the screening process and selection of phenotypically matched RBC units.

Transfusion support for patients with sickle cell disease

Red blood cell (RBC) transfusion is an essential treatment for many patients with sickle cell disease (SCD), whose RBCs express hemoglobin S (HbS), a mutated form of hemoglobin A (HbA). Transfusion goals include increasing blood oxygen carrying capacity and decreasing the relative amount of HbS to HbA to mitigate vaso-occlusion in small blood vessels. In situations where correction of severe anemia and reduction in HbS may be achieved without removal of RBCs, simple transfusion may be utilized. Partial manual RBC exchange, which removes blood containing HbS by phlebotomy and replaces with donor blood transfusion sequentially allows for larger changes in the ratio of HbS to HbA when compared to simple transfusion. Automated RBC exchange by apheresis is useful in situations where a rapid and drastic HbS reduction is indicated. Vascular access is an important consideration for transfusion. Although peripheral access may be sufficient, central venous catheters and implantable venous access devices may be necessary for adequate access over time. Blood bank considerations include adequate RBC antigen matching to mitigate the risk of RBC alloimmunization, of which patients with SCD are at risk of developing. Transfusion may be utilized in efforts to intervene in the evolution of potentially life-threatening complications of SCD such as acute stroke, severe acute anemia and acute chest syndrome. Transfusion is also useful in several non-acute settings, such as stroke prevention, pregnancy, pre-surgery, and transfusion support for curative therapies. Individualized treatment plans are an essential component of patient care. Continuous evaluation of clinical indications and evolution of guidelines will continue to optimize care for patients with SCD.

Phenotyping and Genotyping of HNA: Prevalence, Risk of Alloimmunization, and HNA Incompatibilities in Indians

Background: Antibodies to human neutrophil alloantigens (HNA) are involved in the pathophysiology of several clinical conditions including transfusion-related acute lung injury (TRALI), alloimmune and autoimmune neutropenia, and febrile nonhemolytic transfusion reactions leading to neutropenia. The cognate antigens are polymorphic structures expressed on several glycoproteins on the neutrophils, i.e., antigens HNA-1a, -1b, -1c, and -1d on Fc-γ-receptor IIIb; HNA-2 on CD177; HNA-3a and -3b on choline transporter-like protein 2; HNA-4a and -4b on CD11b/αM subunit of the αMβ2-integrin (CD11b/CD18, Mac-1, CR3); and HNA-5a and -5b on αL-subunit (CD11a) of the αLβ2 integrin (CD11a/CD18), leukocyte function associated molecule (LFA)-1. Currently, there is a lacuna of diagnostic methods for detection of HNA in India. This study aimed to determine the HNA frequencies in Indians, estimate the risk of alloimmunization, and prepare typed neutrophil panels, which can be used to detect HNA antibodies in neutropenia cases. Material and Methods: EDTA blood samples were collected from random 1,054 blood donors. HNA-2 was phenotyped on fresh EDTA samples using FITC labelled monoclonal anti-CD177 by flowcytometry. HNA-1 (FCGR3B) genotyping was carried out by DNA sequencing and PCR-RFLP. Antigens of HNA-3 (SLC44A2) and HNA-5 (ITGAL) were genotyped by PCR-RFLP using TaqαI and Bsp1286I restriction enzymes, respectively, while HNA-4 (ITGAM) was genotyped by PCR-SSP. Results: Allele frequencies of FCGR3B*01, FCGR3B*02, and FCGR3B*03 were found to be 0.433, 0.444, and 0.087, respectively. FCGR3B*01+*02+*03− was the most common genotype (33.78%). Ten individuals showed deficiency of FCGR3B individuals, while 23 showed hyperexpression, i.e., FCGR3B*01+*02+*03+. FCGR3B*04and *05 occurred with a frequency of 0.002 and 0.024. HNA-2 was found to be a high frequency antigen occurring in 98.8% population. Four percent individuals showed atypical expression of CD177 on their neutrophils. Allele frequencies of SLC44A2*01 and SLC44A2*02were 0.812 and 0.188, respectively, and that of ITGAM*01, ITGAM*02, ITGAL*01, and ITGAL*02 were 0.9546, 0.0454, 0.2372, and 0.7628, respectively. Conclusion: This is the first study in India to report the frequencies of HNA among blood donors. Typed neutrophil panels identified in the present study will enable us to investigate suspected cases of immune neutropenia in future.

Frequency of Extended Red Cell Antigen Phenotype Among Patients of Hematological Diseases: A Single Center Study.

BackgroundAlloimmunization of erythrocytes is a major problem in patients with hematological diseases that require frequent blood transfusions. Matching of extended red cell antigens of Kell, MNS, Kidd, and Duffy can decrease the risk of alloimmunization. Hence, in this study, the frequencies of the extended red cell phenotypes were explored.ObjectiveTo find out the frequency of extended red blood cell antigen phenotypes among patients with hematological diseases.MethodsThis cross-sectional research study was performed on 488 patients diagnosed with hematological diseases who required blood transfusion at the National Institute of Blood Disease and Bone Marrow Transplantation Karachi for a period of 1.42 years from November 2019 to March 2021. The blood of patients was analyzed for antigen phenotypes of different blood group systems including Kell, MNS, Kidd, and Duffy. The data obtained were interpreted.ResultsAmong the 488 patients, 284 (58.20%) patients were male, and 204 (41.80%) patients were female with a mean age of 8.1 years. Beta thalassemia was the most common hematological disease reported in 354 (72.5%) of the patients. The most common blood group was O positive reported in 182 (37.3%) of the patients followed by B positive blood group in 124 (25.4%). The frequencies of extended red cell antigen phenotypes in the patients were K antigen 14 (2.9%), Kpa antigen 26 (5.3%), Kpb antigen 424 (86.9%), Fya antigen 360 (73.8%), Fyb antigen 260 (53.3%), Jka antigen 294 (60.2%), Jkb antigen 326 (66.8%), M antigen 410 (84.0%) and N antigen 306 (62.7%).ConclusionBeta thalassemia was the most common hematological disease followed by iron deficiency anemia, aplastic anemia, and acute leukemia. Patients with hematological diseases had a higher prevalence of Kpb antigen followed by M, Fya, Jkb, N, Jka, Fyb, Kpa, and K antigen. O positive was the most frequent blood group followed by B positive, A positive and AB positive blood group.

Risks and Benefits of Prophylactic Transfusion before Cholecystectomy in Sickle Cell Disease.

Preoperative transfusion (PT) reduces acute postoperative vaso-occlusive events (VOE) in sickle cell disease (SCD), but exposes patients to alloimmunization, encouraging a recent trend towards transfusion sparing. The aim of this study was to investigate the benefit–risk ratio of PT before cholecystectomy on the occurrence of postoperative VOE. Adult SCD patients who underwent cholecystectomy between 2008 and 2019 in our center were included. Patients’ characteristics, collected retrospectively, were compared according to PT. A total of 79 patients were included, 66% of whom received PT. Gallbladder histopathology found chronic cholecystitis (97%) and gallstones (66%). Transfused patients underwent more urgent surgeries and had experienced more painful vaso-occlusive crises (VOC) in the month before surgery (p = 0.05). Four (8.5%) post-transfusion alloimmunizations occurred, and two of them caused a delayed hemolytic transfusion reaction (DHTR) (4.3%). The occurrence of postoperative VOE was similar between the groups (19.2% vs. 29.6%, p = 0.45). Though not statistically significant, a history of hospitalized VOC within 6 months prior to surgery seemed to be associated to postoperative VOE among non-transfused patients (75% vs. 31.6%, p = 0.10). PT before cholecystectomy exposes to risks of alloimmunization and DHTR that could be avoided in some patients. Recent VOCs appear to be associated with a higher risk of postoperative VOE and prompt the preemptive transfusion of these patients.

HLA-DRB1 and cytokine polymorphisms in Brazilian patients with myelodysplastic syndromes and its association with red blood cell alloimmunization.

This study aimed investigate association of HLA-DRB1 and cytokine polymorphisms with red blood cell(RBC) alloimmunization in Brazilian Myelodysplastic syndrome(MDS) patients with prior exposure to RBC transfusion. MDS patients are at risk RBC alloimmunization due to chronic RBC transfusion. However, differences in immune response of MDS transfused patients are not completely known. A retrospective cohort of 87 polytransfused patients with MDS including 28 alloimmunized (PA) and 59 non-alloimmunized (PNA) was evaluated in three Brazilian reference hospitals. HLA-DRB1genotype was performed by polymerase chain reaction (PCR)-SSOP (Luminex platform) and cytokine polymorphisms analysed by PCR and TaqMan assays. While HLA-DRB1 allele frequencies did not differ between groups, IL17A 197G > A SNP and IL4 polymorphisms showed significant correlation with RBC alloimmunization. IL17A 197A allele A and AA genotype were significantly more frequent in PA than PNA(A, 46.4% versus 27.1%, p= 0.012; OR=2.3; 95%CI=1.1-4.9; AA, 25% versus 6.8%, p= 0.041; OR=6.2; 95%CI 1.3-30.8). Moreover, significant association of alloimmunization to Rh antigens with IL17A 197A allele and AA genotype was also identified in PA group(A, 45% versus 27.1%, p= 0.036; OR=2.5; 95% CI 1.1-5.7; AA, 30% versus 6.8%, p= 0.042; OR=7.9; 95%CI 1.5-42.3). Genotype A1A2 of IL4 intron 3 was overrepresented in PA(50% versus 16.9%, p= 0.009; OR=4.97; 95%CI 1.6-15.5). Similarly, IL4-590 CT genotype was overrepresented in PA(53.6% versus 28.8%, p= 0.049; OR=3.3; 95%CI 1.2-9.3). This study showed no association regarding HLA-DRB1 alleles for RBC alloimmunization risk or protection, however the IL17A 197G>A, IL4 intron 3 and IL4 590C>T SNP was significantly associated to RBC alloimmunization risk in this cohort of Brazilian MDS patients.

P1623: ROLE OF HLA GENES IN DEVELOPMENT OF HLA-ALLOIMMUNIZATION IN BLOOD RECIPIENTS

Background: The main adverse effects of HLA-alloimmunization are transfusion failure and the need for additional platelet transfusions, febrile reactions, and the threat of fatal bleeding. The individual prediction of the risk of alloimmunization remains an unresolved problem. It seems relevant to study the relationship between the HLA genotype and the probability of alloimmunization of recipients as a result of blood transfusions. Aims: Assess the genetic predisposition of recipients to the development of HLA alloimmunization. Methods: Immunohematological and genetic studies were performed in 61 patients (22 men and 39 women) who received from 6 to 32 transfusions of blood components (median 11) during the previous treatment in a hematology clinic in 2019-2021. All blood components were leukoreduced. Patient age ranged from 3 to 78 years (median 48 years). Acute leukemia was diagnosed in 34 patients, myelodysplastic syndrome - in 10, aplastic anemia - in 8, other blood diseases - in 9. Typing of HLA DRB1, DQA1, DQB1 gene was performed by real-time polymerase chain reaction using equipment and reagents from DNA- technology (Russia). Statistical analysis was performed using the chi-square test. Results: Based on the results of the study of antilymphocyte antibodies, patients were divided into two groups: HLA-nonimmunized (n=31) and HLA-immunized (n=30). The Panel Reactive Antibody in 3 out of 30 alloimmunized patients was 25-49%, in 12 - 50-74%, in 15 patients - 75-100%. When analyzing the results of immunogenetic examination, statistical differences were established in the frequency of detection of HLA-alleles and haplotypes in the genotypes of HLA-alloimmunized and nonimmunized recipients (Table). Table. - Frequency of detection of HLA-DRB1-DQA1-DQB1 haplotypes in HLA-alloimmunized and HLA-non-alloimmunized patients HLA-DRB1-DQA1-DQB1 haplotypes Frequency of detection of HLA haplotypes p HLA-nonalloimmunized patients, n=31 HLA- alloimmunized patients, n=30 абс. % абс. DRB1*15-DQA1*01:02-DQB1*06:02-8 14 45.2 7 23.3 0.12 DRB1*01-DQA1*01:01-DQB1*05:01 12 38.7 9 30 0.65 DRB1*03-DQA1*05:01-DQB1*02:01 2 6.5 8 26.7 0.07 DRB1*04-DQA1*03:01-DQB1*03:02 1 3.2 9 30 0.01 DRB1*07-DQA1*02:01-DQB1*02:01 4 12.9 6 20 0.69 DRB1*13-DQA1*01:03-DQB1*06:02-8 3 9.7 7 23.3 0.27 DRB1*16-DQA1*01:02-DQB1*05:02 6 19.4 0 0 0.03 DRB1*11-DQA1*05:01-DQB1*03:01 3 9.7 4 13.3 0.96 Summary/Conclusion: A genetically determined predisposition to the development of HLA-alloimmunization as a result of blood transfusions is associated with the presence of HLA-alleles DRB1*04, DQA1*03:01, DQA1*05:01 and HLA-haplotype DRB1*04-DQA1*03:01-DQB1*03:02 in the genotypes of recipients. The probability of antibody production is reduced in patients with HLA-alleles DRB1*16, DQA1*01:02, DQB1*05:02 and HLA-haplotype DRB1*16-DQA1*01:02-DQB1*05:02.

Investigation of Dombrock Blood Group Alleles and Genotypes among Saudi Blood Donors in Southwestern Saudi Arabia.

The Dombrock (DO) blood group system has two primary antigens, Doa and Dob, which can cause delayed hemolytic transfusion reactions. The paucity of specific monospecific antibodies can hamper the typing based on these antigens. Thus, blood group genotyping (BGG) was investigated as a possible solution. Sequence-specific primers were designed to target a single nucleotide polymorphism (rs11276) on the ART4 gene encoding the DO*A and DO*B alleles. Blood samples (n = 150) from randomly selected volunteer donors were used. DNA was extracted and resulting PCR products were purified and sequenced. The allelic frequencies of DO*A and DO*B were (n = 122, 40.67%) and (n = 178, 59.33%), respectively. The distributions of DO genotypes were as follows: DO*A/DO*A (n = 20), 13.33%; DO*B/DO*B (n = 48), 32.00%; and DO*A/DO*B (n = 82), 54.67%. In conclusion, this study reports on the allelic frequencies of DO*A and DO*B of the DO blood group system in Jazan Province, Kingdom of Saudi Arabia. Furthermore, this study reports on the prevalence of each genotype, of which DO*A/DO*B was the most abundant. This study contributes significantly to build the current blood donor database in Southwestern Saudi Arabia. Moreover, it may assist in providing safe blood to polytransfused patients and reduce the risk of the red cell alloimmunization.

Retention of functional mitochondria in mature red blood cells from patients with sickle cell disease.

Sickle cell disease (SCD) is an inherited blood disorder characterized by sickled red blood cells (RBCs), which are more sensitive to haemolysis and can contribute to disease pathophysiology. Although treatment of SCD can include RBC transfusion, patients with SCD have high rates of alloimmunization. We hypothesized that RBCs from patients with SCD have functionally active mitochondria and can elicit a type 1 interferon response. We evaluated blood samples from more than 100 patients with SCD and found elevated frequencies of mitochondria in reticulocytes and mature RBCs, as compared to healthy blood donors. The presence of mitochondria in mature RBCs was confirmed by flow cytometry, electron microscopy, and proteomic analysis. The mitochondria in mature RBCs were metabolically competent, as determined by enzymatic activities and elevated levels of mitochondria-derived metabolites. Metabolically-active mitochondria in RBCs may increase oxidative stress, which could facilitate and/or exacerbate SCD complications. Coculture of mitochondria-positive RBCs with neutrophils induced production of type 1 interferons, which are known to increase RBC alloimmunization rates. These data demonstrate that mitochondria retained in mature RBCs are functional and can elicit immune responses, suggesting that inappropriate retention of mitochondria in RBCs may play an underappreciated role in SCD complications and be an RBC alloimmunization risk factor.

Prenatal Diagnosis and Management of Thrombocytopenia-Absent Radius Syndrome.

Prenatal Diagnosis and Management of Thrombocytopenia-Absent Radius Syndrome.

Warm autoimmune hemolytic anemia with anti-e specificity: A case report

Warm autoimmune hemolytic anemia is a rare condition characterized by warm autoantibody destruction of red blood cells. Antibody specificity cannot be determined in most cases and an apparent autoantibody specificity to a specific antigen is rarely seen. Here we present a case of a 43-year-old female patient presenting with acute small bowel obstruction and requiring an exploratory laparotomy. However, laboratory investigations showed evidence of intravascular hemolysis with normocytic normochromic anemia, reticulocytosis, elevated bilirubin and lactate dehydrogenase levels, and low haptoglobin level. Two units of packed red blood cells were requested. Blood bank investigations including antibody screening, antibody identification panel, direct coombs testing with polyspecific and monospecific anti-human globulin, extended rhesus phenotype, and confirmatory elution testing revealed an IgG autoantibody with anti-e specificity. No compatible units with Rh (e) - positive units were found. However, Rh (e) - negative units’ transfusion was associated with a risk of alloimmunization and a decision of two least incompatible units was taken. So, an anti-e IgG autoantibody was identified which is a rare and challenging clinical condition in terms of diagnosis and transfusion.

Prevalence of Rh and K phenotypes among blood donors from different ethnicities in Samtah (Southwestern Region) Saudi Arabia.

Rh and Kell blood group systems are amongst the most important blood group systems; being highly immunogenic after ABO system. The aim of this study was to evaluate the frequencies of Rh antigens, haplotypes and K antigen among blood donors belonging to various ethnicities in Samtah, Jazan, Saudi Arabia. This study was conducted during January 2019 and August 2020 at Samtah General Hospital, Samtah. Records of all blood donors recruited during this period were included for data acquisition. A total of 4977 blood donors' records were reviewed and data were analysed. A total of 3863 donors' results were considered in the final analysis. In comparison to Saudi blood donors, C antigen was less frequent in Sudanese donors (69.7% and 34.0%), the c antigen was less frequent in Indian (79.2% and 59.3%) and Philippine (79.2% and 40.0%) donors and more frequent in Sudanese (79.2% and 97.9%) donors, the E antigen was less frequent in Yemini (27.0% and 19.5%) and the e antigen was more frequent in Yemini (96.7% and 99.2%) donors. The DcE haplotype was less frequent (3.1% and 0.7%) and the ce haplotype was more frequent (4.3% and 7.6%) in Yemini donors. The K antigen was less frequent in Pakistani (11.9% and 4.1%; p = .041) and Indian (11.9% and 1.9%; p = .023) donors. Rh and K antigens showed marked variations in their frequencies among blood donors of different ethnicities. Utilization of blood from various ethnicities warrant extended phenotyping of Rh and K antigens to avoid the risk of alloimmunization in multiply transfused patients.

Obstetric and Newborn Weak D-Phenotype RBC Testing and Rh Immune Globulin Management Recommendations: Lessons From a Blinded Specimen-Testing Survey of 81 Transfusion Services.

Modern RHD genotyping can be used to determine when patients with serologic weak D phenotypes have RHD gene variants at risk for anti-D alloimmunization. However, serologic testing, RhD interpretations, and laboratory management of these patients are quite variable. To obtain interlaboratory comparisons of serologic testing, RhD interpretations, Rh immune globulin (RhIG) management, fetomaternal hemorrhage testing, and RHD genotyping for weak D-reactive specimens. We devised an educational exercise in which 81 transfusion services supporting obstetrics performed tube-method RhD typing on 2 unknown red blood cell challenge specimens identified as (1) maternal and (2) newborn. Both specimens were from the same weak D-reactive donor. The exercise revealed how participants responded to these different clinical situations. Of reporting laboratories, 14% (11 of 80) obtained discrepant immediate-spin reactions on the 2 specimens. Nine different reporting terms were used to interpret weak D-reactive maternal RhD types to obstetricians. In laboratories obtaining negative maternal immediate-spin reactions, 28% (16 of 57) performed unwarranted antiglobulin testing, sometimes leading to recommendations against giving RhIG. To screen for excess fetomaternal hemorrhage after a weak D-reactive newborn, 47% (34 of 73) of reporting laboratories would have employed a contraindicated fetal rosette test, risking false-negative results and inadequate RhIG coverage. Sixty percent (44 of 73) of laboratories would obtain RHD genotyping in some or all cases. For obstetric and neonatal patients with serologic weak D phenotypes, we found several critical problems in transfusion service laboratory practices. We provide recommendations for appropriate testing, consistent immunohematologic terminology, and RHD genotype-guided management of Rh immune globulin therapy and RBC transfusions.

Toward in Vitro Production of Platelet from Induced Pluripotent Stem Cells.

Platelets (PLTs) are small anucleate blood cells that release from polyploidy megakaryocytes(MKs). PLT transfusion is standard therapy to prevent hemorrhage. PLT transfusion is donor-dependent way which have limitations including the inadequate donor blood supply, poor quality, and issues related to infection and immunity. Overcoming these obstacles is possible with in vitro production of human PLTs. Currently several cells have been considered as source to in vitro production of PLTs such as hematopoietic stem cells (HSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, HSCs are a limited source for PLT production and large-scale expansion of HSC-derived PLT remains difficult. Alternative sources can be ESCs which have unlimited expansion capacity. But ESCs have ethical issues related to destroying human embryos. iPSCs are considered as an ideal unlimited source for PLT production. They are ableto differentiate into any cells and have thecapacityofself-renewal. Moreover, iPSCs can be acquired from any donor and easily manipulated. Due to new advances in development of MK cell lines, bioreactors, feeder cell-free production and the ability of large scale generation, iPSC-based PLTs are moving toward clinical applicability and considering the minimal risk of alloimmunization and tumorigenesis of these products, there is great hopefulness they will become the standard source for blood transfusions in the future. This review will focus on how to progress of in vitro generation of PLT from stem cell especially iPSCs and some of the successful strategies that can be easily used in clinic will be described.

Erythrocyte Antibody Due to Alloimmunization in Repeated Transfusion: A Meta-Analysis

BACKGROUND: Blood transfusion is one form of life-saving efforts to improve health. Each individual will experience a different transfusion reaction. Having a history of repeated transfusions increases the risk of alloimmunization leading to the development of erythrocyte alloantibodies. AIM: This study is a meta-analysis of various studies on erythrocyte antibodies due to alloimmunization in repeated transfusion. METHODS: Literatures were searched through the PubMed, DOAJ, and Google Scholar databases using the keywords “repeated transfusion,” “alloimmunization,” and “erythrocyte antibody” published in 2017 - 2021. All identified articles were then screened for relevance as well as duplication according to inclusion and exclusion criteria. Then, the articles were analyzed using software review manager 5.4 and software comprehensive meta-analysis (CMA) version 3. RESULTS: A total of seven articles were included in this study. Based on the analysis, we found that there was no association between alloimmunization in repeated transfusions with erythrocyte antibodies based on gender (pooled odds ratio 1.00 [95% CI 0.70 - 1.42]. CONCLUSION: Alloimmunization on repeated transfusion was not significantly associated with erythrocyte antibody based on gender.

Weak D type 42: Antigen density and risk of alloimmunization in the province of Québec.

A high proportion of suspected weak D patients referred to Héma-Québec were genotyped as weak D type 42 (368/2105, 17.5%). These patients are currently considered D with regard to RhD immunoprophylaxis in pregnancy and transfusion. The goal of this study was to retrospectively evaluate the risk of alloimmunization in weak D type 42 patients and to characterize their RhD surface molecule expression on red blood cells (RBCs) in comparison to other weak D types (1, 2 and 3). A retrospective analysis using the weak D type 42 patients' medical data to verify potential anti-D alloimmunization events was conducted. Quantitative analyses using flow cytometry were also performed on RBCs to quantify the cell surface density of the D antigen. Data on 215 subjects with weak D type 42 were reviewed. None developed immune allo-anti-D; three had definite exposure to D+ red cells and 41 had possible exposure through pregnancy. Flow cytometry analysis showed that weak D types 1, 2, 3 and 42 had relative antigen densities of 2.7%, 2.2%, 8.1% and 3.6%, respectively, with R1R2 red cells referencing 100% density. The estimated antigen density range of weak D type 42 was 819-1104 sites per RBC. Our retrospective alloimmunization data analysis and antigen density study establish a basis for the consideration of a weak D type 42 individual as D+. This consideration would allow for a targeted reduction of RhD immunoprophylaxis in pregnancy and the unjustified use of D- units for transfusion.