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Transfusion Feb 2011In April 2010, a working group sponsored by the National Heart, Lung, and Blood Institute was assembled to identify research strategies to improve our understanding of...
In April 2010, a working group sponsored by the National Heart, Lung, and Blood Institute was assembled to identify research strategies to improve our understanding of alloimmunization caused by the transfusion of allogeneic blood components and to evaluate potential approaches to both reduce its occurrence and manage its effects. Significant sequelae of alloimmunization were discussed and identified, including difficulties in maintaining chronic transfusion of red blood cells and platelets, hemolytic disease of the newborn, neonatal alloimmune thrombocytopenia, and rejection of transplanted cells and tissues. The discussions resulted in a consensus that identified key areas of future research and developmental areas, including genetic and epigenetic recipient factors that regulate alloimmunization, biochemical specifics of transfused products that affect alloimmunization, and novel technologies for high-throughput genotyping to facilitate extensive and efficient antigen matching between donor and recipient. Additional areas of importance included analysis of unappreciated medical sequelae of alloimmunization, such as cellular immunity and its effect upon transplant and autoimmunity. In addition, support for research infrastructure was discussed, with an emphasis on encouraging collaboration and synergy of animal models biology and human clinical research. Finally, training future investigators was identified as an area of importance. In aggregate, this communication provides a synopsis of the opinions of the working group on the above issues and presents both a list of suggested priorities and the rationale for the topics of focus. The areas of research identified in this report represent potential fertile ground for the medical advancement of preventing and managing alloimmunization in its different forms and mitigating the clinical problems it presents to multiple patient populations.
Topics: Adult; Animals; Antigens, Human Platelet; Blood Group Antigens; Blood Group Incompatibility; Cooperative Behavior; Female; Forecasting; Health Priorities; Humans; Infant, Newborn; Isoantibodies; Lymphocyte Subsets; Male; Models, Animal; National Heart, Lung, and Blood Institute (U.S.); Pregnancy; Research Personnel; Thrombocytopenia, Neonatal Alloimmune; Transfusion Reaction; Transplantation Immunology; United States
PubMed: 21251006
DOI: 10.1111/j.1537-2995.2010.03024.x -
Transfusion May 2023Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are...
BACKGROUND
Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are collected in plasma which may contain ABO isohemagglutinins, it remains controversial as to whether ABO non-identical platelet transfusions could potentially pose harm and/or have reduced efficacy.
STUDY DESIGN AND METHODS
The large 4-year publicly available Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) database was used to investigate patient outcomes associated with ABO non-identical platelet transfusions. Outcomes included mortality, sepsis, and subsequent platelet transfusion requirements.
RESULTS
Following adjustment for possible confounding factors, no statistically significant association between ABO non-identical platelet transfusion and increased risk of mortality was observed in the overall cohort of 21,176 recipients. However, when analyzed by diagnostic category and recipient ABO group, associations with increased mortality for major mismatched transfusions were noted in two of eight subpopulations. Hematology/Oncology blood group A and B recipients (but not group O) showed a Hazard Ratio (HR) of 1.29 (95%CI: 1.03-1.62) and intracerebral hemorrhage group O recipients (but not groups A and B) showed a HR of 1.75 (95%CI: 1.10-2.80). Major mismatched transfusions were associated with increased odds of receiving additional platelet transfusion each post-transfusion day (through day 5) regardless of the recipient blood group.
DISCUSSION
We suggest that prospective studies are needed to determine if specific patient populations would benefit from receiving ABO identical platelet units. Our findings indicate that ABO-identical platelet products minimize patient exposure to additional platelet doses.
Topics: Humans; Platelet Transfusion; Blood Platelets; Retrospective Studies; ABO Blood-Group System; Blood Group Incompatibility; Transfusion Reaction
PubMed: 36994786
DOI: 10.1111/trf.17319 -
American Journal of Transplantation :... Apr 2012
Topics: ABO Blood-Group System; Antibodies; B-Lymphocytes; Blood Group Incompatibility; Female; Graft Rejection; Heart Transplantation; Hemagglutinins; Humans; Male
PubMed: 22233401
DOI: 10.1111/j.1600-6143.2011.03913.x -
Vox Sanguinis Nov 2022The field of transfusion medicine started out with whole blood transfusion to treat severe anaemia and other deficiencies, and then transitioned to component therapy,...
BACKGROUND AND OBJECTIVES
The field of transfusion medicine started out with whole blood transfusion to treat severe anaemia and other deficiencies, and then transitioned to component therapy, largely leaving the practice, and experiences, of whole blood transfusions behind. Currently, the field is circling back and whole blood is gaining ground as an alternative to massive transfusion protocols.
MATERIALS AND METHODS
Herein we describe a severely anaemic paroxysmal nocturnal haemoglobinuria (PNH) patient initially suspected of suffering from renal haemorrhage, receiving a standard low-titre group O whole blood transfusion during pre-hospital transportation.
RESULTS
Following the transfusion, the patient suffered a clinically unmistakable haemolytic transfusion reaction requiring supportive treatment in the intensive care unit. Clinical observations are consistent with an acute haemolytic reaction. The haemolysis was likely due to minor incompatibility between the plasma from the transfused whole blood and the patient's PNH red cells. Recovery was uneventful.
CONCLUSION
This revealed an unappreciated contraindication to minor incompatible whole blood transfusion, and prompted a discussion on the distinction between whole blood and erythrocyte concentrates, the different indications for use and the importance of emphasizing these differences. It also calls attention to patient groups where minor incompatibility can be of major importance.
Topics: Humans; Hemoglobinuria, Paroxysmal; Blood Transfusion; Blood Group Incompatibility; ABO Blood-Group System; Transfusion Reaction; Hemolysis
PubMed: 36102159
DOI: 10.1111/vox.13354 -
Blood Transfusion = Trasfusione Del... Sep 2022The impact of ABO incompatibility on the outcome of hematopoietic stem cell transplantation (HSCT) is still debated. We report the results of a prospective,...
BACKGROUND
The impact of ABO incompatibility on the outcome of hematopoietic stem cell transplantation (HSCT) is still debated. We report the results of a prospective, single-center study evaluating the impact of ABO mismatch on the development of immediate and late immuno-hematological complications, and the efficacy of the protocol used at the "Sapienza" University (Rome, Italy) to manage ABO incompatibility in patients undergoing HSCT.
MATERIALS AND METHODS
From January 2013 to December 2016, we prospectively analyzed all patients undergoing HSCT. Graft manipulation or desensitization strategies were used according to ABO incompatibility, donor sex and donor transfusion history. Red blood cell and platelet transfusions were given based on immunohematological features.
RESULTS
From January 2013 to December 2016, 104 consecutive patients underwent HSCT from a matched related donor (29.81%), matched unrelated donor (53.58%), cord blood (1.9%) or haploidentical donor (14.42%). Forty-nine patients (47%) were ABO-identical and 55 (53%) ABO-incompatible (23 major, 25 minor, 7 bidirectional). Donor engraftment, graft failure or other complications did not differ between ABO compatible or incompatible patients. ABO incompatibility did not show a significant impact on graft-versus-host disease, overall survival or disease-free survival. Factors associated with the need for prolonged red blood cell support were ABO incompatibility (p=0.0395), HLA disparity between donor and recipient (p=0.004) and the onset of hemorrhagic cystitis (p=0.015). In multivariate analysis HLA disparity was the only statistically significant condition (p=0.004).
DISCUSSION
ABO incompatibility does not represent a barrier to allogeneic HSCT. It is, however, associated with prolonged transfusion requirements. Close immunohematological monitoring, as a shared standard procedure, allows appropriate transfusion support to be provided and limits post-HSCT immuno-hematological complications.
Topics: ABO Blood-Group System; Blood Group Incompatibility; Hematopoietic Stem Cell Transplantation; Humans; Prospective Studies; Retrospective Studies; Transfusion Reaction; Transplantation, Homologous; Treatment Outcome
PubMed: 35543676
DOI: 10.2450/2022.0289-21 -
International Journal of Epidemiology Aug 2014Although the risks of adverse pregnancy outcomes associated with anti-D antibodies are well-recognized, much less is known concerning alloimmunization with other red...
BACKGROUND
Although the risks of adverse pregnancy outcomes associated with anti-D antibodies are well-recognized, much less is known concerning alloimmunization with other red blood cell antibodies detected during routine maternal screening. To date, most reports of adverse pregnancy outcomes associated with non-anti-D antibodies have been from small case studies. The aim of this study was to examine the associations of maternal alloimmunization with specific red blood cell antibodies and the risks of preterm birth and stillbirth in the Swedish population.
METHODS
All antibody screening, outcome and covariate data were obtained through linkages of Swedish national health and data registers. Follow-up in these population-based registers was available up to 31 December 2002. The final study sample consisted of 1,022,569 singleton births from 668,952 mothers during 1987-2002.
RESULTS
In total, 1.3% of the 1,022,569 study pregnancies were alloimmunized. In adjusted logistic regression models, compared with having no antibodies, alloimmunization with anti-D, anti-E, anti-C and anti-c was associated with increased risk of both stillbirth and preterm birth. In addition, anti-Kell was associated with increased risk of preterm birth and anti-Lea with increased risk of stillbirth. Compared with firstborn children, risk of preterm birth associated with alloimmunization was greater in subsequent births
CONCLUSIONS
In the largest study to date, alloimmunization with Rhesus, K- and -Lea red blood cell antibodies increased the risk of preterm birth and/or stillbirth. The association of anti-Lea with stillbirth was an unexpected finding. Further study of the consequences of non-anti-D alloimmunization is warranted.
Topics: Adult; Blood Group Incompatibility; Erythrocytes; Female; Humans; Isoantibodies; Logistic Models; Male; Membrane Glycoproteins; Metalloendopeptidases; Pregnancy; Premature Birth; Rh Isoimmunization; Rho(D) Immune Globulin; Stillbirth; Sweden; Young Adult
PubMed: 24801308
DOI: 10.1093/ije/dyu079 -
Annals of Transplantation Oct 2020BACKGROUND Patients receiving ABO-incompatible (ABOi) or human leukocyte antigen (HLA)-incompatible (HLAi) kidney transplantation (KT) require potent immunosuppression...
BACKGROUND Patients receiving ABO-incompatible (ABOi) or human leukocyte antigen (HLA)-incompatible (HLAi) kidney transplantation (KT) require potent immunosuppression and are thus at a higher risk of infectious complications. We evaluated the clinical outcomes of KT stratified by ABO and HLA incompatibilities and identified the factors associated with the clinical outcomes. MATERIAL AND METHODS Recipients who underwent living-related KT between 2012 and 2017 were included and classified into 4 groups: ABO-compatible and HLA-compatible (ABOc/HLAc), HLA-incompatible (ABOc/HLAi), ABO-incompatible (ABOi/HLAc), and ABO-incompatible and HLA-incompatible (ABOi/HLAi). Cox proportional hazards regression analyses were carried out to evaluate the risk factors of acute rejection. Out of the 1732 patients who underwent KT, 1190, 131, 358, and 53 were in the ABOc/HLAc, ABOi/HLAc, ABOc/HLAi, and ABOi/HLAi groups, respectively. RESULTS The ABO/HLAi group showed the lowest 5-year graft survival rate (91.7%). Death-censored graft survival was not significantly different among the groups. The mortality rate from infections was significantly higher in the ABOi/HLAi group (7.5%) than the other groups. Antibody-mediated rejection-free graft survival was the lowest in the ABOi/HLAi group, with significant differences compared with the ABOi/HLAc group (P=0.02) and the ABOc/HLAi group (P=0.03). ABOi/HLAi (hazard ratio [HR], 2.63; 95% confidence interval [CI], 1.04-6.65; P<0.01) and combined infection (HR, 1.91; 95% CI, 1.45-2.51; P<0.01) were significant risk factors for acute rejection. CONCLUSIONS Patients with both ABO and HLA incompatibilities showed inferior rates of overall patient and graft survival due to infectious complications. Infection was a prominent risk factor of acute rejection following KT after adjusting for possible confounders including ABO and HLA incompatibility.
Topics: ABO Blood-Group System; Adult; Blood Group Incompatibility; Female; Graft Rejection; HLA Antigens; Humans; Infections; Kidney Transplantation; Living Donors; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Survival Rate; Treatment Outcome
PubMed: 33020465
DOI: 10.12659/AOT.927420 -
Transfusion Sep 2017The pathogenesis of alloimmunization is not well understood, and initiatives that aim to reduce the incidence of alloimmunization are generally expensive and either... (Review)
Review
BACKGROUND
The pathogenesis of alloimmunization is not well understood, and initiatives that aim to reduce the incidence of alloimmunization are generally expensive and either ineffective or unproven. In this review, we summarize the current medical literature regarding alloimmunization in the sickle cell disease (SCD) population, with a special focus on the financial implications of different approaches to prevent alloimmunization.
STUDY DESIGN AND METHODS
A review of EMBASE and MEDLINE data from January 2006 through January 2016 was conducted to identify articles relating to complications of SCD. The search was specifically designed to capture articles that evaluated the costs of various strategies to prevent alloimmunization and its sequelae.
RESULTS
Currently, there is no proven, inexpensive way to prevent alloimmunization among individuals with SCD. Serologic matching programs are not uniformly successful in preventing alloimmunization, particularly to Rh antigens, because of the high frequency of variant Rh alleles in the SCD population. A genotypic matching program could offer some cost savings compared to a serologic matching program, but the efficacy of gene matching for the prevention of alloimmunization is largely unproven, and large-scale implementation could be expensive.
CONCLUSIONS
Future reductions in the costs associated with genotype matching could make a large-scale program economically feasible. Novel techniques to identify patients at highest risk for alloimmunization could improve the cost effectiveness of antigen matching programs. A clinical trial comparing the efficacy of serologic matching to genotype matching would be informative.
Topics: Anemia, Sickle Cell; Blood Group Incompatibility; Blood Grouping and Crossmatching; Blood Transfusion; Cost-Benefit Analysis; Genotype; Humans; Transfusion Reaction
PubMed: 28653325
DOI: 10.1111/trf.14212 -
PloS One 2015Severe transfusion-related acute lung injury (TRALI) is often due to antibodies in blood components directed against human neutrophil antigen (HNA)-3a. This study aimed...
Severe transfusion-related acute lung injury (TRALI) is often due to antibodies in blood components directed against human neutrophil antigen (HNA)-3a. This study aimed to report the genotype frequencies of the HNA-3 system and to estimate the potential risk of HNA-3 incompatibility and alloimmunization in two Thai populations. Eight hundred DNA samples obtained from 500 unrelated healthy blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok and 300 samples from the Blood Bank, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand were included. HNA-3 genotyping was performed using an in-house polymerase chain reaction with sequence-specific primer (PCR-SSP) technique. The observed frequencies of the HNA-3a/3a, HNA-3a/3b, and HNA-3b/3b genotypes were 0.528, 0.380, and 0.092 in central Thais and 0.600, 0.350, and 0.050 in northern Thais, respectively. The frequencies were used to estimate HNA-3 incompatibility and risk of HNA-3a alloimmunization. The HNA-3 incompatibility in central Thais (33.28%) was higher than northern Thais (28.75%), corresponding to a significantly higher probability of HNA-3a alloimmunization (P<0.05) similar to Japanese and Chinese populations. This study showed the high risk of HNA-3 incompatibility and alloimmunization, especially in central Thai blood donors. A molecular-based identification of the HNA-3 genotype of female donors is suggested to reduce the risk of TRALI following plasma and whole blood allogeneic transfusion.
Topics: Asian People; Blood Donors; Blood Group Incompatibility; Female; Gene Frequency; Genotyping Techniques; Humans; Isoantibodies; Isoantigens; Membrane Glycoproteins; Membrane Transport Proteins; Polymorphism, Single Nucleotide; Risk Factors; Thailand
PubMed: 25608003
DOI: 10.1371/journal.pone.0116905 -
Biochemistry. Biokhimiia Jul 2015Natural anti-carbohydrate antibodies (NAbC) are antibodies that target glycans and are continuously produced without apparent external antigen stimulation. Clinically,... (Review)
Review
Natural anti-carbohydrate antibodies (NAbC) are antibodies that target glycans and are continuously produced without apparent external antigen stimulation. Clinically, NAbC are recognized by the adverse reactions to ABO mismatched blood transfusions or organ transplantation and the rejection of xenografts. These clinical effects do not reflect the biological functions of NAbC. However, they launch the possibility of using NAbC for boosting immunity in different clinical settings by means of: 1) expression of glycan antigens in elements that do not hold them to allow the binding and reactivity of existing NAbC; 2) removal of existing NAbC; 3) manipulation of the glycosylation pattern of NAbC.
Topics: Animals; Antibodies; Antigens; Blood Group Incompatibility; Carbohydrates; Glycosylation; Humans; Polysaccharides; Transplantation, Heterologous
PubMed: 26541998
DOI: 10.1134/S0006297915070044