Association between plasma proteome and pulmonary heart disease: A two-stage Mendelian randomization analysis.

Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome-wide association study in the INTERVAL study. The results were validated using a case-control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo-blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin-dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019-1.095, p = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (p = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.

Neonatal screening of ABO/RhD blood group and direct antiglobulin Coombs test. Experience of a single institution.

BACKGROUND: Evaluating the ABO/RhD blood group and the direct antiglobulin Coombs test (DAT) at birth is recommended good practice, but there is variability in its universal implementation. This study aims to show the comparative results in various variables of clinical impact during the hospital stay of neonates with positive DAT compared with those with negative DAT, based on the systematic detection of the ABO/RhD group and DAT at birth. METHODS: Newborns between 2017 and 2020 in a high-risk pregnancy care hospital were included. The ABO/RhD and DAT group was determined in umbilical cord samples or the first 24 hours of life. Demographic, maternal, and neonatal variables were recorded. The association between the variables was estimated using the odds ratio (OR). RESULTS: 8721 pairs were included. The DAT was positive in 239 newborns (2.7%), with the variables associated with positive PDC being maternal age > 40 years (OR: 1.5; 95% CI: 1.0 to 2.3), birth by cesarean section (1.4; 1.1-2.0), mother group O (6.4; 3.8-11.8), prematurity (3.6; 2.6-5.0), birth weight < 2500 g (2.1; 1.6-2.8), newborn group A (15.7; 10.7-23.1) and group B (17.6; 11.4-27.2), hemoglobin at birth < 13.5 g/dl (4.5; 2.8-7.1) and reticulocytosis > 9% (1.9; 1.2 to 3.1). DISCUSSION: The frequency of neonatal positive PDC was 2.7%, with a significant association with maternal/neonatal incompatibility to the ABO and RhD group, with a substantial impact on various neonatal variables. These results support the policy of universal implementation at the birth of the ABO/RhD and DAT determination.

INTRODUCCIÓN: La determinación del grupo sanguíneo ABO/RhD y la prueba directa de Coombs (PDC) al nacimiento son una práctica recomendada, pero existe variabilidad en su implementación universal. Se presentan los resultados de la determinación al nacimiento del grupo ABO/RhD y la PDC en una cohorte institucional. MÉTODOS: Se incluyeron los recién nacidos entre 2017 y 2020 en un hospital de atención a embarazos de alto riesgo. Se determinó el grupo ABO/RhD y se realizó la PDC en muestras de cordón umbilical o en las primeras 24 horas de vida. Se registraron las variables demográficas, maternas y neonatales. Se estimó la asociación entre las variables mediante la razón de probabilidad (OR). RESULTADOS: Se incluyeron 8721 binomios. La PDC fue positiva en 239 recién nacidos (2.7%), siendo las variables asociadas a la PDC positiva la edad materna > 40 años (OR: 1.5;IC95%: 1.0-2.3), el nacimiento por vía cesárea (1.4; 1.1-2.0), la madre del grupo O (6.4; 3.8-11.8), la prematuridad (3.6; 2.6-5.0); el peso al nacer < 2500 g (2.1; 1.6-2.8); el neonato del grupo A (15.7; 10.7-23.1) o del grupo B (17.6; 11.4-27.2), la hemoglobina al nacer < 13.5 g/dl (4.5; 2.8-7.1) y la reticulocitosis > 9% (1.9; 1.2 a 3.1). DISCUSIÓN: La frecuencia de PDC positiva neonatal es del 2.7%, con asociación significativa la incompatibilidad materna/neonatal al grupo ABO y RhD, con impacto significativo en diversas variables neonatales. Estos resultados apoyan la política de implementación universal al nacimiento de la determinación de ABO/RhD y PDC.

Potential therapeutic targets for membranous nephropathy: proteome-wide Mendelian randomization and colocalization analysis.

Background: The currently available medications for treating membranous nephropathy (MN) still have unsatisfactory efficacy in inhibiting disease recurrence, slowing down its progression, and even halting the development of end-stage renal disease. There is still a need to develop novel drugs targeting MN. Methods: We utilized summary statistics of MN from the Kiryluk Lab and obtained plasma protein data from Zheng et al. We performed a Bidirectional Mendelian randomization analysis, HEIDI test, mediation analysis, Bayesian colocalization, phenotype scanning, drug bank analysis, and protein-protein interaction network. Results: The Mendelian randomization analysis uncovered 8 distinct proteins associated with MN after multiple false discovery rate corrections. Proteins related to an increased risk of MN in plasma include ABO [(Histo-Blood Group Abo System Transferase) (WR OR = 1.12, 95%CI:1.05-1.19, FDR=0.09, PPH4 = 0.79)], VWF [(Von Willebrand Factor) (WR OR = 1.41, 95%CI:1.16-1.72, FDR=0.02, PPH4 = 0.81)] and CD209 [(Cd209 Antigen) (WR OR = 1.19, 95%CI:1.07-1.31, FDR=0.09, PPH4 = 0.78)], and proteins that have a protective effect on MN: HRG [(Histidine-Rich Glycoprotein) (WR OR = 0.84, 95%CI:0.76-0.93, FDR=0.02, PPH4 = 0.80)], CD27 [(Cd27 Antigen) (WR OR = 0.78, 95%CI:0.68-0.90, FDR=0.02, PPH4 = 0.80)], LRPPRC [(Leucine-Rich Ppr Motif-Containing Protein, Mitochondrial) (WR OR = 0.79, 95%CI:0.69-0.91, FDR=0.09, PPH4 = 0.80)], TIMP4 [(Metalloproteinase Inhibitor 4) (WR OR = 0.67, 95%CI:0.53-0.84, FDR=0.09, PPH4 = 0.79)] and MAP2K4 [(Dual Specificity Mitogen-Activated Protein Kinase Kinase 4) (WR OR = 0.82, 95%CI:0.72-0.92, FDR=0.09, PPH4 = 0.80)]. ABO, HRG, and TIMP4 successfully passed the HEIDI test. None of these proteins exhibited a reverse causal relationship. Bayesian colocalization analysis provided evidence that all of them share variants with MN. We identified type 1 diabetes, trunk fat, and asthma as having intermediate effects in these pathways. Conclusions: Our comprehensive analysis indicates a causal effect of ABO, CD27, VWF, HRG, CD209, LRPPRC, MAP2K4, and TIMP4 at the genetically determined circulating levels on the risk of MN. These proteins can potentially be a promising therapeutic target for the treatment of MN.

Gene-Gene Interaction Between Factor-XI and ABO Genes in Cerebral Venous Thrombosis: The BEAST Study.

BACKGROUND AND OBJECTIVES: Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT. METHODS: Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status. RESULTS: We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA. DISCUSSION: Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.

Immuno-Hematologic Complexity of ABO-Incompatible Allogeneic HSC Transplantation.

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO incompatible. Immuno-hematologic investigations allow to estimate donor/recipient ABO mismatch and anti-A/B isohemagglutinin (IHA) titration in the pre-HSCT phase. Immediate hemolysis or delayed complications (passenger lymphocyte syndrome and pure red cell aplasia) can occur post HSCT. Some preventive measures take into consideration either decision-making algorithms based on the recipient's IHA titration or clinical protocols for the removal/reduction of IHAs through plasma exchange or immunoadsorption procedures. Product manipulation through red blood cell (RBC) and/or plasma depletion can also be taken into account. Currently, the best approach in the management of ABO-incompatible transplant is not defined in expert consensus documents or with solid evidence. In addition, the methods for IHA titration are not standardized. A transfusion strategy must consider both the donor's and recipient's blood group systems until the RBC engraftment catches on and ABO conversion (forward and reverse typing) is confirmed on two consecutive and independent samples. Therefore, ABO incompatibility in HSCT represents a demanding immuno-hematologic challenge and requires all necessary preventive measures, including the appropriate selection of ABO blood components for transfusion.

ABO and Rhesus blood groups and multiple health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. METHODS: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8-11), moderate (4-7), and low (0-3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). RESULTS: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. CONCLUSIONS: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.

The ABO blood group antigens in patients with oral lichenoid reaction.

Evaluating the association of ABO blood group with different delayed hypersensitivity reactions, such as oral lichenoid reaction (OLR), can provide a new perspective for clinical practice. Therefore, this study designed to investigate ABO blood group antigens in OLR patients. In this case-control study, the ABO blood group of 112 OLR patients and 117 individuals without oral lesions were included. Gender, age, characteristics of the lesions, medications and restorative materials recorded. Chi-square test used to compare the frequency of ABO blood groups in OLR patients with controls. The O blood group was significantly higher in OLR patients and all its subtypes. Also, there were significant relation between O blood group, and severity of lesions. The frequency of dysplasia was non-statistically significant higher in OLR patients with O blood group than other blood group. Based on the results of the present study, O blood group was significantly more in patients with lichenoid reaction than control group, and AB blood group was the lowest. Also, O blood group showed a positive association with the more severe form of OLR lesions and frequency of dysplasia.

[Feasibility Analysis of Establishing Combat Readiness Blood Bank Based on Low Titer Group O Whole Blood and Group A Plasma].

OBJECTIVE: To explore the feasibility of establishing combat readiness blood bank with low titer group O whole blood and group A plasma. METHODS: The Galileo automatic blood analyzer was used to detect the titers of IgM anti-A and anti-B antibodies in the samples of group O blood donors and IgM anti-B titer in the samples of group A blood donors. Group O blood donors with antibody titers below 128 were selected and included in the mobile blood bank for combat readiness, group A plasma with anti-B titer lower than 128 and group O whole blood with antibody titers below 128 were included in the combat readiness entity blood bank. RESULTS: A total of 1 452 group O blood donors were selected, and the anti-A/B antibody titers were detected. Both antibody titers were distributed below 512, and both peak values of sample distribution were at titer 4. The proportion of samples with titers>128 for both antibodies was relatively low. There was a significant positive correlation between the titers of the two antibodies (r =0.383), and the proportion of samples with IgM anti-A titer higher than IgM anti-B titer was relatively high. 1 335(91.94%) group O blood donors with IgM anti-A and anti-B antibody titers <128 could be included in the mobile blood bank. The anti-B titer of group A blood was detected in 512 cases and the results showed that as the antibody titer increased, the proportion of blood donors gradually decreased. 99.8% of group A blood donors had anti-B antibody titer less than 128, and only one case did not meet the inclusion criteria. CONCLUSION: The proportion of group O blood donors whose whole blood meet the low antibody titer standard is high, and almost all plasma of group A blood donors meet the low titer standard, which improves the blood supply rate in emergencies.

Blood groups and Rhesus status as potential predictors of outcomes in patients with cardiac resynchronisation therapy.

Cardiac resynchronisation therapy (CRT) improves prognosis in patients with heart failure (HF) however the role of ABO blood groups and Rhesus factor are poorly understood. We hypothesise that blood groups may influence clinical and survival outcomes in HF patients undergoing CRT. A total of 499 patients with HF who fulfilled the criteria for CRT implantation were included. Primary outcome of all-cause mortality and/or heart transplant/left ventricular assist device was assessed over a median follow-up of 4.6 years (IQR 2.3-7.5). Online repositories were searched to provide biological context to the identified associations. Patients were divided into blood (O, A, B, and AB) and Rhesus factor (Rh-positive and Rh-negative) groups. Mean patient age was 66.4 ± 12.8 years with a left ventricular ejection fraction of 29 ± 11%. There were no baseline differences in age, gender, and cardioprotective medication. In a Cox proportional hazard multivariate model, only Rh-negative blood group was associated with a significant survival benefit (HR 0.68 [0.47-0.98], p = 0.040). No association was observed for the ABO blood group (HR 0.97 [0.76-1.23], p = 0.778). No significant interaction was observed with prevention, disease aetiology, and presence of defibrillator. Rhesus-related genes were associated with erythrocyte and platelet function, and cholesterol and glycated haemoglobin levels. Four drugs under development targeting RHD were identified (Rozrolimupab, Roledumab, Atorolimumab, and Morolimumab). Rhesus blood type was associated with better survival in HF patients with CRT. Further research into Rhesus-associated pathways and related drugs, namely whether there is a cardiac signal, is required.

N-glycoproteomic analyses of human intestinal enteroids, varying in histo-blood group geno- and phenotypes, reveal a wide repertoire of fucosylated glycoproteins.

Human noroviruses, globally the main cause of viral gastroenteritis, show strain specific affinity for histo-blood group antigens (HBGA) and can successfully be propagated ex vivo in human intestinal enteroids (HIEs). HIEs established from jejunal stem cells of individuals with different ABO, Lewis and secretor geno- and phenotypes, show varying susceptibility to such infections. Using bottom-up glycoproteomic approaches we have defined and compared the N-linked glycans of glycoproteins of seven jejunal HIEs. Membrane proteins were extracted, trypsin digested, and glycopeptides enriched by hydrophilic interaction liquid chromatography and analyzed by nanoLC-MS/MS. The Byonic software was used for glycopeptide identification followed by hands-on verifications and interpretations. Glycan structures and attachment sites were identified from MS2 spectra obtained by higher-energy collision dissociation through analysis of diagnostic saccharide oxonium ions (B-ions), stepwise glycosidic fragmentation of the glycans (Y-ions), and peptide sequence ions (b- and y-ions). Altogether 694 unique glycopeptides from 93 glycoproteins were identified. The N-glycans encompassed pauci- and oligomannose, hybrid- and complex-type structures. Notably, polyfucosylated HBGA-containing glycopeptides of the four glycoproteins tetraspanin-8, carcinoembryonic antigen-related cell adhesion molecule 5, sucrose-isomaltase and aminopeptidase N were especially prominent and were characterized in detail and related to donor ABO, Lewis and secretor types of each HIE. Virtually no sialylated N-glycans were identified for these glycoproteins suggesting that terminal sialylation was infrequent compared to fucosylation and HBGA biosynthesis. This approach gives unique site-specific information on the structural complexity of N-linked glycans of glycoproteins of human HIEs and provides a platform for future studies on the role of host glycoproteins in gastrointestinal infectious diseases.

[Genetic analysis of two patients with a rare Ael subtype].

OBJECTIVE: To analyze the genetic sequences of two patients with a rare Ael blood subgroup. METHODS: Two female patients undergoing treatment respectively for adenomyoma of the uterus and gastritis at the Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University in June 2019 and September 2020 were selected as the study subjects. Their Ael subtypes were identified with a saline tube agglutination assay and absorption-emission assay. Sequence of the ABO gene Ael subtypes was determined by the Sanger method. The impact of genetic variants on the structural stability of N-acetylgalactosaminyl transferase (GTA) was analyzed with PyMOL software by constructing a structure predicted model. RESULTS: Both patients were determined as Ael blood subgroup. Sequencing result of patient 1 was ABO*O.01.02/ABO*O.01.02, which has resulted in a p.Thr88Profs*31 amino acid substitution. The sequencing result of patient 2 was ABO*Ael.06/ABO*O.01.02, in which c.425C>T and c.467C>T variants in exon 7 have led to p.Met142Thr and p.Pro156Leu substitutions. Prediction of the protein model speculated that the p.Met142Thr not only can change the binding of GTA protein with water molecules, but also the local hydrogen bond network of GTA, which may lead to decreased enzymatic activity. By contrast, the p.Pro156Leu variant has trivial effect on the structural stability of GTA. CONCLUSION: The molecular structure of Ael subtypes can be diverse. The genotypes of the two patients have been respectively determined as ABO*O.01.02/ABO*O.01.02 with a G261 deletion and ABO*Ael.06/ABO*O.01.02.

[Molecular study of an individual with Bel subtype due to a novel c.620T>C variant].

OBJECTIVE: To explore the molecular basis for an individual with Bel subtype of the ABO blood type due to a novel c.620T>C variant gene, and assess its impact on the structure of GTB transferase. METHODS: An individual who had visited the First Affiliated Hospital of Zhengzhou University on February 11, 2023 was selected as the study subject. ABO phenotyping was initially conducted with serological methods, which was followed by direct sequencing of 7 exons of the ABO gene. Subsequently, single-strand sequencing was carried out by using allele-specific primers, and the variant in the B transferase was homology-modeled using the Modeller software. The impact of the variant on the transferase's spatial structure was analyzed with the PyMOL software. RESULTS: The serological phenotype of the patient was identified as the Bel subtype. Direct sequencing revealed that she has harbored a novel c.620T>C variant, resulting in a p.Leu207Pro substitution in the polypeptide chain. Combined with single-strand sequencing, her genotype was ultimately determined as ABO*BELnew/ABO*O.01.02. Three-dimensional protein structure modeling showed that, compared with the wild type, the distance of one hydrogen bond between Proline and Glycine at position 272 has increased, along with disappearance of another hydrogen bond. CONCLUSION: The novel c.620T>C (p.Leu207Pro) variant of B allele may affect the structural stability of the glycosyltransferase. The weakened enzyme activity in turn may lead to reduced B antigen expression, manifesting as the Bel subtype by serological analysis.

Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood.

Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics and prevent ABO-mismatched transfusions. The gut symbiont Akkermansia muciniphila can degrade mucin O-glycans including ABO epitopes. Here we biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions. Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analyses of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module. This study demonstrates the potential utility of mucin-degrading gut bacteria as valuable sources of enzymes for production of universal blood for transfusions.

Blood count changes in malaria patients according to blood groups (ABO/Rh) and sickle cell trait.

INTRODUCTION: Introduction: Malaria continues to be the leading cause of hospitalization and death in Angola, a country in sub- Saharan Africa. In 2023, in the first quarter, 2,744,682 cases were registered, and of these 2,673 patients died due to malaria disease. Previous studies have shown that the ABO blood group can affect the progression of malaria to severe conditions after P. falciparum infection, while the sickle cell gene offers relative protection. OBJECTIVE: We investigated changes in the blood count according to blood groups (ABO/Rh) and sickle cell trait in patients with malaria in Luanda, capital of Angola. METHODOLOGY: This was a longitudinal, prospective and observational study with 198 patients hospitalized for malaria. RESULTS: Of the 198 patients studied, 13(6.6%) were ABRh(+), 4(2.0%) were ARh(-), 49(24.7%) were ARh(+), 42(21, 2%) were BRh (+), 5(2.5%) were ORh(-) and 85(42.9%) were ORh(+). For sickle cell trait, 145(73.2%) were AA, 37(18.7%) were AS and 16(8.1%) were SS. No statistical relationship was observed between age group, sex, parasitemia, clinical picture, hematocrit, MCV, HCM, MCHC, leukocytes, NEUT, LINF and PTL values with blood groups (p<0.05), but there was a relationship between values of hemoglobin and ABO/Rh blood groups (p>0.05). There was no relationship between age, parasitemia, clinical condition, MCV, HCM and MCHC values, leukocytes, NEUT and LINF with sickle cell trait (p<0.05), but there was a relationship between sex, hemoglobin and PTL and sickle cell values. sickle cell trait (p>0.05). CONCLUSION: It is imperative to differentiate patients with malaria based on blood groups and sickle cell trait, taking into account mainly the blood count parameters that demonstrate that there are patients who, depending on blood group or sickle cell trait, may react weakly to malaria infection regardless of the degree of parasitemia and medical prognosis.

Consideration for alpha-gal syndrome in two critically ill persons with group O blood who received group B plasma.

BACKGROUND: The U.S. Centers for Disease Control and Prevention (CDC) has reported increasing rates of alpha-gal syndrome, an allergic response after meat ingestion (AGS). AGS has been associated with prior exposure to tick bites or other biologics characterized by a life-threatening immunoglobulin E (IgE)-mediated hypersensitivity to galactose-alpha-1,3-galactose (alpha-gal) an oligosaccharide structurally similar to the group B antigen on red blood cells (RBC) found in most non-primate mammalian meat and products derived from these mammals. In 2023, Transfusion reported 3 group O recipients of group B plasma in the Washington, D.C. metropolitan area with no history of meat allergy who had anaphylactic transfusion reactions compatible with AGS. AIMS: We investigated allergic reactions in 2 additional patients who received ABO minor-incompatible blood products at 2 hospitals in the D.C. area during fall 2023. METHODS: For both patients, a medical chart review was performed and IgE levels to alpha-gal were measured. RESULTS: The first patient, a 64-year-old, O-positive patient status post heart transplant with no known allergies, was admitted with acute COVID-19 induced antibody-mediated transplant rejection and placed on extracorporeal membrane oxygenation (ECMO). While undergoing plasma exchange (PLEX) (50% albumin/50% fresh frozen plasma (FFP)), the patient tolerated 2 units of group O FFP and 1 unit of group A FFP before becoming hemodynamically unstable during transfusion of 1 unit of B-positive FFP. PLEX was stopped. The patient later died of sepsis from underlying causes. The second patient, a 57-year-old O-positive man with a history of melanoma and neuro fibromatosis type 1, was undergoing an abdominal resection including transfusion of 3 units of O-positive RBC when he suffered hypotension and ventricular tachycardia requiring intraoperative code after receiving 2 units of group B FFP. Hiveswere noted after resuscitation. The patient had a history of tick bites but no known allergies. He is alive 5 months after the possible allergic event. Both patients had full transfusion reaction evaluations and immunology testing results above the positive cutoff for anti-alpha-gal IgE. DISCUSSION AND CONCLUSION: Two patients with O-positive blood and no known allergies experience danaphyl axis after transfusion with group B FFP. The symptoms cannot definitively be imputed to an allergic transfusion reaction, but the presence of IgE against alpha-gal supports an association. Medicating patients with antihistamines and IV steroids pre-transfusion may prevent allergic reactions. Restricting group B plasma-containing products (plasma, platelets, cryoprecipitate) for patients who experience AGS-like symptoms may be considered.

Impact of ABO blood group on mortality in trauma patients: A systematic review.

BACKGROUND: Haemorrhage is a significant cause of death in trauma patients. There is evidence that individuals with blood group O have higher rates of non-traumatic haemorrhage. It has been suggested that blood group O may be associated with higher mortality in trauma, however existing evidence is limited and conflicting. OBJECTIVE: A systematic review was conducted to evaluate the impact of ABO blood group on mortality in trauma patients. METHODS: MEDLINE via OVID, the Cochrane library and grey literature were searched to identify studies investigating the effect of ABO blood group on mortality of trauma patients admitted to hospital. PRISMA guidelines were followed throughout, study quality was assessed using CASP checklists and certainty of evidence was evaluated using GRADE. Meta-analysis was precluded by significant study heterogeneity. RESULTS: 180 relevant records were screened and seven studies met inclusion criteria, representing 12,240 patients. Two studies found that there was a higher mortality in blood group O compared to other ABO groups. Included studies had substantial variability in methods and population. Study quality was variable with certainty of evidence rated as very low. CONCLUSIONS: There is insufficient evidence to definitively establish an association between mortality and ABO group in trauma patients. In an age of increasingly individualised care, there is a need to determine the existence and cause for any association through further studies across multiple settings, trauma mechanisms and populations.