ABO Blood Group Incompatibility Protects Against SARS-CoV-2 Transmission

ABO blood groups appear to be associated with the risk of SARS-CoV-2 infection, but the underlying mechanisms and their real importance remain unclear. Two hypotheses have been proposed: ABO compatibility-dependence (neutralization by anti-ABO antibodies) and ABO-dependent intrinsic susceptibility (spike protein attachment to histo-blood group glycans). We tested the first hypothesis through an anonymous questionnaire addressed to hospital staff members. We estimated symptomatic secondary attack rates (SAR) for 333 index cases according to spouse ABO blood group compatibility. Incompatibility was associated with a lower SAR (28% vs. 47%; OR 0.43, 95% CI 0.27–0.69), but no ABO dependence was detected in compatible situations. For the second hypothesis, we detected no binding of recombinant SARS-CoV-2 RBD to blood group-containing glycans. Thus, although no intrinsic differences in susceptibility according to ABO blood type were detected, ABO incompatibility strongly decreased the risk of COVID-19 transmission, suggesting that anti-ABO antibodies contribute to virus neutralization.

Post-Hematopoietic Stem Cell Transplantation Immune-Mediated Anemia: A Literature Review and Novel Therapeutics

Anemia following allogeneic hematopoietic stem cell transplantation (HCT) can be immune- or non-immune mediated. Auto- or alloimmunity due to blood groups incompatibility remain an important cause if post-HCT immune-mediated anemia. ABO incompatibility is commonly encountered in HCT and may lead to serious clinical complications including acute hemolysis, pure red cell aplasia, and passenger lymphocyte syndrome. It remains controversial whether ABO incompatibility may affect HCT outcomes, such as relapse, non-relapse mortality, graft-versus-host disease and survival. Non-ABO incompatibility is less frequently encounterd but can have similar complications to ABO incompatibility, causing adverse clinical outcomes. It is crucial to identify the driving etiology of post-HCT anemia in order to prevent and treat this condition. This requires a comprehensive understanding of the mechanism of anemia in blood group incompatible HCT, and the temporal association between HCT and anemia. In this review, we summarized the literature on post-HCT immune-mediated anemia with a focus on ABO and non-ABO blood group incompatibility, described the underlying mechanism of anemia, and outlined preventive and treatment approaches.

Cord Bilirubin Value as a Predictor of Significant Hyperbilirubinemia in Abo Incompatiblity

Background: Hyperbilirubinemia is a condition in which the blood contains too much bilirubin and producing jaundice (yellow coloring of the eyes and skin). Low bilirubin levels in newborns are common and do not pose any problems; they will resolve on their own within the first week of life. Studying the cord bilirubin levels in new born babies is significant to predict the risk of abo incompatiblity. Methods: A total of 129 babies born to O blood group mother were included in the study. Out of which 111 babies were with risk of ABO incompatibility. Among them 17 babies developed pathological hyperbilirubinemia. None of the 0 positive babies developed pathological hyperbilirubinemia. Results: The peak bilirubin level was attained on 3rd and 4th day for all the babies and was taken as the outcome measure and cord serum bilirubin was taken as the predictive factor. The incidence of pathological hyperbilirubinemia is 13.2%. The mode of delivery had no positive association with the development of pathological hyperbilirubinemia. Male babies had positive ociation for pathological hyperbilirubinemia without any statistical significance. Incidence of pathological hyperbilirubinemia is higher in babies with a birth weight of <3 kg. Conclusion: A cord bilirubin value of 2.65 mg/dL can be used as a cut off for predicting pathological hyperbilirubinemia. Infants with bilirubin level more than the cutoff values were subjected to early intervention with complete recovery. None of the babies had developed encephalopathy and its sequelae.

Risk Due to ABO Incompatibility and Donor-Recipient Weight Mismatch in Living Donor Kidney Transplantation: A National Cohort Study

The effect of donor-recipient weight mismatch is not well established in ABO-incompatible living donor kidney transplantation (LDKT). A total of 2584 LDKT patients in the Korean Organ Transplantation Registry were classified into four groups according to the presence or absence of ABO incompatibility and donor-recipient weight mismatch (donor-to-recipient weight ratio (DRWR) < 0.8). In a multivariable Cox analysis, the combination of ABO incompatibility and DRWR incompatibility (n = 124) was an independent risk factor for graft survival (HR = 2.73, 95% CI = 1.11–6.70) and patient survival (HR = 3.55, 95% CI = 1.39–9.04), whereas neither factor alone was a significant risk factor for either outcome. The combination of ABO incompatibility and DRWR incompatibility was not an independent risk factor for biopsy-proven graft rejection (HR = 1.27, 95% CI = 0.88–1.82); however, it was an independent risk factor for pneumonia (HR = 2.94, 95% CI = 1.64–5.57). The mortality rate due to infection was higher among patients with both ABO incompatibility and DRWR incompatibility than among patients with neither factor or with either factor alone. The combination of ABO incompatibility and DRWR incompatibility was an independent risk factor for graft and patient survival after LDKT, whereas neither factor alone significantly affected graft or patient survival. Thus, donor-recipient weight matching should be cautiously considered in LDKT with ABO incompatibility.

Positive direct antiglobulin test: is it a risk factor for significant hyperbilirubinemia in neonates with ABO incompatibility?

Objective: ABO incompatibility is a common cause of neonatal indirect hyperbilirubinemia. The direct antiglobulin test (DAT) can identify infants developing hemolytic disease. This study aims to evaluate the significance of DAT positivity among neonates with ABO incompatibility. Study Design: This retrospective study included 820 neonates with blood group A or B who were born to blood group O mothers. The study group consisted of neonates (n = 79) who had positive DAT, and the control group consisted of infants (n = 741) who had negative DAT. Demographic and clinical data of the neonates regarding jaundice were collected and compared statistically. Results: The bilirubin level at 24 hours of life (study group 8 ± 2.6 mg/dl, control group 6 ± 2.2 mg/dl, p < 0.001) and the highest bilirubin level (study group 12.7 ± 3.6 mg/dl, control group 10.4 ± 4.2 mg/dl, p < 0.001) were higher in infants with positive DAT. In the study group 37 (46.8%) infants and in the control group 83 (11.2%) infants received PT in the nursery (p < 0.001). In neonates with positive DAT; direct bilirubin level, duration of hospitalization, and PT in the nursery were higher (p = 0.002, p < 0.001, and p < 0.001), whereas hemoglobin level was lower (p < 0.001). Conclusion: In neonates with ABO incompatibility, a positive DAT is a risk factor for developing significant hyperbilirubinemia. Close follow-up of newborn infants with ABO incompatibility is crucial for early detection and treatment of neonatal jaundice to avoid early and late complications.

Study of discrepancies in ABO blood grouping: experience of a tertiary health-care center

Background: An accurate ABO grouping is the most important test which is done in the blood bank. Mistyping can lead to transfusion with ABO incompatible blood which results in severe intravascular haemolysis and may even result in the death of the recipient. An ABO discrepancy implies that the forward or red cell ABO grouping does not agree with the reverse or serum ABO grouping. The study was conducted to evaluate the frequency of ABO blood group discrepancies, to identified main causes of discrepancies, to avoid chances of wrong interpretation of blood group and to mitigate clinical impact associated with mismatch ABO transfusion.Methods: A prospective study of ABO discrepancies and their causes was performed on 25,129 samples of the patients and 13,251 samples of blood donors at the red cell serology laboratory in tertiary care teaching hospital and blood bank over the period from February 2017 to July 2018.Results: ABO group discrepancies were mainly divided in 4 different groups. Out of 51 discrepancies 32 (62.74%) were found in group-IV category, being highest amongst all; 10 (19.60%) in group-II which was second highest; other were 8 (15.69%) in group-I and 1 (1.96%) in group-III category.Conclusions: All discrepancies reported on ABO cell and serum grouping must be investigated further, so that correct blood group is reported, minimizing the chances of transfusion reaction. A note of caution should be mentioned on the blood group card to prevent ABO incompatibility in case of transfusion.

Clinical profile of pathological Jaundice among neonates admitted in the National Referral Hospital, Bhutan

Background: Neonatal jaundice is a common condition especially in the first week of life. There are various maternal and neonatal clinical characteristics that have been associated with pathological jaundice. Objectives: To describe clinical profile of pathological jaundice and to estimate its prevalence among newborns admitted at the National Referral Hospital. Methods: A cross-sectional descriptive study design was used to study pathological jaundice cases admitted at the Gyaltsuen Jetsun Pema Neonatal Intensive Care Unit (NICU) of Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) from 7th November 2018 till 6th November 2019. Data was collected using a predesigned case proforma, entered and analyzed in Epidata after obtaining ethical clearance from the Research Ethics Board of Health (REBH), Bhutan. Results: Facility based prevalence rate of pathological neonatal jaundice was found to be 63.66% in our setting. The median age on presentation was 4 days. Blood group ABO incompatibility and neonates less than one week of age were found to be most common neonatal profile in this study. Significant association was found between primiparous mothers and excessive weight loss. Conclusion: The prevalence of pathological jaundice was high in our setting. ABO incompatibility, neonates less than one week of age, primigravida mothers with feeding issues should be closely followed or screened for pathological jaundice especially during the first one week of life. Keywords: Pathological jaundice, Prevalence, ABO incompatibility, feeding issues, excessive weight loss

Severe Hemolytic Disease of Newborn Due to Alloimmune Anti-E Antibodies: A Case Report

Hemolytic disease in the newborn (HDN) as a cause of early jaundice is mostly due to Rh (D), ABO incompatibility, and rarely due to other minor blood group incompatibility. We report case of Rh anti-E isoimmunization presenting as significant unconjugated jaundice within the 24 h of life. Baby presented with severe jaundice and anemia on day 1 of life. Baby was treated with intensive phototherapy, double volume exchange transfusion (DVET), and intravenous immunoglobulins. On evaluation, both mother and baby had O positive (Rh) blood group; however, the infant showed evidence of severe hemolysis. Positive direct Coombs test (DCT) and 11 cell antibody panel showed anti-E antibodies. This case highlights the importance of early identification and evaluation of HDN in the absence of Rh(D) and ABO incompatibility and possibility of severe hemolysis in Rh anti-E isoimmunization needing DVET.

Incidence and Risk Factors Associated with Fatal Graft Vs Host Disease after Solid Organ Transplantation in United Network of Organ Transplant Database

INTRODUCTION Graft vs host disease (GVHD) is a rare complication after solid organ transplantation ( ̴ 1-2% with liver and ̴ 5.6% with intestines), but is associated with high mortality (70-80%). In contrast to GVHD following hemopoietic stem cell transplant, bone marrow infiltration by donor T lymphocytes leading to cytopenia ( ̴ 80%) is a common manifestation of GVHD after solid organ transplantation (Murali et. al., 100(12), Transplantation, January 2016). The risk factors associated with GVHD occurring after solid organ transplantation have not been well characterized, but single institution studies have suggested donor/recipient (D/R) HLA mismatch, ABO incompatibility and gender mismatch playing important roles. However, some studies have identified that similarities in HLA type which permit mismatches unrecognized by the recipient as a common mechanism preventing rejection of donor lymphocytes, which then can cause GVHD in the recipient. In order to evaluate potential risk factors, we reviewed the transplant data of patients in whom GVHD was listed as the cause of death from United Network of Organ transplant database (UNOS), the database that contains all US organ transplant data. METHODS From the UNOS database we obtained information of patients that underwent liver or intestinal transplantation between 1987-2020 in the US. The patients for whom GVHD was reported as the cause of death were identified. Baseline D/R and transplant variables were collected. Patient or transplant related characteristics were presented via descriptive statistics. Corresponding P-values were determined using Chi-square test for categorical variables and two-sample t-test for continuous variables. The incidence of mortality caused by GVHD was estimated using the cumulative incidence method, accounting for non-GVHD related death as a competing risk. All statistical tests were two sided, and a P-value &lt; 0.05 was considered significant. RESULTS Of a total of 179,355 patients that underwent liver transplantation, 216 (0.1%) patients had GVHD identified as the primary cause of death (GVHD group). The HLA mismatch information was available in 86,434 patients (48.2%). HLA mismatch was grouped into low level (0-3) and high level (4-6). Low level HLA mismatch was 24.6% in the GVHD group compared to 16.2% in patients that are alive or died of non-GVHD related causes (non-GVHD group). High level mismatch was 75.4% in GVHD group and 83.8% in the non-GVHD group (P=0.013). Other risk factors including gender mismatch (40.3% vs 42.5%, P=0.536), ABO incompatibility between D/R (0.5% vs 1.4%, P=0.42) and use of live donors (1.9% vs 4.3%, p= 0.09) were similar between the two groups. Patients in the GVHD group were older with median age of recipient being 59 years compared to 53 years in the non-GVHD (P&lt;0.001). Graft failure was more common in the GVHD group compared to non-GVHD group (33.8% vs 17.1%, P&lt;0.001). Of a total of 3,153 patients that underwent intestinal transplantation, 20 (0.6%) patients had GVHD identified as the primary cause of death (GVHD group). The HLA mismatch information was available in 2859 patients (90.6%).The high-level HLA mismatch (83.3% vs 84.7%, P=0.749), gender mismatch (40% vs 47.1%, P=0.655) and ABO incompatibility (0% vs 0.2%, P=0.757) between D/R were similar between the GVHD group and non-GVHD group among intestinal transplant patients. Conclusions In patients that undergo hematopoietic stem cell transplant, HLA and gender mismatch between D/R have been recognized as risk factors for GVHD. Based on the largest analysis of solid organ transplant database, traditionally considered GVHD risk factors like HLA and gender mismatch between D/R do not appear to be significantly associated with severe GVHD leading to death. Recipient age and graft failure are significantly associated with GVHD related deaths in liver transplant patients. These findings suggest that other risk factors for severe GVHD leading to death after solid organ transplant than those previously reported in single institution studies should be examined and underscore the need for additional studies. Figure 1 Figure 1. Disclosures Grunwald: Med Learning Group: Other; Agios: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Janssen: Research Funding; Amgen: Consultancy; Pfizer: Consultancy; PRIME: Other; PER: Other; Karius: Consultancy; Sierra Oncology: Consultancy; Blueprint Medicines: Consultancy; Incyte: Consultancy, Research Funding; AbbVie: Consultancy; Bristol Myers Squibb: Consultancy; Stemline: Consultancy; Gilead: Consultancy; Cardinal Health: Consultancy; Trovagene: Consultancy; MDEdge: Other. Copelan: Amgen: Consultancy.