Bombay Phenotype Research Articles

A rare blood group (Bombay blood group)

The subsistence of a human H/h genetic polymorphism was first recognized by the innovation of an individual devoid of the H antigen on red cells in Bombay who had antibodies in plasma reacting with all the red cells exhibiting the normal red cell ABO phenotypes. These persons were genetically termed as homozygous hh or Bombay phenotype. H-deficient Bombay phenotype is exceptional, since it occurs in about 1 in 10,000 individuals in India and 1 per 1,000,000 individuals in Europe. After the first report of Oh phenotype from Mumbai in 1952 by Bhende, numerous other workers detected this weird phenotype in India. The complexity with the Bombay phenotype is that the individuals having blood group of Bombay phenotype (Oh) can either receive autologous donation or blood from an individual of Bombay phenotype only; no other blood will match in case of an emergency blood transfusion. The aim of present study was to communicate the information about rare blood entity and to review the previous case reports.

An update on the H blood group system

This update of the H blood group system (Scharberg EA, Olsen C, Bugert P. The H blood group system. Immunohematology 2016;32:112-8) reports 11 new FUT1 null alleles: 8 causative for the H- phenotype (Bombay phenotype, Oh), 3 in para-Bombay cases, and 5 new FUT1 alleles causative for a weak H phenotype (para-Bombay, H+w). The H blood group system (International Society of Blood Transfusion system 18) consists of a single antigen (H) defined by a terminal fucose residue found on red blood cells (RBCs) and in secretions. The H antigen is synthesized on the RBC surface by the FUT1 gene product fucosyltransferase 1. On epithelial cells and in body fluids, the H antigen is synthesized by the FUT2 gene product fucosyltransferase 2.

The First Comprehensive Study of H-Deficient Phenotypes in Iran

Summary Background: The lack of correct blood grouping practices can lead to missing of the rare Bombay Oh phenotype and subjecting patients to the risk of severe hemolytic transfusion reaction. In the absence of blood donor registry, transfusion management of patients is a challenge. We performed this study in order to estimate the prevalence of the Bombay blood group (Oh) in Iran and to determine whether consanguinity plays a role in the prevalence of Oh group. Methods: This is a descriptive study in the Immunohematology Reference Laboratory of the Iranian Blood Transfusion Organization (IBTO) Tehran, Iran, over a period of 7 years. All donor blood samples showing blood group O and a strong initial reaction with blood group O RBC control cells were tested with anti-H lectin. Also blood samples from blood group O patients were tested with anti-H lectin if all cells on both antibody screening tests and antibody identification panels were reactive with negative auto control test. Specialized tests like adsorption/elution technique and inhibition assay for determination of secretor status were performed on Oh cases. Any history of consanguineous marriages were recorded. All variables were categorical variables, and percentage and proportions were calculated manually. Results: Analysis of the results of over 7 million first-time blood donors in Iran showed that the most common ABO blood group was O, with 2,520,000 (36%) subjects. 56 Oh individuals' (donors and patients) phenotypes (0.0008%) were detected. Consanguinity was observed in 50 cases (89%). Conclusions: This study shows that the prevalence of Bombay blood group in the general population of Iran is relatively high (0.0008%) and associated with consanguineous marriage. Thus, consanguinity is still an important risk factor present.

Mutational Analysis of Bombay Phenotype in Iranian People: Identification of a Novel FUT1 Allele.

Bombay phenotype is characterized by lack of ABH antigens on RBCs and in body secretions as a result of mutations in fucosyltransferase 1 (FUT1) and fucosyltransferase 2 (FUT2) genes. The aim of this study was a mutational analysis in Iranians with this phenotype. Serological analyses including ABH and adsorption-elution tests were performed in five unrelated Bombay individuals. ABO genotyping was determined by direct sequencing. The coding regions of FUT1 and FUT2 genes were amplified and sequenced directly or after cloning into suitable vector. A novel missense FUT1 allele was detected (G1051T; G351C). Also four reported FUT1 alleles were revealed. Molecular analysis of FUT2 gene confirmed nonsecretor status in all individuals. This and our previous findings suggest the diversity and population specificity of FUT1 alleles.

Bombay phenotype (Oh) and high‐titer anti‐H in pregnancy: two case reports and a review of the literature

Antenatal cases of Bombay-phenotype (Oh ) individuals and hemolytic disease of the fetus and newborn (HDFN) are not well described in the literature. We present two case reports of high-titer anti-H in pregnant Oh individuals and their serologic investigation, clinical management, and subsequent outcomes. We describe current published cases detailing pregnancy in Oh individuals, to add to the evidence base for clinical decision making and management of pregnancy. We describe two case reports of high-titer anti-H in pregnancy in Oh individuals. We summarize published cases to date, to inform clinical decision making and antenatal management in individuals with the Bombay phenotype. Of the case reports described, neither were affected by HDFN due to anti-H. Antibody titers were high in both cases (immunoglobulin G titer scores, 512 and 4000, respectively) and would be expected to cause some degree of HDFN, a surprising finding. Regular mean cerebral artery Doppler ultrasound was normal. Patient blood management (PBM) techniques ensured that the patient's hemoglobin (Hb) levels were monitored and maintained. Transfusion intervention was not required, with minimal blood loss recorded at birth in both cases. High-titer anti-H in Oh pregnancies may, in rare cases, cause HDFN, but evidence suggests that this may not be the case in all pregnancies. We recommend a multidisciplinary approach, with prompt referral to a fetomaternal medicine unit, combined with PBM strategies, and a planned delivery with the provision of rare-phenotype units (if available and if indicated) on standby.

Blood Transfusion Challenge to Anaesthesiologist – A Case of Bombay Blood Group

Blood Transfusion Challenge to Anaesthesiologist – A Case of Bombay Blood Group

Retrospective analysis of forward and reverse ABO typing discrepancies among patients and blood donors in a tertiary care hospital.

The aim of our study was to determine the incidence and causes of ABO typing discrepancies among patients and blood donors at our centre. An accurate interpretation of the ABO blood group of an individual is of utmost importance to ensure patient safety and good transfusion practices. A retrospective observational study was carried out in the Department of Transfusion Medicine in our hospital from March 2013 to December 2015. Records of all patient and blood donor samples were retrieved and analysed for ABO typing discrepancies. In total, 135 853 patient and 62 080 donor samples were analysed for ABO typing discrepancies. The incidence among patients and blood donors was found to be 0·1% (138/135853) and 0·02% (14/62080), respectively. The mean age for patients and blood donors was 48·4 and 29·2years, respectively. The most common cause of ABO typing discrepancies was due to cold autoantibodies among the patients (50·7%) and blood donors (57%) causing discrepant results in reverse typing. The various other causes of reverse typing discrepancies among patients were weak/missing antibody (25·4%), cold-reacting alloantibody (4·3%), warm autoantibody (2·2%), anti-A1 antibody (2·2%), Bombay phenotype (1·5%), transplantation (0·7%) and rouleaux (0·7%), whereas in blood donors, the causes were cold-reacting antibody (7%) and weak antibody (7%). The major cause of forward typing discrepancies among patients (12·3%) and blood donors (29%) was ABO subgroups. The resolution of ABO typing discrepancy is essential to minimise the chance of transfusion of ABO-incompatible blood.

A Very Rare Case with Particular H-deficient Phenotypes.

Bombay phenotype, H partially deficient non secretor phenotype and Para-Bombay phenotype are rare blood groups with deficiency or absence of H antigen. A 52-year-old female with Chronic suppurative otitis media was referred to our hospital. The primary serologic results of ABO blood typing were discrepant in forward and reverse grouping. Further, the saliva secretion tests, the pedigree studies and the sequence analysis were performed to confirm the rare phenotype. The patient was diagnosed as a variant H-deficient phenotype, secretor (para-bombay). Red cells of the patient have no H antigens, and it's a very interesting thing that there were two opposite results in the saliva test by using different anti-H. The test showed that H substances were present in the saliva by using anti-H from Libo Biotechnology Co, while which were absent by using anti-H from Shanghai blood center. The patient's Lewis phenotype was Le (a-b+). Anti-HI was present in the sera of her. The sequence of the ABO gene of the patient was 261delG and 467C>T heterozygote by direct DNA sequencing and was assigned as A102/O01. There were two mutations of the patient's FUT1, 328G/A and 658C/T, which were identified by DNA sequencing compared with the reference sequence (GenBank, NG_007510.2). In this case, we report a patient with particular H-deficient phenotype, secretor, which showed opposite results in the saliva test by using anti-H from different sources. We suspect that it is a variant of para-Bombay phenotype.

First Case of Renal Transplantation Involving a Donor with Bombay Phenotype Blood Group.

First Case of Renal Transplantation Involving a Donor with Bombay Phenotype Blood Group.

Incompatible Crossmatch with Bombay Phenotype (Oh) - A Case Report

Blood serology plays a vital role in transfusion medicine. Presence of an irregular antibody (anti H) in the plasma reacting with all the red cells exhibiting the normal red cell ABO phenotype, the h/h (Bombay) phenotype. The h/h phenotype also known as Oh or Bombay blood group is a rare blood type. It was first discovered in Bombay (Mumbai) in India by Dr.Y.G. Bhende et al in 19521 Generally present in about 4 per million of the human population, though in some places such as Mumbai (Bombay) locals can have occurrences in as much as 1 in 10,000 of inhabitants2 It is also very rare in Bangladesh. The first case was reported in 1990 where three sisters in a same family were of 'Bombay' phenotype3. A 28-year-old male of Noakhali district was admitted to Apollo Hospitals Dhaka on 21st may 2016 with road traffic accident with pelvic fracture. His ABC and Rh blood group was detected as 0 positive by usual blood grouping test procedure. But his cross match was incompatible with several 0 positive blood units. Though the patient’s blood group phenotype initially mimic normal group 0 type by usual test procedure but became apparent when his serum was tested against group 0 red cells and strong Mediate spin agglutination developed at a thermal range 4° to 37°C. After testing with anti H Lectin, Ulex europaeus having anti H like activity, it was detected as Bombay blood group. Therefore, proper serum grouping using A cell, B cell and 0 cell is necessary to detect this group. Bombay phenotype individual do not express H, A and B antigen on their red cells and secretions but their plasma contains potent anti H, anti A and anti B due to lack H antigen4 Normal 0 group red cells does not have A or B antigen but their membrane expresses abundant H antigen. Anti H of Bombay phenotype serum gives incompatible cross match with all red blood cells of normal ABO phenotype containing H antigen. oh phenotype person can receive only autologous blood or blood from another Bombay blood group donor.5 This patient has received blood from her own sister who was also Bombay phenotype but his other four brothers were normal 0 group. Later on he was transfused with blood from Bombay blood group donor, arranged from “Think Foundation”, Mumbai, India for his orthopedic surgery. Both forward and reverse grouping is important for safe transfusion. If not followed, it may lead to people with Bombay blood group, not being detected and categorized as 0 group. Therefore, proper reverse grouping is necessary to detect this group and cross matching at different thermal range also plays a vital role in transfusion safety.Pulse Vol.9 January-December 2016 p.54-59

Design of Artificial Glycosidases: Metallopeptides that Remove H Antigen from Human Erythrocytes

AbstractCatalysts that promote carbohydrate degradation have a wide range of potential applications, but the use of either enzyme glycosidases or small‐molecule catalysts in biological systems raises significant challenges. Herein, we demonstrate a novel strategy for the design of synthetic agents that mimic natural glycosidases and address current problems for biological use. This strategy is illustrated by application to the development of potential blood substitutes for the rare Bombay blood type that is characterized by a deficiency of H2 antigen. Metallopeptides with 16 to 20 amino acids were constructed as artificial fucosidases that exhibit selective carbohydrate cleavage reactivity toward l‐fucose over d‐glucose. Selective fucose cleavage from the H2‐antigen saccharide enables efficient removal of H2 antigen from erythrocytes and thereby accomplishes the conversion of regular human type‐O blood into a potential blood substitute for the rare Bombay blood type.

Design of Artificial Glycosidases: Metallopeptides that Remove H Antigen from Human Erythrocytes.

Catalysts that promote carbohydrate degradation have a wide range of potential applications, but the use of either enzyme glycosidases or small-molecule catalysts in biological systems raises significant challenges. Herein, we demonstrate a novel strategy for the design of synthetic agents that mimic natural glycosidases and address current problems for biological use. This strategy is illustrated by application to the development of potential blood substitutes for the rare Bombay blood type that is characterized by a deficiency of H2 antigen. Metallopeptides with 16 to 20 amino acids were constructed as artificial fucosidases that exhibit selective carbohydrate cleavage reactivity toward l-fucose over d-glucose. Selective fucose cleavage from the H2-antigen saccharide enables efficient removal of H2 antigen from erythrocytes and thereby accomplishes the conversion of regular human type-O blood into a potential blood substitute for the rare Bombay blood type.

P142 Hyperacute rejection in a kidney transplant recipient with no HLA antibodies

A 65 year old, blood group O, African-American male with 0% CPRA received a blood group O deceased donor kidney transplant with a negative crossmatch (XM). During surgery, the transplanted kidney became dusky within minutes of restoring blood flow. There was no suspicion of anti-HLA or anti-ABO antibodies which could mediate hyperacute rejection, so a thrombotic event or anatomical defect was suspected. The OPO consented to allocate the second kidney from the same donor; it was transplanted within hours, and the same events transpired. Three days later, the recipient had bleeding and pain at the graft site, and donor vein and artery grafts had to be removed. We sought to identify the factors which caused the allografts loss. Both kidneys were sent for microscopic and C4d evaluation. Recipient HLA antibodies were tested by FlowPRA and Luminex Single Antigen Beads (LSAB). XM were performed by CDC and flow cytometry. Recipient serum was tested for MICA antibodies by LSAB, endothelial cell (EC) antibodies by XM, AT1R antibodies by ELISA, and non-ABO blood group antibodies. Molecular blood typing of the donor DNA was performed. Histopathology identified karyorrhectic nuclear debris in the glomeruli, small fibrin thrombi, and neutrophilic infiltrates, consistent with hyperacute rejection, although IHC failed to show definite C4d deposition. All FlowPRA, XM, LSAB, MICA, and EC XM tests were negative. The AT1R result was 14 U/mL (at risk). Molecular testing confirmed the donor as Group O. Testing ruled out the rare Bombay phenotype, and the recipient was negative for all non-ABO blood group antibodies, except for weak cold agglutinins only seen at 4 °C. The events during the surgery and the pathology findings are consistent with humoral hyperacute rejection. Confoundingly, the recipient has no HLA antibodies and had negative CDC and flow XM with the donor. However, none of the other testing has been able to identify an antibody with a strength that would explain hyperacute rejection. The only identified antibodies thus far are anti-AT1R and cold agglutinins. We are continuing to investigate more non-HLA antibodies that may have a synergistic impact on graft rejection.

History and Development of Genetics Research in India: Three case studies

The paper discusses three major contributions in genetics research from India; Genetic and cytogenetic studies on sugarcane undertaken at the Sugarcane Breeding Institute in Coimbatore during 1912- 1938 by C. A. Barber, T. S. Venkatraman, and E. K. Janaki Ammal, the publication of D. D. Kosambi’s mapping function (1944), and the discovery of the Bombay blood group in KEM Hospital, Mumbai by Y.M. Bhende and co-workers in 1952. Most current research on these topics is now done outside India, possibly because India never developed the critical mass of researchers to sustain the early leads of these pioneers.

Indian Bombay phenotype: it is different!

Indian Bombay phenotype: it is different!

Correlation between 'H' blood group antigen and Plasmodium falciparum invasion.

The ABO blood group system is the most important blood group system in clinical practice. The relationship between Plasmodium falciparum and ABO blood groups has been studied for many years. This study was undertaken to investigate the abilities of different blood group erythrocytes to support in vitro growth of P. falciparum parasites. P. falciparum parasites of four different strains (3D7, 7G8, Dd2 and RKL9) were co-cultured with erythrocytes of blood group 'A', 'B', 'O' (n = 10 for each) and 'O(h)' (Bombay group) (n = 7) for 5days. Statistically significant differences were observed on the fourth day among the mean percent parasitemias of 'O', non-'O' ('A' and 'B') and 'O(h)' group cultures. The parasitemias of four strains ranged from 12.23 to 14.66, 11.68 to 13.24, 16.89 to 22.3, and 7.37 to 11.27% in 'A', 'B', 'O' and Bombay group cultures, respectively. As the expression of H antigen decreased from 'O' blood group to 'A' and 'B' and then to Bombay blood group, parasite invasion (percent parasitemia) also decreased significantly (p < 0.01) and concomitantly, indicating the association of parasite invasion with the amount of H antigen present on the surface of erythrocyte. Thus, the question arises, could H antigen be involved in P. falciparum invasion? To evaluate erythrocyte invasion inhibition, 'O' group erythrocytes were virtually converted to Bombay group-like erythrocytes by the treatment of anti-H lectins extracted from Ulex europaeus seeds. Mean percent parasitemia of lectin-treated cultures on the fourth day was significantly lower (p < 0.05) than that of non-treated cultures and was found to be similar with the mean percent parasitemia demonstrated by the Bombay group erythrocyte cultures, thus further strengthening the hypothesis.

Molecular basis of Bombay phenotype in Mashhad, Iran: identification of a novel FUT1 deletion.

Bombay phenotype is characterized by the lack of H substance both on red blood cell (RBC) surface and in body secretions. Mutations of fucosyltransferase 1 (FUT1) and fucosyltransferase 2 (FUT2) genes are resulted in this rare phenotype. Five unrelated patients were tested by hemagglutination and adsorption/elution techniques for the presence of ABH antigens. The saliva specimens were analysed by hemagglutination inhibition method. The exons 6 and 7 of ABO gene were sequenced to determine ABO genotype. The coding fragments of FUT1 and FUT2 were amplified and sequenced by specific primers. Serologic investigation confirmed Bombay phenotype in all individuals. FUT1 molecular analysis revealed a novel large deletion. Also two novel homozygous mutations were detected; one was a missense mutation (392T>C, L131P) and the other a three nucleotide deletion (668_670delACT, Y224del). FUT2 sequencing showed one reported null allele (428G>A, W143X) and one homozygous deletion of FUT2. Although FUT2 deletion has been reported, this is the first report of FUT1 deletion. Finding two FUT1 novel alleles in Iranian people is indicative of mutation diversity in this gene.

Bombay blood phenotype: Laboratory detection and transfusions recommendations

Four main blood types routinely identified today are A, B, AB, and O. Universal donors have type "O" blood, and have no "A" or "B" antigens. In turn, no blood reactions will occur in recipients. Conversely, universal recipients having type "AB" blood will have no antibodies to the "A" or "B" antigens. Bombay phenotype has no "A" or "B" antigens, classifying it as "O" blood type. Furthermore, Bombay phenotype lacks expression of the H antigen, which is present on every blood cell. When mixed with any type of blood other than Bombay blood, hemolytic reactions occur. A 55-year-old male had his blood typed and screened after trauma activation for an eye injury. On forward grouping, the patient was identified as blood type "O". On reverse grouping, agglutination occurred. Laboratory procedures were evaluated and an expanded antigen panel was performed which confirmed this agglutination, which led to the suspicion of a rare blood type. The patient did not require blood transfusion and was further evaluated by New York Blood Center where the diagnosis of Bombay Phenotype was confirmed. This case emphasizes the importance of proper laboratory investigations for rare blood types, preventative strategies, as well as management of Bombay blood type.

The H blood group system

The H blood group system, ISBT symbol H (018), consists of a single antigen (H) defined by a terminal fucose residue found on red blood cells and in secretions formed by the action of α-1,2-fucosyltransferases 1 (α2FucT1) and 2 (α2FucT2), respectively. Mutant alleles of the corresponding FUT1 and FUT2 genes result in either a H– phenotype (Bombay phenotype, Oh) or a weak H phenotype (para-Bombay, H+w). In addition, the FUT2 gene is the molecular basis of the secretor (Se) status, and homozygosity or compound heterozygosity for null alleles is associated with the nonsecretor (se) status. H– individuals have natural anti-H (mostly IgM), which can cause severe hemolytic transfusion reactions with intravascular hemolysis.

Classical Bombay phenotype in a 26-year-old male donor

Classical Bombay phenotype in a 26-year-old male donor