Prevention of hemolytic transfusion reactions with intravenous immunoglobulin prophylaxis in U- patients with anti-U.

BACKGROUND: The U- phenotype is extremely rare and is found predominantly in black African populations at a frequency of between 0.2 and 1.7%. In European populations, U- units are therefore rare, with limited availability in the United Kingdom. Anti-U is clinically significant and is known to cause hemolytic transfusion reactions (HTRs) and hemolytic disease of the fetus and newborn. It has been suggested that intravenous immunoglobulin (IVIG) may be considered as an option among supportive therapy for urgent transfusion when clinically significant antigen-matched units are not available. We report three cases with anti-U transfused with least-incompatible RBC units, their outcomes, and their clinical management. STUDY DESIGN AND METHODS: Intravenous immunoglobulin was prescribed when least-incompatible units must be issued in patients with anti-U to ameliorate acute HTR and prevent the development of delayed HTR. We report the outcome of these cases. RESULTS: Of the case reports described, one patient with weak anti-U developed a delayed HTR after transfusion with incompatible units due to an anamnestic response. Two additional patients are described, with the use of IVIG as a precautionary measure to prevent the development of HTRs when transfused with antigen-positive incompatible units. No acute HTRs or delayed HTRs were noted upon follow-up. CONCLUSION: U- units are not always readily available and transfusion support requires close collaborative working among a multidisciplinary team. Transfusion with antigen-positive incompatible units with IVIG cover both ameliorates acute HTRs and prevents the development of delayed HTRs.

Race/ethnicity is associated with ABO-nonidentical liver transplantation in the United States.

United Network for Organ Sharing (UNOS) policies allow for ABO-nonidentical liver transplantation (LT) in candidates with Model for End-Stage Liver Disease (MELD) scores greater than 30. Previous studies showed ABO-nonidentical LT resulted in an 18% and 55% net gain in livers for B and AB candidates. These results suggested that the current liver ABO allocation policies may need refinement. There are, however, strong associations between ABO blood groups and race/ethnicity. We hypothesized that race/ethnicity is associated with ABO-nonidentical LT and that this is primarily influenced by recipient ABO status. We examined non-status 1 adult candidates registered between July 1, 2013, and December 31, 2015. There were 27 835 candidates (70% non-Hispanic White, 15% Hispanic, 9% Black, 4% Asian, 1% Other/Multiracial). A total of 11 369 underwent deceased donor LT: 93% ABO identical, 6% ABO compatible, and 1% ABO incompatible. Black and Asian race/ethnicity were associated with increased likelihoods of ABO-nonidentical LT. Adjustment for disease etiology, listing MELD, transplant center volume, and UNOS region did not alter this association. Stepwise inclusion of recipient ABO status did eliminate this significant association of race/ethnicity with ABO-nonidentical LT. Blacks and Asians may be advantaged by ABO-nonidentical LT, and we suspect that changes to the existing policies may disproportionately impact these groups.

Neonatal BO Incompatibility Is Associated With a Positive Cord Blood Direct Antiglobulin Test in Infants of Black Ethnicity.

ABO hemolytic disease of the newborn occurs almost exclusively in infants of blood group A and B who are born to group O mothers. Positive Direct Antiglobulin Test (DAT) can identify those infants who are at risk of developing the ABO hemolytic disease. Earlier studies have suggested that BO incompatibility is associated with a positive DAT in black infants. In this study we sought to determine whether ABO incompatibility type could be associated with a higher rate of DAT positivity or clinical hemolytic disease. We reviewed the electronic medical records of all ABO-incompatible births over a 2-year period. There were 1537 ABO-incompatible births during the study period. DAT was more commonly positive among BO incompatible (21.5% in BO vs. 14.8% in AO, P=0.001) and black (18.8% in blacks vs. 10.8% in nonblacks, P=0.003) infants. DAT positivity was significantly associated with both severe hyperbilirubinemia (P=0.028) and hemolytic anemia (P<0.001). BO incompatibility was significantly associated with hemolytic anemia, but not severe hyperbilirubinemia, in the infants tested.

Risk estimation of HNA-3 incompatibility and alloimmunization in Thai populations.

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.

[From donor to recipient: transfusion chain specificities in the French ultra-marine areas]. / Du donneur au receveur: particularités de la chaîne transfusionnelle dans les DOM.

Besides specific organisational requirements, the transfusional chain in French ultra-marine areas has specificities related to the epidemiology of infectious diseases and to population characteristics. We focus on some of these sociodemographic and medical peculiarities: the challenge of autosufficiency in relation to demographic trends; epidemiologic risks associated to emergent viruses such as dengue and Chikungunya, and the strategies that had been implemented to face last outbreaks; inappropriate selection criteria for eligibility to blood donation (biologic characteristics of Afro-Caribbeans not taken into account for the low hemoglobin deferral threshold; absence of guidelines for the screening of hemoglobinopathies AS/AC, present in 8% of the target population); specific indications for transfusion, such as platelet use in dengue fever or RBC transfusion in sickle cell disease. Due to the high polymorphism of erythrocyte antigens in Afro-Caribbeans, intra-ethnic transfusion facilitates compatibility for common antigens, but is responsible for the emergence of allo-antibodies difficult to identify in the absence of specific antisera or panels; molecular typing of erythrocyte antigens would allow detection of those patients at risk for immunization, expressing variant antigens or lacking high frequency antigens, as well as the characterization of RBC expressing immunogenic so called low frequency antigens. In an era of periodic emergence of new viruses in Europe (dengue, Chikungunya, West Nile virus...) and with the spreading of diseases with high transfusional requirements, such as sickle cell disease, ultra-marine services represent laboratories for the study of future trends and problems in transfusion medicine.

Determination of neutrophil antigen HNA-3a and HNA-3b genotype frequencies in six racial groups by high-throughput 5' exonuclease assay.

BACKGROUND: People with the human neutrophil antigen (HNA)-3b/3b type can make HNA-3a antibodies, which have been reported to cause immune neutropenia disorders and are especially prone to cause severe cases of transfusion-related acute lung injury. However, knowledge of HNA-3 allele frequencies outside Caucasian populations is limited. We developed a high-throughput genotyping assay and determined the HNA-3a/3b genotype frequencies in six different racial and ethnic groups. STUDY DESIGN AND METHODS: Genotyping utilized TaqMan 5' exonuclease chemistry and real-time polymerase chain reaction. A total of 742 DNA samples from six different racial and ethnic groups were genotyped for HNA-3a and HNA-3b. RESULTS: The genotyping assay showed 100% sensitivity and specificity compared to sequencing and phenotyping and had high throughput. A significant percentage of Caucasians (6.5%), Han Chinese (16%), and Asian Indians (6%) typed HNA-3b/3b, but only a small percentage of Hispanics (1%) and no African or Native Americans. CONCLUSIONS: The HNA-3 genotyping assay had high sensitivity, specificity, and sample throughput. HNA-3b/b genotype results determined for 742 individuals representing six different racial and ethnic groups showed that there could be a significant risk of producing anti-HNA-3a in Chinese, as well as in Caucasian and Asian Indian blood donor populations, but a very low risk in Hispanic, African, or Native American populations.

Red blood cell phenotype matching for various ethnic groups.

Patients requiring chronic transfusion support are at risk of alloimmunization after red blood cell (RBC) transfusion because of a disparity between donor and recipient antigen profiles. This research explored the probability of obtaining an exact extended phenotype match between blood donors randomly selected from our institution and patients randomly selected from particular ethnic groups. Blood samples from 1,000 blood donors tested by molecular method were evaluated for the predicted phenotype distribution of Rh, Kell, Kidd, Duffy, and MNS. A random subsample of 800 donor phenotypes was then evaluated for the probability of obtaining an exact match with respect to phenotype with a randomly selected patient from a particular ethnic group. Overall, there was a greater than 80 percent probability of finding an exact donor-recipient match for the K/k alleles in the Kell system. The probability ranged from 3 percent to 38 percent, depending on the ethnicity and disparities in phenotypic profiles, for the Rh, Kidd, Duffy, and MNS systems. A significant donor-recipient phenotype mismatch ratio exists with certain blood group antigens such that, with current routine ABO and D matching practices, recipients of certain ethnic groups are predisposed to alloimmunization.

Hydrops fetalis due to ABO incompatibility.

Antenatal haemolysis in association with ABO incompatibility occurs very rarely. Two cases of hydrops fetalis in black infants caused by anti-B haemolysins are reported. The greater severity of ABO incompatibility in black African peoples may have important implications for antibody screening in this ethnic group.

Incidence of the Nak(a)-negative platelet phenotype in African Americans is similar to that of Asians.

BACKGROUND: About 5 to 10 percent of Asians have platelets that lack the major membrane glycoprotein (GP) IV (CD36, GPIIIb) that carries the isoantigen Naka. The GPIV-negative platelet phenotype is extremely rare among whites, but its frequency in persons of African ancestry has not yet been determined. Isoimmunization against GPIV can occur in GPIV-negative persons and can lead to platelet transfusion refractoriness. Therefore, the expression of GPIV on platelets from unrelated African Americans was studied. STUDY DESIGN AND METHODS: Platelets were obtained from 250 African American and 280 white blood donors. Flow cytometry was used to determine the ability of these platelets to bind a monoclonal antibody that reacted with GPIV. Platelets that failed to react with this probe were tested with other GPIV-specific monoclonal antibodies and with anti-Naka, an isoantibody that recognizes an epitope on GPIV. RESULTS: Platelets from 6 of the 250 African American donors (2.4%) lacked GPIV and failed to bind anti-Naka, whereas platelets from all of the white donors were GPIV positive (p>0.05). No platelet-reactive antibodies were identified in the serum of the GPIV-negative donors. CONCLUSION: The frequency of the GPIV-negative platelet phenotype in African Americans is comparable to that in Asians and much greater than that in whites. Studies are needed to determine the frequency with which African Americans become isoimmunized to GPIV by transfusions and the possible contribution of this isoimmunization to platelet transfusion refractoriness in this population.

Risk estimation of ABO and Rho(D) incompatibility in persons with mono- and polyphyletic surnames in Monterrey, Mexico: comparison with other Mexican population

ABO and Rho(D) blood groups were determined in 3813 males and females affiliated with the Instituto Mexicano del Seguro Social (IMSS) who are residents of the Monterrey Metropolitan Area (MMA) in northeastern Mexico. They were selected by their monophyletic or polyphyletic surnames. The ABO and Rho(D) blood group phenotypes and gene frequencies were determined and based upon these, the risk of incompatibilities was estimated for both marriages (MI) and maternal-fetal incompatibility (MFI). These were compared with those estimated for other populations of residents in the MMA, and in other locations in Mexico, as well as with the two most important ancestral populations, Spanish and Tlaxcaltecan Mexican Indians, with the hypothesis that the percent of risk ABO and Rho(D) MI and MFI are greater in the population with monophyletic surnames than those with polyphyletic surnames. It was found that for persons with nomophyletic and polyphyletic surnames, as well as for the other populations in the MMA and other places in Mexico, their ABO and Rho(D) MI and MFI percent of risk are intermediate to the ones estimated for their ancestry. The percentages of MI and MFI are higher for the persons with monophyletic than for the ones with polyphyletic surnames, other populations from the MMA and those from other locations in Mexico. The risks are higher when the similarity with Spanish increases and are lower when their similarities with the mexican Indians increase

Blood transfusion in the para-Bombay phenotype.

The H-deficient phenotypes found in Chinese so far, have all been secretors of soluble blood group substances in saliva. The corresponding isoagglutinin activity (e.g. anti-B in OB(Hm) persons) has been found to be weak in all cases. To determine the clinical significance of these weak isoagglutinins 51Cr red cell survival tests were performed on three OB(Hm) individuals transfused with small volumes (4 ml) of groups B and O RBC. Rapid destruction of most of the RBC occurred whether or not the isoagglutinins of the OB(Hm) individuals were indirect antiglobulin test (IAGT) reactive. When a larger volume (54 ml packed RBC) of group B cells (weakly incompatible by IAGT) was transfused to another OB(Hm) individual with IAGT active anti-HI, the survival of the transfused RBC was 93% at 24 h, with 30% of the RBC remaining in the circulation at 28 d in contrast to 76% as would be expected if the survival was normal. Therefore when whole units of blood of normal ABO blood groups, compatible by IAGT, are transfused, the survival is expected to be almost normal. These weak isoagglutinins may not be very clinically significant and we suggest that when para-Bombay blood is not available, the compatibility testing for OA(Hm) persons should be performed with group A and group O packed RBC; OB(Hm) with group B and group O packed RBC: OAB(Hm) with groups A, B, AB and O packed RBC. For cross matching, the indirect antiglobulin test by a prewarmed technique should be used.

Incidence of Rh anti-E and anti-c production among Japanese after blood transfusion.

The incidence of Rh anti-E antibody production due to blood transfusion in the patients who were Rh E negative and were transfused with more than one unit (200 ml) of E positive red blood cells was examined. The anti-E was detected in 17 (4.7%) out of 360 patients. The incidence of anti-E was significantly higher in the patients who had previously received transfusion than in those who had not. By a similar method, the anti-c was detected in 4 (1.4%) out of 284 patients. The incidence of anti-E and anti-c production among the Japanese receiving blood transfusion at random is estimated to be 1.17% and 0.35%, respectively.

Haematolytic disease due to ABO incompatibility: incidence and value of screening in an Asian population.

The population in Singapore is predominantly Asian, with Chinese forming the major ethnic group. The incidence of haemolytic disease of the newborn (HDN) due to Rh incompatibility is very low. The true incidence of HDN due to ABO incompatibility is unknown. Early discharge is practised in Singapore making it important to predict severe HDN due to ABO incompatibility as this would constitute the main cause of haemolysis next to G6PD deficiency. One thousand, six hundred and eight baby-maternal pairs were typed for ABO, Rh, and tested for direct Coombs' test, maternal titre, cord bilirubin and haptoglobin levels. Two hundred and fifty-one were found to be ABO incompatible, with 141 group A and 110 group B babies. The incidence of HDN due to ABO incompatibility was 3.7% of all group O mothers. Coombs' test, maternal antibody titre, cord bilirubin and haptoglobin levels were of low predictive value for severe HDN due to ABO incompatibility. The data further support the notion that it is not cost effective to screen for ABO incompatibility.