Comparison of the Detection Rate and Specificity of Irregular Red Blood Cell Antibodies Between First-Time Pregnant Women and Women With a History of Multiple Pregnancies Among 18,010 Chinese Women.

Background: There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant women. Methods: Using the microcolumn gel antiglobulin method, 18,010 Chinese women with a history of pregnancy and pregnant women were screened for irregular RBC antibodies, and for those with positive test results, antibody specificity was determined. The detection rate and specificity of irregular RBC antibodies in women with a history of multiple pregnancies (two or more) and first-time pregnant women were determined. Results: In addition to 25 patients who passively acquired anti-D antibodies via an intravenous anti-D immunoglobulin injection, irregular RBC antibodies were detected in 121 (0.67%) of the 18,010 women. Irregular RBC antibodies were detected in 93 (0.71%) of the 13,027 women with a history of multiple pregnancies, and antibody specificity was distributed mainly in the Rh, MNSs, Lewis, and Kidd blood group systems; irregular RBC antibodies were detected in 28 (0.56%) of the 4983 first-time pregnant women, and the antibody specificity was distributed mainly in the MNSs, Rh, and Lewis blood group systems. The difference in the percentage of patients with irregular RBC antibodies between the two groups was insignificant (χ 2 = 1.248, P > 0.05). Of the 121 women with irregular RBC antibodies, nine had anti-Mur antibodies, and one had anti-Dia antibodies; these antibodies are clinically important but easily missed because the antigenic profile of the reagent RBCs that are commonly used in antibody screens does not include the antigens that are recognized by these antibodies. Conclusion: Irregular RBC antibody detection is clinically important for both pregnant women with a history of multiple pregnancies and first-time pregnant women. Mur and Dia should be included in the antigenic profile of reagent RBCs that are used for performing antibody screens in the Chinese population.

Severe autoimmune hemolytic anemia complicating hereditary spherocytosis treated successfully with glucocorticoids and cyclosporine: a case report.

BACKGROUND: Severe autoimmune hemolytic anemia complicating hereditary spherocytosis is life threatening and has not been described in a case report. Here, we report a case in which this intractable disease was treated successfully with glucocorticoids and cyclosporine. CASE PRESENTATION: A 25-year-old female patient with hereditary spherocytosis developed severe autoimmune hemolytic anemia after respiratory syncytial virus infection. Her hemoglobin level was 26 g/L and various anti-red blood cell antibodies were detected in her serum, making blood matching difficult. Glucocorticoid monotherapy was ineffective. With the addition of cyclosporine (50 mg/12 h), the patient's hemoglobin level increased significantly and the symptoms associated with anemia were greatly relieved. CONCLUSION: In patients with severe autoimmune hemolytic anemia, especially when the presence of multiple anti-red blood cell antibodies and alloantibodies interferes with blood matching, a glucocorticoid-cyclosporine regimen may be tried.

The monocyte monolayer assay, an in vitro method for prediction of in vivo survival of transfused incompatible red blood cells: a review.

It has long been a goal of transfusion medicine scientists to predict which patients will make clinically significant antibodies when transfused with donor red blood cells (RBCs). But this goal has yet to be achieved. Not all patients have an adverse response to an RBC transfusion by making an antibody to an RBC antigen, and for patients who do, in most cases, they form antibodies to common antigens for which provision of antigen-negative RBCs is not difficult. However, for patients who make antibodies to many antigens and for patients who make an antibody requiring rare blood that is negative for a high-prevalence antigen, knowing the clinical significance of that patient's antibody is important for effective and timely transfusion. This review of the literature provides information on the monocyte monolayer assays (MMAs) developed to predict the outcome of incompatible RBC transfusion. One of these assays has been used for almost 40 years in the United States to predict the outcome of RBC transfusion in patients with alloantibodies for whom provision of rare RBCs is very difficult. Because all transfusion medicine facilities and blood centers will not likely implement the MMA, it is important that the selection of the referral laboratory be carefully made. The MMA is a proven test in the prediction of incompatible transfusion outcomes in patients with IgG-only antibodies. It has been helpful in decision-making when rare blood components are not available or not available quickly, although decisions on blood transfusion must be made by the physician attending the patient and blood should not be withheld waiting for the MMA result in an urgent situation.

A comparative study on perinatal outcomes of red blood cell-alloimmunized pregnancies with anti-RhD in combination and anti-RhD alone in China.

BACKGROUND AND OBJECTIVES: The advent of intrauterine transfusion (IUT) has improved the survival of severe foetal anaemia. The aim of this study was to compare the perinatal outcomes of red blood cell (RBC)-alloimmunized pregnancies with anti-RhD in combination and anti-RhD alone in China. MATERIALS AND METHODS: A retrospective study was conducted involving RBC-alloimmunized pregnancies with anti-RhD in combination and anti-RhD alone admitted to The First Affiliated Hospital, Sun Yat-sen University, between January 2007 and December 2019. Obstetric data and neonatal outcomes were compared. RESULTS: A total of 165 alloimmunized pregnancies were identified, with 32 pregnancies in the anti-RhD-in-combination group (25 pregnancies with anti-RhD + anti-RhC and 7 pregnancies with anti-RhD + anti-RhE) and 133 pregnancies in the anti-RhD-alone group. The anti-RhD-in-combination group had significantly higher frequency of IUTs than the anti-RhD-alone group (59.4% [19/32] vs. 30.1% [40/133]; p < 0.01). The postnatal frequency of top-up transfusions was significantly higher in the anti-RhD in combination group than the anti-RhD-alone group (90.6% [29/32] vs. 70.7% [94/133]; p = 0.02). There was no significant difference in the frequency of exchange transfusions (ETs) between the two groups (15.6% [5/32] vs. 17.3% [23/133]; p = 0.82). CONCLUSIONS: Compared to alloimmunized pregnancies with anti-RhD alone, pregnancies with anti-RhD in combination with anti-RhC or anti-RhE have an increased requirement for antenatal IUTs and postnatal top-up transfusions but do not have an increased need for ETs.

A comparison of three column agglutination tests for red blood cell alloantibody identification.

OBJECTIVE: Commercial kits of column tests for pre-transfusion testing have progressively replaced conventional tube tests in most laboratories. Aim of this study was to compare three commercial test cell panels for the identification of irregular red blood cell (RBC) alloantibodies. Overall, 44 samples with a positive indirect antiglobulin test (IAT) by routine testing were used for comparison of following panels: Ortho RESOLVE® panelC (Ortho Clinical Diagnostics (OCD), Milan, Italy), ID-DiaPanel(-P) (Bio-Rad Laboratories, CA, USA) and Identisera Diana(P) (Grifols, Barcelona, Spain). Column agglutination techniques were used, with microtubes containing either microgel (Bio-Rad/Grifols) or glass bead microparticles (Ortho). RESULTS: Alloantibody identification was possible in 38 samples, of which identical identification was shown in 33 samples by all methods. The remaining samples showed differences between certain methods, with the gel card system being superior to the glass card system for analyzing stored samples Considering that not all samples were evaluated in all three methods, the concordance rate reached 100% between Bio-Rad and Grifols, 90.5% between Bio-Rad and OCD, 86.5% between OCD and Grifols and 90.5% between all methods. Although differences in sensitivities were seen for specific antibodies, the three methods showed comparable performance for the identification of RBC alloantibodies.

Predicting anti-Kell-mediated hemolytic disease of the fetus and newborn: diagnostic accuracy of laboratory management.

BACKGROUND: There is controversy on critical cut-off values of laboratory testing to select pregnancies at increased risk for anti-Kell-mediated hemolytic disease of the fetus and newborn. Without early detection and treatment, anti-Kell-mediated hemolytic disease of the fetus and newborn may result in progressive fetal anemia, fetal hydrops, asphyxia, and perinatal death. OBJECTIVE: We aimed to determine the value of repeated anti-Kell titer determination and biological activity measurement using the antibody-dependent cellular cytotoxicity test determination in the management of pregnancies at risk for anti-Kell-mediated hemolytic disease of the fetus and newborn. STUDY DESIGN: This was a retrospective cohort study of pregnancies with anti-Kell and a Kell-positive fetus, identified from January 1999 through April 2015. Laboratory test results and clinical outcome were collected from the Dutch nationwide screening program and the national reference center for fetal therapy in The Netherlands, the Leiden University Medical Center. Diagnostic accuracy was measured (receiver operating characteristic curves, sensitivity, specificity, positive and negative predictive values) for anti-Kell titers and antibody-dependent cellular cytotoxicity test. The relationship between the titer and antibody-dependent cellular cytotoxicity measurements and the 2 foregoing measurements were computed with a Pearson product-moment correlation coefficient. RESULTS: In a 16-year unselected cohort, representing screening results of 3.2 million pregnancies resulting in live births in The Netherlands, we identified 1026 Kell-immunized pregnancies. In all, 93 pregnant women had anti-Kell and a Kell-positive child, without other red cell alloantibodies. In all, 49 children (53%) needed intrauterine or postnatal transfusion therapy. The first anti-Kell titer showed already a high diagnostic accuracy with an area under the curve of 91%. The optimal cut-off point for the titer was 4 (sensitivity 100%; 95% confidence interval, 91-100), specificity 27% (95% confidence interval, 15-43), and positive predictive value 60% (49-71%). The antibody-dependent cellular cytotoxicity test was not informative to select high-risk pregnancies. Linear regression showed no significant change during pregnancy, when antibody titer and antibody-dependent cellular cytotoxicity test results were compared with every 2 foregoing measurements (P < .0001). CONCLUSION: Early determination of the anti-Kell titer is sufficient to select pregnancies at increased risk for hemolytic disease of the fetus and newborn with need for transfusion therapy. If the Kell status of the fetus is known to be positive, a titer of ≥4 can be used to target intensive clinical monitoring.

Clinical and epidemiological profile of alloimmunized and autoimmunized multi-transfused patients against red blood cell antigens in a blood center of Minas Gerais.

BACKGROUND: The large diversity of red blood cell antigens favors, especially in multi-transfused patients, the occurrence of autoimmunization and alloimmunization with the risk of hemolytic transfusion reactions. Thus, this study aimed to determine the rates of alloimmunization and autoimmunization in these individuals, as well as the types of alloantibodies and their systems, clinical and epidemiological aspects and the frequency of autoimmunity in alloimmunized and non-alloimmunized patients. METHODS: In a retrospective study, 153 multi-transfused patients from 2006 to 2014 were evaluated. Sixty-eight had onco-hematological diseases, 64 had hemoglobinopathies and 21 had chronic renal failure. Descriptive analyses were carried out with the proportions being compared using the chi-square test, with the significance level set at 5%. RESULTS: The Rh system was the most frequently involved (53.11%) and anti-E and anti-K (Kell system) were the most prevalent alloantibodies (21.87% each). Autoantibodies were found in ten patients (6.54%) with the percentages of autoimmunization in alloimmunized and non-alloimmunized individuals being 29.16% and 2.32%, respectively (p = 0.0001). There was a significant difference between autoimmunization and the number of transfusions (16.21% in 6-10 vs. 5.26% <6 vs. 2.56% >10; p = 0.0203) and diseases (19.04% in chronic renal failure vs. 6.25% in hemoglobinopathies vs. 2.94% in onco-hematological diseases; p = 0.0329). CONCLUSION: The results show a strong correlation between alloimmunization and autoimmunization. Moreover, they reinforce the need for further studies on the clinical and epidemiological profile of multi-transfused patients in relation to alloimmunity and autoimmunity, especially the latter, for a better understanding of its etiopathogenesis and physiopathogenesis.

Clinical and epidemiological profile of alloimmunized and autoimmunized multi-transfused patients against red blood cell antigens in a blood center of Minas Gerais

ABSTRACT Background: The large diversity of red blood cell antigens favors, especially in multi-transfused patients, the occurrence of autoimmunization and alloimmunization with the risk of hemolytic transfusion reactions. Thus, this study aimed to determine the rates of alloimmunization and autoimmunization in these individuals, as well as the types of alloantibodies and their systems, clinical and epidemiological aspects and the frequency of autoimmunity in alloimmunized and non-alloimmunized patients. Methods: In a retrospective study, 153 multi-transfused patients from 2006 to 2014 were evaluated. Sixty-eight had onco-hematological diseases, 64 had hemoglobinopathies and 21 had chronic renal failure. Descriptive analyses were carried out with the proportions being compared using the chi-square test, with the significance level set at 5%. Results: The Rh system was the most frequently involved (53.11%) and anti-E and anti-K (Kell system) were the most prevalent alloantibodies (21.87% each). Autoantibodies were found in ten patients (6.54%) with the percentages of autoimmunization in alloimmunized and non-alloimmunized individuals being 29.16% and 2.32%, respectively (p = 0.0001). There was a significant difference between autoimmunization and the number of transfusions (16.21% in 6-10 vs. 5.26% <6 vs. 2.56% >10; p = 0.0203) and diseases (19.04% in chronic renal failure vs. 6.25% in hemoglobinopathies vs. 2.94% in onco-hematological diseases; p = 0.0329). Conclusion: The results show a strong correlation between alloimmunization and autoimmunization. Moreover, they reinforce the need for further studies on the clinical and epidemiological profile of multi-transfused patients in relation to alloimmunity and autoimmunity, especially the latter, for a better understanding of its etiopathogenesis and physiopathogenesis.

Caracterización de los antígenos y anticuerpos eritrocitarios en pacientes en espera de trasplante renal / Red blood cell antigens and antibodies in patients awaiting renal transplantation

Introducción: la importancia de los grupos sanguíneos para la terapia transfusional y el trasplante es bien conocida. La presencia de anticuerpos eritrocitarios puede mediar reacciones transfusionales hemolíticas severas y rechazo de trasplante. Objetivo: caracterizar los antígenos y anticuerpos eritrocitarios en pacientes en espera de trasplante renal.Métodos: se realizó un estudio prospectivo en 980 pacientes en espera de trasplante renal considerados aptos para trasplante, en el periodo comprendido entre julio de 2013 y julio de 2014. Se investigó la frecuencia de los grupos sanguíneos ABO, Rh (DCcEe), Kell (K), Duffy, Kidd y Lewis y se realizó la pesquisa de auto y de aloanticuerpos eritrocitarios a través de las prueba de antiglobulina directa e indirecta (Coombs) y la técnica de polietilenglicol. Resultados : el grupo sanguineo 0 fue el más frecuente, seguido del A, el B y el AB. Dentro de los fenotipos RhD positivos, el DCCee predominó en los individuos blancos y el Dccee en los no blancos. El RhD negativo (ccee) fue más frecuente en blancos que en no blancos. La distribucion del antigeno Kell fue similar en ambos grupos. Se identificaron 14 pacientes (1,4 por ciento) con prueba de Coombs directa positiva, y aloanticuerpos eritrocitarios en 35 pacientes, para una frecuencia de aloinmunización eritrocitaria del 3,6 por ciento. Predominaron los anticuerpos anti - Rh y contra el antigeno Kell. La técnica de polietilenglicol detectó un mayor número de anticuerpos que la PAI, especialmente contra el antigeno RhD, aunque la comparación no fue estadisticamente significatica. Conclusiones: la frecuencia de aloinmunización eritrocitaria es menor que las comunicadas en otros estudios y se relacionó con los antecedentes transfusionales. Se recomienda realizar la pesquisa de auto y aloanticuerpos eritrocitarios a todos los pacientes con enfermedad renal crónica en lista de espera de trasplante(AU)

Introduction: The importance of blood groups in transfusion therapy and transplant is very well known. The presence of red blood cell antibodies can mediate severe hemolytic transfusion reactions and transplant rejection. Objective: To characterize red blood cell antigens and antibodies in patients awaiting renal transplantation. Methods: A prospective study in 980 patients in waiting list for renal transplantation in the period from July, 2013 to July, 2014 was carried out. The frequency of ABO, Rh (DCcEe), Kell (K), Duffy, Kidd and Lewis blood groups, and the screening of red blood cells auto and alloantibodies by the direct and indirect antiglobulin test (Coombs) and the polietilenglicol technique were investigated. Results: Blood group O was the most frequent followed by A, B and AB. DCCee phenotype was frequent in white individuals and Dccee in non-white. RhD negative (ccee) was more frequent in whites than in non-whites. Distribution of Kell antigen was similar in both groups. Direct antiglobulin test was positive In 14 patients (1,4 percent) and red blood cell alloantibodies were identified in 35 patients for a frequency of alloimmunization of 3,6 percent. Anti-Rh anti-K antibodies were the alloantibodies most frequently identified. The polietilenglicol technique detected a higher number of antibodies than the indirect antiglobulin test, specially against RhD antigen, although the comparison was not statistically significant. Conclusions: The frequency of alloimmunization is smaller than those communicated in other studies which was related to transfusion records. A periodic red blood cell auto and alloantibodies screening is recommended in all patients awaiting renal transplantation(AU)

Caracterización de los antígenos y anticuerpos eritrocitarios en pacientes en espera de trasplante renal / Red blood cell antigens and antibodies in patients awaiting renal transplantation

Introducción : la importancia de los grupos sanguíneos para la terapia transfusional y el trasplante es bien conocida. La presencia de anticuerpos eritrocitarios puede mediar reacciones transfusionales hemolíticas severas y rechazo de trasplante.Objetivo : caracterizar los antígenos y anticuerpos eritrocitarios en pacientes en espera de trasplante renal.Métodos: se realizó un estudio prospectivo en 980 pacientes en espera de trasplante renal considerados aptos para trasplante, en el periodo comprendido entre julio de 2013 y julio de 2014. Se investigó la frecuencia de los grupos sanguíneos ABO, Rh (DCcEe), Kell (K), Duffy, Kidd y Lewis y se realizó la pesquisa de auto y de aloanticuerpos eritrocitarios a través de las prueba de antiglobulina directa e indirecta (Coombs) y la técnica de polietilenglicol.Resultados : el grupo sanguineo "0" fue el más frecuente, seguido del A, el B y el AB. Dentro de los fenotipos RhD positivos, el DCCee predominó en los individuos blancos y el Dccee en los no blancos. El RhD negativo (ccee) fue más frecuente en blancos que en no blancos. La distribucion del antigeno Kell fue similar en ambos grupos. Se identificaron 14 pacientes (1,4 por ciento) con prueba de Coombs directa positiva, y aloanticuerpos eritrocitarios en 35 pacientes, para una frecuencia de aloinmunización eritrocitaria del 3,6 por ciento. Predominaron los anticuerpos anti - Rh y contra el antigeno Kell. La técnica de polietilenglicol detectó un mayor número de anticuerpos que la PAI, especialmente contra el antigeno RhD, aunque la comparación no fue estadisticamente significatica.Conclusiones: la frecuencia de aloinmunización eritrocitaria es menor que las comunicadas en otros estudios y se relacionó con los antecedentes transfusionales. Se recomienda realizar la pesquisa de auto y aloanticuerpos eritrocitarios a todos los pacientes con enfermedad renal crónica en lista de espera de trasplante(AU)

Hemolytic disease of the fetus and newborn due to multiple maternal antibodies.

OBJECTIVE: The objective of the study was to determine whether women with combinations of red blood cell antibodies are more likely to develop significant hemolytic disease of the fetus and newborn than those with single antibodies. STUDY DESIGN: A retrospective exposure cohort study was conducted of pregnant women with red blood cell antibodies. The development of significant hemolytic disease of the fetus and newborn was then compared between patients with single antibodies and those with multiple antibodies. Data analysis was limited to pregnancies delivering since the year 2000. RESULTS: Thirteen percent of the patients referred to our program had multiple red blood cell antibodies. Odds of developing significant hemolytic disease of the fetus and newborn for patients with anti-Rh(D) combined with at least 1 additional red blood cell antibody were 3.65 times the odds for women with anti-Rh(D) antibodies in isolation (95% confidence interval, 1.84-7.33). In the setting of multiple antibodies including anti-Rh(D), Rh-positive fetuses/neonates have an increased odds of developing significant hemolytic disease even if the fetus is negative for the other corresponding red blood cell antigen. CONCLUSION: Women with multiple red blood cell antibodies are more likely to develop significant hemolytic disease of the fetus and newborn than those with a single antibody especially in the presence of anti-(Rh)D. This pathophysiology may suggest a more aggressive immune response in women who develop more than 1 red blood cell antibody.

REGGI and the American Rare Donor Program.

The American Rare Donor Program (ARDP) was formed in 1998 to provide rare blood units for patients in need. Members of the program identify rare donors and submit donor information for entrance into a database, REGGI. Information on patients in need of rare blood is also submitted and entered into REGGI. REGGI serves to match phenotypes of registered donors with patients having the respective antibodies. A search process for available units ensues, and blood is provided to the patient. This report provides information on REGGI and its use in the ARDP.

Responder individuality in red blood cell alloimmunization.

Many different factors influence the propensity of transfusion recipients and pregnant women to form red blood cell alloantibodies (RBCA). RBCA may cause hemolytic transfusion reactions, hemolytic disease of the fetus and newborn and may be a complication in transplantation medicine. Antigenic differences between responder and foreign erythrocytes may lead to such an immune answer, in part with suspected specific HLA class II associations. Biochemical and conformational characteristics of red blood cell (RBC) antigens, their dose (number of transfusions and pregnancies, absolute number of antigens per RBC) and the mode of exposure impact on RBCA rates. In addition, individual circumstances determine the risk to form RBCA. Responder individuality in terms of age, sex, severity of underlying disease, disease- or therapy-induced immunosuppression and inflammation are discussed with respect to influencing RBC alloimmunization. For particular high-risk patients, extended phenotype matching of transfusion and recipient efficiently decreases RBCA induction and associated clinical risks.

A comparison of two automated methods for the detection and identification of red blood cell alloantibodies.

BACKGROUND: The aim of this study was to compare the routine use of two automated systems (OrthoAutoVue Innova, microcolumn, and Immucor Galileo, solid phase) for the screening and identification of irregular red blood cell alloantibodies in samples, analysed in our Transfusion Service during 6 months of normal activity. The study focused particularly on an evaluation of the repeatability of the screening tests, the identification of antibody specificities and the identification of antibodies in samples showing discordant results. MATERIALS AND METHODS: Overall 2,229 samples from potential blood donors (A), multiply transfused patients with blood disorders (DH), potential transfusion recipients (TS), and external cases (E) were studied. The protocols were carried out according to the manufacturers recommendations. RESULTS: The screening tests detected 78 samples that were positive with both systems, while 18 were positive only with Immucor and 11 only with Ortho (thus, overall, Immucor detected 96 positive samples and Ortho 89 positive samples). The use of the respective identification panels enabled us to identify the antibodies in 65 samples with Immucor and in 61 samples with the Ortho system; 74 antibodies were identified with Immucor (55 with a single specificity and 19 with mixed specificities) and 68 antibodies with Ortho (51 and 17, respectively). In the remaining cases (31 samples for Immucor and 28 for Ortho), the antibody specificity was not identified. The two systems were found to be essentially similar. The Immucor system revealed a greater number of antibodies, mainly because of its greater sensitivity at detecting anti-D antibodies. CONCLUSIONS: Both systems showed a repeatability of over 85%, demonstrating that automation of immunohaematological tests is advantageous. The specificity of the antibody was identified in 68% of the samples. Furthermore, using the two systems led to the identification of ten new antibodies (6 anti-D, 2 anti-E, 1 anti Le(a), and 1 anti-Vel), which would not have been detected had only one of the two methods been used.