Unexpected Red Cell Antibodies Research Articles

A voluntary transfusion recipient registry in Korea as a database for blood group antibodies.

Several types of transfusion-related registries have been developed to improve patient outcomes and blood banks. In Korea, a transfusion program functioning as a blood group antibody database and a reference laboratory has been in operation since July 2013. This study was conducted to determine the current status of blood group antigens and antibodies in Korea and propose a model for registries in the field of transfusion medicine. Cases with unexpected red cell antibodies were registered online in the voluntary transfusion registry. Specific antigen-negative frequencies were calculated based on the recorded data. To determine the frequencies of RhCE antigens, data added via the Blood Information Sharing System were also analyzed. Data added to the registries between July 2013 and June 2022 were included in the analysis. Among 9,048 antibody cases registered from 29 hospitals, anti-E alone was identified most commonly, followed by anti-E and c, anti-C and e, anti-Lea, and anti-M (2,202, 1,792, 757, 618, and 383 cases, respectively). The frequencies of E-, E-c-, C-e-, Le(a-), and M- were 49.1%, 41.6%, 9.1%, 69.4%, and 21.8%, respectively. The distributions of antibodies and antigen frequencies were estimated through the transfusion registry. Antigen frequencies were calculated based on the results of antigen typing of red blood cell components performed at the time of issuing. The online transfusion registry serving as a blood group antibody database is useful for determining the frequencies of blood group antigens and antibodies.

Prevalence of unexpected red blood cell antibodies in pregnant women and follow-up of pregnancy outcome in pregnant women treated with intra-uterine transfusion.

For the management of hemolytic disease of the fetus and newborn (HDFN), it is important to detect unexpected red cell antibody in pregnant women. We assessed the prevalence of unexpected red cell antibodies in consecutive pregnant women attending antenatal clinic (ANC). More importantly, cases with unexpected antibody causing severe anemia were followed-up for intervention (Intra-uterine transfusion {IUT}) and outcome of pregnancy (still-birth/live-healthy). The study was conducted with an objective to find the prevalence of unexpected RBC antibodies in pregnant women, their specificity and to do the follow-up for IUT and outcome of pregnancy (still-birth, live-birth) in antibody positive women. This was a prospective study from January 2021 to May 2022 at two tertiary care centres. All antenatal samples received by the laboratory were screened for unexpected red cell antibody. Whenever antibody screen was positive, antibody identification was performed. Patients, positive for unexpected antibody and anemia were followed up for any transfusion-based intervention and outcome of pregnancy. A total of 539 consecutive samples were worked up and among these, 10 samples (1.85%) were found to be antibody positive. The antibodies identified were Anti-D (n=6), anti-Leb (n=1), anti-M (n=1), anti-C (n=1) and anti-E (n=1).The prevalence of unexpected antibodies in Rh positive and Rh negative pregnant women was 0.83% and 10.9% respectively. Follow-up was done for all 10 cases with unexpected antibody and anemia was monitored by MCA PSV (middle cerebral artery peak systolic velocity).Two women developed severe anemia thus requiring single intrauterine transfusion (at 26 weeks and 28 weeks respectively) each, for correction of anemia. In both these cases, healthy male child was delivered. At 3-month follow-up both children were alive and healthy. The study found prevalence of unexpected RBC antibodies in pregnant women as 1.85%. The study also underlined importance of transfusion-based interventions contributing to successful outcome in couple of cases with severe anemia.

A rare case of clinically significant naturally occurring anti-Cw reported in a healthy male donor.

Anti-Cw antibody is an immunoglobulin against the red cell antigen Cw which is a low frequency red cell antigen that belongs to the Rh antigen system. It is a clinically significant antibody and may cause haemolysis on exposure to antigen positive red cells. Due to its low frequency, it is not included in routine antibody screening panels. A 32years healthy male donor with no history of transfusion donated whole blood at the department of Transfusion Medicine & Blood Centre of our institute. As a part of routine pre-transfusion testing, the donor's samples were subjected to automated blood grouping and screening for unexpected red cell antibodies using 3 cells panel on solid-phase red-cell adherence (SPRCA) (Galileo Neo, Immucor, Norcross, USA). The antibody screening came out to be positive with a reaction in cell I of the antibody screening panel. Further the antibody was identified as anti Cw in using 16 cells panel, select cells and phenotyping. In the present case, the anti-Cw antibody was found to be reactive at 37°C and AHG phase which could lead to haemolytic transfusion reaction. The fact that the male donor had no history of transfusion or transplant led us to the conclusion that it was a naturally occurring, but a clinically significant antibody. This case highlights the importance of performing an antibody screening for healthy donors as well and urges transfusion services to procure screening cells which incorporate Cw positive cells.

Estimation of prevalence of red cell alloantibodies in patients with Beta Thalassaemia Major in Sri Lanka.

Major beta thalassaemia is an inherited haemolytic disease that needs regular blood transfusion as a standard treatment. Blood transfusion is generally safe; however, adverse effects can occur and one of which is red cell alloimmunization that can lead to acute or delayed haemolytic transfusion reactions. This study was designed to estimate the prevalence of red cell alloantibodies in patients with thalassaemia in Sri Lanka. The study was carried out at three tertiary care hospitals of Sri Lanka. Every beta thalassaemia patients transfused with packed red cells were included. Data collected to a form by analysing the cross match request form sent to the blood bank prior to the transfusion. There were 398 patients in all hospitals. 188 (47.24%) of them were males and 210 (52.76%) were females. Mean age was 18.41 (SD=11.67) years. Out of 398 patients, unexpected red cell antibodies are present only in 6 (1.51%) patients. Identified antibodies were Anti E, Anti K, Anti D, Anti C, Anti S, Anti Jkb and autoantibodies. There was one patient who had developed multiple antibodies. Prevalence of red cell antibodies is lower, even though the patients were been transfused without phenotypically matched red cells. Further studies are suggested to decide the practice of Rh and Kell matching for transfusion in patients with beta thalassaemia.

Prevalence of Unexpected Red Cell Antibodies in Healthy Donor Population in a Tertiary Care Center in South Kerala

Background and Objectives: Apart from naturally occurring red cell antibodies Anti-A and Anti-B in human plasma, there are two types of unexpected red cell antibodies: Alloantibodies and auto-antibodies. The presence of these antibodies, alone or in combination, makes difficulties with compatibility testing, thereby delaying in the issue of a compatible blood unit or may reduce posttransfusion red blood cells life span. Antibody screening is mandatory as laid down by the Drug and Cosmetic Act 1940 and Directorate General of Health Services guidelines. This goal of this paper was to study the prevalence of Unexpected Red Cell Antibodies in Healthy Donor Population in a Tertiary Care Centre in South Kerala. Methods: The sample size chosen for this study was 7000 randomly chosen healthy nonremunerated voluntary donors who attended in house and blood donation camps over a period between November 26, 2017, and February 15, 2019. Results: The prevalence of unexpected red cell antibodies was found to be 1 in 1000. Male blood donations were more than female and blood donors among 18–30 years of age were greater in number. There were no cases of direct antiglobulin test positivity encountered. Male: Female ratio is 2.5:1 and males had naturally occurring alloantibodies, whereas females had a previous history of pregnancy. Anti-M and Anti-Lewis antibodies were the most common alloantibodies followed by Anti-Rh (D and C) antibodies and Anti-IH in the current study. Benign cold agglutinins (BCA) were found predominately in the younger male population with a significant seasonal variation noted in the prevalence of these antibodies. Conclusion: All antibodies identified had the ability to cause immune hemolytic transfusion reactions in the recipients. BCA-positive cases were seen more during the winter season and rainy seasons when compared to hot climatic conditions.

Analysis of red cell alloimmunization in multi transfused patients at a Tertiary care teaching hospital.

Background:Red blood cell (RBC) alloimmunization is an immune response against foreign RBC antigens; this generally occurs after sensitization due to multiple blood transfusions and pregnancies. Antibody detection plays a critical role in transfusion medicine as it can detect irregular or unexpected antibodies. This study was done to know the frequency and specificity of unexpected red cell antibodies in the multitransfused patients.Materials and Methods:This prospective study was done in the Department of Immuno-Haematology and Blood Transfusion. Antibody screening of 100 multitransfused patients with initial negative antibody screen was carried out prior to compatibility testing and followed for a period of 12 months for each transfusion. Depending on the results, patients were given corresponding antigen-negative blood units.Results:In this study, the rate of alloimmunization was 7%. Total number of samples that were positive for irregular alloantibodies were 4 of 54 cases of thalassemia, that is, 7.4%, whereas 3 of 40, that is, 7.5%, cases of solid malignancies developed alloantibodies. None of the patients of chronic kidney disease formed any alloantibody. Anti-K antibody was the most frequent antibody detected in 3 of 7, that is, 42.8% patients. Anti-E was the second most frequent antibody observed in 2 of 7, that is, 28.57%. However, anti-c and anti-M were detected in one each of 7, that is, in 14.28% each.Conclusion:It is concluded here that red cell alloimmunization should not be overlooked in multitransfused patients. To avoid the effects of alloimmunization, routine RBC antibody screening at set time intervals after transfusion should be performed.

Prevalence of red blood cell antibodies in whole blood donors: A single-centre experience in north India.

Background & objectives:Blood transfusion therapy involves multiple steps to ensure selection of safe blood component for transfusion. This includes testing for infectious markers, full ABO compatibility, free from any clinically significant red cell antibodies and acceptable donor's red cell survival rates without destruction of recipient's red cells. The red cell antibodies present in healthy blood donors can cause severe haemolytic transfusion reaction, especially in massive blood transfusion recipients and paediatric patients. Hence, screening of red cell antibodies in donor blood is important to provide compatible blood products and to avoid haemolytic transfusion reactions in susceptible patient population. This study was planned to assess prevalence, aetiology and type of unexpected red cell antibodies in a large number of whole blood donor population in north India.Methods:This three-year prospective observational study included blood donor samples for antibody screening from January 2015 to December 2017. A total of 166,803 healthy blood donors including 156,128 (93.6%) males and 10,675 (6.4%) females were screened.Results:The prevalence of red cell antibodies was 0.17 per cent in our donor population. Of the total 286 donors with red cell antibodies, 248 (86.7%) had alloantibodies, 30 (10.5%) had autoantibodies and eight donors (2.8%) showed positive antibody screening with inconclusive results.Interpretation & conclusions:Alloimmunization to red cell antigens is a challenging task for current transfusion practices. The antibody screening in blood donors may improve the quality and safety of blood transfusion in the recipients. It also reduces the risk of complications from incompatible blood transfusions.

Red Cell Antibody Screening: A Single Centre Experience

Introduction: The Transfusion Unit of International Islamic University Medical Centre (IIUM MC) performs screening for red cell antibodies for all patients who are to be or might be transfused with red cell components. There are two types of red cell antibodies, the alloantibodies and autoantibodies. While the red cell autoantibodies are produced against self-antigen, the alloantibodies are the results of sensitization through transfusion or pregnancies. These antibodies are implicated in haemolytic transfusion reactions. This retrospective study examines the prevalence of red cell antibodies among patients of IIUM MC. Materials and Methods: All group cross matching and group screen and hold testing performed in IIUM MC from January 2017 to June 2018 were reviewed. Results: In total, samples of 3,712 patients were subjected to antibody screening using gel card. Twelve patients (0.32%) had positive antibody screening tests. The age ranged from 17 to 77 years. Nine (75%) patients were females. Four patients had positivity with Screening Cell I, one patient with Screening Cell II and III respectively. In the remaining patients (6/12) the antibody screening was positive for both Screening Cell I and II. In nine patients (0.24%) alloantibodies were identified, with six exhibiting multiple antibodies. The alloantibodies identified include anti-Le(a), anti-Le(b), anti-Kp(a), anti-C, anti-c, anti-E and anti-e. In three patients autoantibodies with no specificities were detected. Conclusion: Although the prevalence of red cell antibodies, specifically the alloantibodies is lower compared to other studies, the finding further reiterates the need to screen for unexpected red cell antibodies prior to red cell transfusion.

Frequency of unexpected red blood cell antibodies in Nanjing

Frequency of unexpected red blood cell antibodies in Nanjing

Incidence of unexpected red blood cell antibodies in the north of China

Incidence of unexpected red blood cell antibodies in the north of China

Analysis of Unexpected Antibodies Detected in Children: A Single Center Study for 7 Years

Frequency and distribution of unexpected red cell antibodies vary according to study population and method of antibody detection. The frequency and specificities of unexpected red cell antibodies were analyzed and compared in adults and children.

The Frequency and Distribution of Unexpected Red Cell Antibodies and Analysis of Antigen Exposure

The Frequency and Distribution of Unexpected Red Cell Antibodies and Analysis of Antigen Exposure

Seroprevalence of unexpected red blood cell antibodies among pregnant women in Uganda

Abstract We conducted a population-based, cross-sectional study among pregnant women in Kampala, Uganda, to determine ABO and D blood types and to determine the percentage who have unexpected red blood cell (RBC) antibodies and their specificities. De-identified blood samples from routine testing of 1001 pregnant women at the Mulago Hospital antenatal clinics in Kampala were typed for ABO and D and screened for the presence of unexpected RBC antibodies with confirmation and subsequent antibody identification. Of the 1001 blood samples tested, 48.9 percent, 26.4 percent, 21.0 percent, and 3.8 percent tested positive for blood groups O, A, B, and AB, respectively. Of these samples, 23 (2.3%) were negative for D, and 55 (5.5%) showed initial reactivity with at least one screening RBC. The RBC antibody screen was repeated on these 55 samples, and antibody identification was performed at the Johns Hopkins Hospital Blood Bank in Baltimore, Maryland. Twenty-one of the 55 samples were confirmed to have evidence of agglutination. Nine of the 21 samples demonstrated the presence of clinically significant RBC antibodies with anti-S being the most common, 8 samples demonstrated the presence of benign or naturally occurring antibodies, and 4 had only inconclusive reactivity. This study revealed a relatively high frequency of D and a low frequency of demonstrable clinically significant alloantibodies that may cause hemolytic disease of the newborn or hemolytic transfusion reactions among pregnant women in Kampala, with anti-S being the most frequent antibody specificity. Immunohematology 2012;28:115–7.

Delayed Hemolytic Transfusion Reaction due to Anti-Jkb: Case Report Highlighting the Importance of Early Blood Bank Consultation and Literature Review

Delayed hemolytic transfusion reactions (DHTR) can be asymptomatic or mimic other conditions and may be misdiagnosed. Failure to recognize this entity could lead to inappropriate treatment and future transfusions reactions. Anti-JK a and anti-JK b are the most frequently encountered antibodies responsible for DHTR ac companied by intravascular hemolysis on rare occasions. The antibodies are often difficult to detect because of their transient nature and their frequent dosage effect. We report the case of a 40-year-old female with DHTR due to unexpected weakly reactive anti-JK b . The patient, with a medical history of hypertension, multiple transfusions, multiple abortions and vaginal bleeding due to uterine fibroids, presented to our emergency department complaining of back pain for four days and red-brown color urine for one day. Significant jaundice was noted on physical examination. Laboratory data showed low hemoglobin (Hb) (6.0g/dl) and increased creatinine (3.11 mg/dl). Differential diagnosis included hemolytic-uremic syndrome, hematuria caused by urinary tract calculi, and autoimmne hemolytic anemia. Significant hemolysis was observed in the patient’s blood sample. Further questioning elicited a recent blood transfusion seven days prior. Red cell antibody work-up at that time showed the presence of anti-K and anti-E. The patient was transfused 2 units of K and E antigen negative cross-match compatible packed red blood cells(PRBCs). Post-transfusion Hb was 8.8 g/dl and there were no signs of any immediate complication. Review of the recent history of blood transfusion and the current findings led to our strong suspicion of intravascular hemolysis. The patient was treated vigorously with fluids and intravenous diuretics. Stat tests subsequently confirmed the intravascular hemolysis. A ‘new’ request for blood transfusion was put on hold while an antibody workup was initiated. Red cell antibody work-up results confirmed the presence of anti-K and anti-E; the direct antiglobulin test (DAT) was negative. An eluate prepared from the patient’s red cells was non-reactive by indirect antiglobulin test. Additional samples were sent to a reference laboratory for further investigation of unexpected red cell antibodies. Results from the reference laboratory confirmed the anti-E and -K, and, in addition, a weak anti- JK b was identified in the plasma and eluate. Both of the prior transfused units were subsequently shown to be Jk(b+), adding further evidence that the anti- JK b is most likely the culprit of the DHTR. The patient was subsequently transfused with E-, K- and Jk(b-) PRBCs and her condition improved. This case emphasizes the central role of blood bank consultation for early treatment and diagnosis of DHTR and for the avoidance of incompatible blood component transfusion, thus minimizing the risks of morbidity and reduce the potential for mortality. It is our opinion that blood bankers should be consulted when patients have an acute drop in Hb following recent transfusions. Moreover, transfusion medicine should be part of medical school education and part of hospital grand round conferences, to raise clinicians’ awareness to improve recognition and reporting of DHTR so that timely diagnosis and treatment can be made.

Screening and Identification of Unexpected Red Cell Antibodies by Simultaneous LISS/Coombs and NaCl/Enzyme Gel Methods

We evaluated the clinical usefulness of simultaneous LISS/Coombs and NaCl/Enzyme testing using the gel method for screening and identification of unexpected antibodies in 15,014 samples. When unexpected antibodies were detected by either screening test, those antibodies were identified using both the LISS/Coombs and the NaCl/Enzyme gel test. The positive screening rates of the LISS/Coombs, NaCl/Enzyme, and combined tests (excluding 25 autoantibody cases) were 0.48%, 1.29%, and 1.39%, respectively. Among the 57 samples positive by both screening methods, the antibodies in 19.3% could be identified only by the NaCl/Enzyme method. Among the 137 samples positive only by NaCl/Enzyme screening, 74.5% showed positive results in antibody identification only by the NaCl/Enzyme test, although 7.3% were also positive in the LISS/Coombs test. The NaCl/Enzyme method thus showed about threefold higher detection rates than the LISS/Coombs method, especially in screening for Rh antibodies, and higher exact identification rates and discriminatory power for identifying mixed antibodies. Addition of the NaCl/Enzyme method to routine laboratory procedures may detect and identify considerable numbers of significant antibodies that might be missed if only the LISS/Coombs method is used.

Micro‐Column Affinity Test and Gel Test: Comparative Study of Two Techniques for Red Cell Antibody Screening

Abstract Background and Objectives: We describe the results of a comparative evaluation of a gel test (ID Micro Typing) and a micro‐column affinity test (MCAT, Cellbind Screen) for red cell antibody screening and identification under routine conditions. Materials and Methods: 3,000 serum samples of patients from the Mannheim University Hospital were tested in parallel by means of the gel test and the MCAT, using the low‐ionic‐strength‐saline indirect antiglobulin test and the protein G affinity technique, respectively. Test cells used were the same in all tests. In addition, we performed titration studies with all detected antibodies as well as with 59 frozen sera containing antibodies of known specificity. Results: A total of 154 antibodies (5.1%) were detected, 149 by gel test and 147 by MCAT. The overall sensitivity and specificity of the gel test was 96.8 and 96.5% and of the MCAT 95.5 and 97.2%. No significant differences between the gel test and MCAT were found when the titer scores of all 213 (fresh and frozen) antibodies were used to check the results. The mean scores for the gel test and the MCAT were 26.8 and 28.5, respectively. For anti‐Fya and anti‐Kell, a significantly higher titration score could be obtained in the MCAT, whereas anti‐Lua showed a significantly higher score with the gel test. Conclusion: For the screening of unexpected red blood cell antibodies, the MCAT is as sensitive as the gel indirect antiglobulin test. The sensitivity and specificity of the two systems are more or less the same although it seems that lgM antibodies are better detected by the gel test.

Micro–Column Affinity Test and Gel Test: Comparative Study of Two Techniques for Red Cell Antibody Screening

Background and Objectives: We describe the results of a comparative evaluation of a gel test (ID Micro Typing) and a micro–column affinity test (MCAT, Cellbind Screen) for red cell antibody screening and identification under routine conditions. Materials and Methods: 3,000 serum samples of patients from the Mannheim University Hospital were tested in parallel by means of the gel test and the MCAT, using the low–ionic–strength–saline indirect antiglobulin test and the protein G affinity technique, respectively. Test cells used were the same in all tests. In addition, we performed titration studies with all detected antibodies as well as with 59 frozen sera containing antibodies of known specificity. Results: A total of 154 antibodies (5.1%) were detected, 149 by gel test and 147 by MCAT. The overall sensitivity and specificity of the gel test was 96.8 and 96.5% and of the MCAT 95.5 and 97.2%. No significant differences between the gel test and MCAT were found when the titer scores of all 213 (fresh and frozen) antibodies were used to check the results. The mean scores for the gel test and the MCAT were 26.8 and 28.5, respectively. For anti–Fy^a and anti–Kell, a significantly higher titration score could be obtained in the MCAT, whereas anti–Lu^a showed a significantly higher score with the gel test. Conclusion: For the screening of unexpected red blood cell antibodies, the MCAT is as sensitive as the gel indirect antiglobulin test. The sensitivity and specificity of the two systems are more or less the same although it seems that IgM antibodies are better detected by the gel test.

Hemoglobin-Based Blood Substitutes in the Blood Bank

Chemically modified hemoglobin (Hgb) solutions are being developed for use as blood substitutes. These solutions will cause the serum to appear grossly hemolyzed and will persist in the circulation for up to 4 days. Blood banks may soon need to accept and test patient specimens containing such blood substitutes. To evaluate how routine testing will be affected, we added chemically modified Hgb or 5% albumin to previously tested patient serum specimens with anti-K,-E, -Fy a , and -Fy b activity as well as to specimens lacking unexpected red cell antibodies. The diluted specimens were tested using panels of reagent red blood cells. No discrepant results were identified. In addition, red blood cells previously found to be positive and negative by direct antiglobulin test (DAT) were incubated with equal parts of chemically modified Hgb solution or 5% albumin. Repeat DAT testing demonstrated no discrepancies. These studies suggest that the presence of limited amounts of stabilized Hgb will not interfere with routine tests performed in the blood bank.

Commentary: testing for unexpected red cell antibodies—two or three reagent red cell samples?

Commentary: testing for unexpected red cell antibodies—two or three reagent red cell samples?

A survey of management of blood donations with unexpected red cell antibodies

A survey of 19 large blood centers, each with an average annual collection of 158,889 units, was conducted to identify. current practices of management of red cell units that contain unexpected red cell antibodies. The routine antibody identification, distribution, and charge for such units varied widely among the 19 centers. In addition, although use of these units was low, costs were considerable. This survey can serve as a basis for other studies to arrive at cost-effective ways to manage such units.