Transfusion Compatibility Testing Research Articles

Red blood cell alloimmunization in transfused patients with hereditary hemorrhagic telangiectasia: A single centre retrospective study

BackgroundHereditary hemorrhagic telangiectasia (HHT) is a genetic blood vessel disorder which may lead to chronic bleeding and red blood cell (RBC) transfusions. Data on transfusion requirements and complications in HHT patients are sparse. Study Design and MethodsRetrospective chart review was conducted at St. Michael’s Hospital (SMH) in Toronto, Canada. All adults with a definite clinical diagnosis of HHT AND inpatient hospital visits between January 1, 2011 and December 31, 2020 AND had undergone transfusion compatibility testing at SMH, were identified. Data were abstracted from electronic medical records. Simple descriptive statistics were used to analyze data. Institutional Research Ethics Board approval was obtained. Results63 HHT patients underwent compatibility testing and were subsequently transfused at SMH. Median patient age at data abstraction was 70 years (Interquartile Range [IQR]: 18) and 35 (56 %) were female. RBC alloantibodies were found in 23 transfused patients (36.5 %) and were predominantly directed against Rh and Kell antigens: Anti-E (65 %), Anti-K (39 %) and Anti-c (22 %) were most common. Excluding an outlier who received 611 RBC units during the study period, the mean number of RBC units transfused per HHT patient at SMH was 22.1 units (Standard Deviation: 40.9, IQR: 17). Six (9.5 %) transfused patients experienced at least one transfusion reaction. ConclusionRBC alloimmunization rate was 36.5 % in our cohort of transfused HHT patients; this is much higher than described in the general population and another transfused HHT cohort. The most commonly observed alloantibodies were Rh and Kell, supporting our policy of prophylactic phenotypic matching for these antigens for all transfused patients with HHT.

Establishment and discussion of autoverification rules for transfusion compatibility testing.

To develop an automated verification workflow for transfusion compatibility testing (TCT) based on the AUTO10-A guidelines and blood group serology characteristics and to conduct a simulated validation of the test and subtest results by assessing the appropriateness of the autoverification rules. The accuracy of TCT results is a fundamental prerequisite for ensuring the safety of blood transfusions. However, the verification of these results still requires manual intervention. Five autoverification rules and their standards were determined: agglutination intensity, normal results, logical relationships, delta checks and interlaboratory test comparisons. The established categories and standards for the five rules were retrospectively validated using 13 506 samples (requests) that had been manually verified in our laboratory from January 2020 to June 2023. A total of 66 638 test items were involved in the autoverification, with 3844 items violating the verification rules, resulting in a pass rate of 96.10%. Considering individual test items, four tests had a pass rate of more than 90% in both the test item result table and the test subitem result table. However, there were significant differences in the pass rates between different tests. The same conclusion can be drawn when the unit is requests. The different standards set for the agglutination intensity and the delta check in the ABO typing testing subitems showed significant differences in pass rates. The incorporation of manually verified results into the automated verification simulation indicated that the five rules established in this study have good applicability, and appropriate standards can lead to reasonable pass rates.

The Interference of Monoclonal Anti-Cluster of Differentiation 47 on Transfusion Compatibility Testing

Hu5F9-G4 and AK117, novel cluster of differentiation 47 blockers, are used to treat solid tumors and hematoma. Because cluster of differentiation 47 is expressed on erythrocytes, treatment with monoclonal anti-cluster of differentiation 47 may interfere with the results of transfusion compatibility testing. This study analyzed the interference and treatment of Hu5F9-G4 and AK117 on transfusion compatibility testing. Saline and microcolumn gel methods were used to identify the blood types of the patients. To screen irregular antibodies, salt water, indirect antiglobulin test and polyamine methods were used. Various methods were used to identify antibodies, including saline, indirect antiglobulin test, polyamine and acid diffusion. This paper explores current methods for removing interference caused by monoclonal anti-cluster of differentiation 47. Hu5F9-G4 interferes with reverse typing of ABO blood groups, resulting in agglutination of all reagents used in antibody screening and identification. Patients’ erythrocyte acid dispersive fluid reacted positively with spectrum cells and erythrocytes treated with papain reacted positively with serum. In saline and coagulant amine media, AK117 did not agglutinate with screening cells, but it did with antihuman globulin media. Pre-transfusion testing can be interfered with by anti-cluster of differentiation 47 antibodies. To ensure safe blood transfusions, patients should have their blood type tested and antibodies screened before treatment.

Effect of clinical application of anti-CD38 and anti-CD47 monoclonal antibodies on blood group detection and transfusion therapy and treatment

BackgroundTo investigate the effect of anti-CD38 monoclonal antibodies (mAb) (daratumumab, DARA) and anti-CD47 mAb combined with azacytidine on blood transfusion compatibility tests, transfusion effects in the treatment of multiple myeloma or acute myeloid leukemia and the corresponding management strategy. Materials and methodsAmong the 19 patients who were treated with DARA and anti-CD47 mAb, 4 patients with cross matching incompatibility were selected. The ABO blood group, the Rh blood group, irregular antibody screening and direct antiglobulin test (DAT) and cross matching testing were performed before and after the application of mAbs using serological methods. Then, irregular antibody screening and microcolumn gel cross matching tests were performed with donor and recipient erythrocytes and serum treated with DL-dithiothreitol (DTT) and Immucor kit, respectively. The transfusion effect was monitored. Results21.05% (4/19) patients had mismatched cross-matching results after mAb treatment. The agglutination intensity of irregular antibody screening tests (3 + ∼ 4 +) after anti-CD47 mAb was higher than that (1 + ∼ 2 +) after DARA. In the DARA group, treating RBCs with 0.2 mol L−1 DTT eliminated the DARA interference with antibody screening. In the anti-CD47 mAb group, the antibody screening, cross-matching test and DAT had been strongly interfered, and using Immucor kit eliminated the interference with antibody screening testing. There was no difference in the transfusion effect. ConclusionThe application of mAb drugs led to incompatibility of cross matching tests, and the transfusion effect was not affected.

Evaluation of Low Concentration Dithiothreitol for Negating the Monoclonal Anti-CD38 Interference with Transfusion Compatibility Testing

To investigate the effectiveness and safety of low concentration dithiothreitol (DTT) in removing the interference of monoclonal anti-CD38 on transfusion compatibility testing, and develop a reasonable clinical transfusion strategy. The blood type, direct antiglobulin testing (DAT) and antibody screening were tested according to standard methods. Antibody screening cells and donor's red blood cells were treated by DTT 0.2, 0.1, 0.05, 0.02, 0.01 and 0.005 mol/L, and antibody screening and cross-matching of serums after monoclonal anti-CD38 treatment were performed by anti-human globulin card. The 0.01 mol/L DTT at 37℃ for 30 minutes could remove the effect of monoclonal anti-CD38 on antibody screening and cross-matching, meanwhile retain their effectiveness in detecting anti-K, anti-LW, anti-JMH, anti-Lub, anti-e, anti-Dia and anti-Jka alloantibodies. All the 10 patients had no acute or delayed haemolytic transfusion reactions and their routine blood tests showed that the red blood cells transfusion was effective. The 0.01 mol/L DTT is a safe and effective method for removing the interference of monoclonal anti-CD38 with transfusion compatibility testing, while retaining the ability to detect most alloantibodies.

Pasteurized blood samples for transfusion compatibility testing during the coronavirus disease 2019 outbreak.

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Case series investigation on the Lewis system antibodies encountered during a routine screening in a tertiary care hospital-based blood center.

BACKGROUND:Anti-Lewis antibodies, usually do not react at 37°C, hence are clinically insignificant. However, on rare occasions, these antibodies have been reported as the cause for hemolytic transfusion reaction (HTR).AIM:We report our experience on the 6 cases of anti-Lewis antibodies that reacted at room temperature (RT) and at 37°C.MATERIALS AND METHODS:Standard serological methods were employed in detection and identification of antibodies. Demographic and clinical details were obtained from the records on the subjects under study.RESULTS:These were found among the patients and the blood donors of varied age groups and gender (21 to 65 years). Also, they were found among the patients with varied clinical diagnosis. The 2 patients in second trimester had anti-Le a or anti-Le b and other 2 male patients had anti-Le ab or anti-Le b with wide thermal amplitude were found during the course of pre- transfusion compatibility tests including antibody screening and cross-matching. Two male donors typed Le (a−b−) had anti-Le ab with wide thermal amplitude. Lewis antigen negative RBC units were provided for transfusion in the situation.CONCLUSION:Although antibodies to Lewis blood group antigens often react at lower temperatures and therefore remain clinically insignificant, some of them, on rare circumstances, may react at higher temperature of 37°C and may produce hemolytic episode or at least yield reduce survival of incompatible red cells in transfusion recipients. On safer side, the antigen-negative unit may be used in transfusion. The donors' registry with detailed phenotype profile may go a long way to provide blood for transfusion in emergency situations.

PS1594 EXPERIENCE WITH THE NEUTRALIZING AGENT DARAEX® IN BLOOD COMPATIBILITY TESTS IN PATIENTS TREATED WITH DARATUMUMAB

Background:Daratumumab is a human monoclonal antibody used for the treatment of multiple myeloma, which binds to CD38, a protein that is expressed on red blood cells (RBCs). Therefore, the plasma of these patients reacts with the RBCs producing a panreactivity and interfering in the transfusion compatibility testing. Panagglutination may persist for up to 6 months after the last infusion of daratumumab. An anti‐CD38 antibody for treatment of multiple myeloma shows a strong interference in the indirect antiglobulin test (IAT) where most of the reactions turn to unspecifically (wrong) positive. The time consuming standard technique using Dithiothreitol (DTT) counteracts the interference but has major drawbacks like destruction of Kel antigens or hemolysis. The DaraEx® compound inhibits the agglutination effect of anti‐CD38 in IAT without side effects. DaraEx® is a neutralizing agent for the inhibition of the agglutination effect of the anti‐CD38 antibody daratumumab in IAT.Aims:To validate the procedure to resolve the interference of daratumumab in transfusion compatibility testing using red cells treated with DaraEx® for the inhibition of the agglutination effect of the anti‐CD38 antibody daratumumab in IAT. Daratumumab can interfere with crossmatching and antibody screening in the IAT, which will allow us to identify a clinically significant antibody that has been initially masked by the presence of daratumumab.Methods:The study has been conducted in 25 plasma samples of patients diagnosed with multiple myeloma who have been treated with daratumumab. Irregular antibody screening tests and CrossMatching were performed on all of them, being positive in all cases. We performed the technique to eliminate reactivity by treating the red cells used in compatibility tests with DaraEx®, which neutralizes CD38 on the surface of the erythrocyte, thereby preventing Daratumumab from binding and inducing agglutination. The material used was DaraEx®, 0.9% NaCl LISS/Coombs ID‐Cards and Test cell reagents for the ID‐System; We performed the method in Biovue Column Agglutination Technology and gel card systems.Results:After performing the technique, we were able to eliminate panreactivity in both Irregular antibody screening tests and CrossMatching.Summary/Conclusion:Daratumumab causes panreactivity in vitro by binding to CD38 on reagent RBCs. It is necessary to do a baseline antibody screen (type and screen) before starting the treatment with daratumumab. Treating reagent RBCs with DaraEx® is a useful easy and quick method to mitigate the interference created by antiCD38 mAbs in pretransfusion testing. DaraEx is a quick and simple procedure; it doesn’t affect other antigens or alloantibody reactions. It doesn’t have side effects like destruction of blood group antigens or hemolysis as described for the standard DTT treatment. Therefore, we consider it a very useful technique to resolve interferences produced by daratumumb with blood compatibility testing. We believe that it is essential to have a validated technique to resolve these discrepancies. If an emergency transfusion is required, noncrossmatched, ABO/RhD‐compatible RBCs can be given, per local blood bank practices.

New mAb therapies in multiple myeloma: interference with blood transfusion compatibility testing.

Immunotherapeutic strategies are emerging as novel therapeutic approaches in multiple myeloma, with several mAbs being in advanced stages of clinical development. Of these, CD38 targeting antibodies appear very promising. In trials with anti-CD38 mAb daratumumab, all patients demonstrated panreactivity in red blood cell (RBC) panel testing, complicating the selection of compatible RBCs for transfusion. This review provides an overview of the interferences and solutions to safely transfuse these patients. CD38 is weakly expressed on human erythrocytes. Since the first reports on the interference, different solutions have been reported, including the neutralization of anti-CD38 mAbs in plasma by sCD38 or antiidiotype antibodies, CD38 depletion of RBCs using dithiothreitol or cord blood test cells, and transfusion of extensively typed RBCs. All methods have (dis)advantages, and it depends on the facilities of the immunohematology laboratory what strategy to choose. As the selection of suitable RBC units can be seriously delayed, hospitals should have protocols to communicate this interference with patients, laboratories, and physicians in a timely manner. As CD38 antibodies may also have a role in the treatment of diseases beyond hematological malignancies, chances are high that health professionals will encounter this issue in the nearby future.

Performance Assessment of Internal Quality Control (IQC) Products in Blood Transfusion Compatibility Testing in China.

Internal quality control (IQC) is a critical component of laboratory quality management, and IQC products can determine the reliability of testing results. In China, given the fact that most blood transfusion compatibility laboratories do not employ IQC products or do so minimally, there is a lack of uniform and standardized IQC methods. To explore the reliability of IQC products and methods, we studied 697 results from IQC samples in our laboratory from 2012 to 2014. The results showed that the sensitivity and specificity of the IQCs in anti-B testing were 100% and 99.7%, respectively. The sensitivity and specificity of the IQCs in forward blood typing, anti-A testing, irregular antibody screening, and cross-matching were all 100%. The reliability analysis indicated that 97% of anti-B testing results were at a 99% confidence level, and 99.9% of forward blood typing, anti-A testing, irregular antibody screening, and cross-matching results were at a 99% confidence level. Therefore, our IQC products and methods are highly sensitive, specific, and reliable. Our study paves the way for the establishment of a uniform and standardized IQC method for pre-transfusion compatibility testing in China and other parts of the world.

Passenger Lymphocyte Syndrome Following Solid Organ Transplantation: Graft Source, Incidence, Specificity, Duration, and Severity Of Hemolysis

BackgroundPassenger Lymphocyte Syndrome (PLS) is a rare complication of solid organ transplantation (SOT) and is marked by production of donor-derived antibodies towards host red blood cell (RBC) antigens. At Canada's largest SOT program, >400 transplants are conducted annually. The affiliated Transfusion Laboratory detects possible cases of PLS when previously seronegative hosts develop (delayed, non-transfusion-attributable) post-transplant antibodies (Ab) bearing unexpected, autoreactive (rather than alloreactive) RBC specificities. Donor attributability is established by discovery of the same specificity (on serologic lookback) and/or by the antithetical (seroconversion risk) phenotype. The incidence, duration, and severity of PLS remain unknown due to the infrequency of reported cases and the general absence of active surveillance. MethodBetween 1/10/2006 – 30/06/2013, PLS cases were discovered by the Blood Bank through pre-transfusion specimens. The specificities, phase (direct or indirect), correlative markers of hemolysis, and temporal profile of the Ab were subsequently followed according to patient and clinician interest. The severity of hemolysis (grade 0 to 5) at the time of nadir hemoglobin was judged according to the tiers defined by the Canadian Blood Services/IVIG Hemolysis Pharmacovigilance Group (CL#2011-34). Implicated organ and donor review (for relevant serology, and outcomes in any parallel organ distributions) were also attempted. ResultsOver 88 months, 2772 transplants occurred (992 kidney, 187 pancreas [with/after kidney in 113/74 respectively], 909 liver, 529 lung [437 double, 83 single, 9 +heart], 151 heart, 4 bowel). PLS was found in 14 or 0.5% (sex: 5F: 9M; mean age 56 years), with the implicated organ being lung or liver (9 [2%] and 5 [0.6%] respectively). All had a negative pre-transplant DAT with a pre-sensitized donor. PLS Ab specificities included ABO (8: 5A, 3B), RH (5 with ≥1 target [C:3, D:5, E:2, V:1]), and others (KIDD: Jka in 2; MNS: N in 1; unidentified in 1). Multiple Ab occurred in 5 (36%), usually within the same system (3 RH cases: C,D,E in 2; C,D,V in 1), but otherwise towards ABO + ≥1 target (B,Jka,N; B, unidentified). The time to the first detectable expression of an Ab (as signaled by a +DAT and/or screen) was 4-120 days (mean 24, median 15, n=14). Clinically significant hemolysis occurred in 11 (79%), with six grade 3 and five grade 4; the duration of hemolysis was 0-776 days (mean 148, median 38, n=11). The duration of Ab detectability (or the point of “last positivity”) was 12-851 days (mean 196, median 78, n=10), while the point of disappearance (“subsequent sustained negativity”) occurred between day 12-1288 (mean 298, median 45, n=10). Lookbacks were feasible with 5 implicated donors, and in only 1 case (of a contralateral lung's transplantation) was PLS detected in another recipient. PLS did not account directly for any deaths in the cohort, although hemolytic morbidity required treatment in 2 cases. Transfusion support with antigen-negative blood was provided to 11 patients for anemia that may have been due to hemolysis and/or other causes while the Ab was still evident. In one case, severe hemolysis provoked rate-uncontrolled atrial fibrillation with a supply and demand ischemia which culminated in irreversible congestive heart failure and cardiac death 2 months after PLS resolution. [Display omitted] Discussion/ConclusionsThis is the largest series of PLS reported to date. Clinician-driven submissions of blood for transfusion compatibility testing, and the discovery of discrepant serologies, represented an unforced but prospective means by which to identify PLS in roughly 1 in 200 transplants. Several cases transcended the limits of previously described temporal profiles (with the most delayed onset at 120 days, and the most prolonged duration at 2.3 years). The duration of hemolysis was consistently shorter than the duration of seropositivity, and was rarely life-threatening, while the most severe grades associated with RH rather than ABO or other targets. The surveillance achieved in this cohort revealed a longer-than-previously-appreciated duration of Ab productivity, and raised the question of whether or not such prolongation is a function of observation bias or the current-day armamentarium of anti-rejection therapeutics, which may be more permissive to donor-derived chimerism. Disclosures:No relevant conflicts of interest to declare.

Survey and analysis of testing capabilities of clinical transfusion laboratories in medical institutions in Beijing

Objective To investigate the testing capabilities of clinical transfusion laboratories in medical institutions in Beijing for the regulatory authorities to formulate administrative policies in this regard.Methods Experts assigned by Beijing Clinical Transfusion Quality Control Center made on-site inspections at the transfusion laboratories in medical institutions using quality control products.They recorded the complete testing process of the operators as well as the instruments,detection reagents in use and the testing results,with statistics and analysis made to the data so collected.Results The pass rate of these on-site inspections was lower than that of the external quality assessment.Some laboratories failed to complete the testing of the quality control products in time and the actual operations in some laboratories were inconsistent to the guidelines.55.9％ of level Ⅰ hospitals and 25.6％ of level Ⅱ hospitals were found with insufficient and inadequate instruments and process layout to meet the needs of clinical blood transfusion.Some of the technicians were found without sufficient trainings in their professional knowledge and basic skills,resulting in their poor competence against emergency cases and weakness in independent problem solving.In addition,the records of detection process and results were found to be substandard.Conclusions Transfusion laboratories in Beijing need to improve their testing capabilities in general. Key words: Transfusion compatibility testing; External quality assessment; Flight check; EQA quality control; Target value determination

Duffy genotyping facilitates transfusion therapy

The Duffy (FY) blood group system is clinically significant in transfusion medicine because FY antibodies are involved in hemolytic transfusion reactions and hemolytic disease of the newborn. The Fy(a) and Fy(b) antigens are encoded by the FY*A and FY*B alleles which are responsible for the Fy(a+b+), Fy(a+b-) and Fy(a-b+) phenotypes. The Fy(a-b-) phenotype is found in individuals homozygous for a silent FY*B allele, named FY*B ( ES ), which is caused by a mutation in the promoter region of FY*B that result in the loss of FY expression in the erythroid linage. The aim of the present study was to evaluate the role of FY DNA typing as a tool in transfusion compatibility testing. We studied 275 white blood donors from the city of Rosario by serological method and allele specific PCRs. We found that the 106 serologically Fy(a+b+) samples all genotyped as FY*A/FY*B (100%). Among the 94 Fy(a+b-) samples, 81 (86.2%) were FY*A/FY*A and 13 (13.8%) were FY*A/FY*B ( ES ) . Of the 75 Fy(a-b+) 67 (89.3%) were FY*B/FY*B and 8 (10.7%) were FY*B/FY*B ( ES ). No Fy(a-b-) samples were encountered. The frequencies of the FY*A, FY*B and FY*B ( ES ) alleles clearly revealed that the genetic pool analyzed is comprised of Caucasian and non-Caucasian alleles. These results showed that there is an important proportion of patients phenotyped as Fy(b-) that can be exposed to Fy(b+) blood units with no risk of alloimmunization when they carry the FY*A/FY*B ( ES ) genotype. Thus, FY genotyping allow increasing the pool of compatible units facilitating transfusion therapy and benefiting patients that require chronic transfusions.

貯血式自己血輸血の現状 日本輸血学会認定施設における検討 自己血輸血の採血，管理，実施状況について 輸血学会自己血輸血小委員会報告 １

In 1999, the Japan Society of Blood Transfusion organized a small committee on autologous blood transfusion. The committee was assigned to evaluate the status of predeposit autologous blood transfusion in hospitals approved by the Japan Society of Blood Transfusion and to clarify problems concerning the promotion of autologous blood transfusion. Questionnaires were sent to 86 hospitals. Information on each hospital (number of beds, number of doctors and medical technologists approved by the Society, etc), establishment of blood transfusion service, preservation methods, and management and compatibility testing of autologous blood were evaluated. In addition, number of cases and units of autologous blood transfusion from. Jan 1999 to Dec 1999 and status of homologous blood transfusion during operation were analyzed. Predeposit autologous blood transfusion was performed in all 68 hospitals which answered the questionnaire. Blood transfusion service was established in 64 hospitals. However, the place of autologous blood collection and the personnel involved in blood collection were not centralized. Percentage of autologous blood without allogeneic blood cases in cases of blood transfusion during operation was 17% in total. Percentages among hospitals ranged from 3.6% to 76.9%. Percentage of autologous blood units in units of blood used during operation was 12% in total, and ranging from 0.5% to 77.6%. Differences in the status of predeposit autologous blood transfusion were significant among hospitals. Doctors approved by the Japan Society of Blood Transfusion should assume an important role in the promotion of autologous blood transfusion in hospitals.

Transfusion Compatibility Tests

Transfusion Compatibility Tests

Transfusion Compatibility Tests

Transfusion Compatibility Tests

Transfusion Compatibility Tests

Transfusion Compatibility Tests

Transfusion Compatibility Tests

Transfusion Compatibility Tests

Transfusion Compatibility Tests

<h3>ABSTRACT</h3> Until 4 decades ago, the rates of stroke in low- and middle-income countries were considerably lower than those in more economically robust countries. In the intervening years, however, the rates of stroke in places such as southern India and rural South Africa have approximately doubled, whereas stroke rates in more economically developed nations have decreased. What is far more striking is that rates of disability and mortality arising from stroke are at least 10 times greater in medically underserved regions of the world compared with the most developed nations. The causes of these disparities are clear: above all, there is a lack of primary care treatment to screen patients for stroke risk and to mitigate risk factors. In addition, the lack of access to common drugs and basic medical equipment, as well as the lack of poststroke follow-up programs, rehabilitation, and secondary stroke prevention, means that individuals who would, in countries with better medical care, likely recover from stroke, instead have high rates of death and disability. Several global organizations, most notably the World Health Organization, have formulated and begun to implement public health programs to address these underserved regions. Their success depends on the support and expansion of these efforts so that short-term response to stroke, long-term stroke prevention and care, and screening and treatment of poststroke disabilities can be improved in underserved regions and the human and economic burden on these populations can be minimized.