Basophil activation test for allergic and febrile non-haemolytic transfusion reactions among paediatric patients with haematological or oncological disease.

BACKGROUND AND OBJECTIVES: Allergic transfusion reactions (ATRs) and febrile non-haemolytic transfusion reactions (FNHTRs) are common, although their mechanisms remain unclear. Immunoglobulin E (IgE)-mediated type I hypersensitivity may be involved in the pathogenesis of ATR. A basophil activation test (BAT) may help elucidate this process. MATERIALS AND METHODS: The BAT was based on peripheral blood samples from paediatric patients with a haematological or oncological disease and on samples of residual blood products transfused in each case. Dasatinib was used to evaluate whether basophil activation was mediated by an IgE-dependent pathway. RESULTS: Twenty-seven patients with and 19 patients without ATR/FNHTR were included in this study, respectively. The median BAT values associated with ATR- (n = 41) and FNHTR-causing (n = 5) blood products were 22.1% (range = 6.1%-77.0%) and 27.8% (range = 15.2%-47.8%), respectively, which were higher than the median value of 8.5% (range = 1.1%-40.9%) observed in blood products without a transfusion reaction. Dasatinib suppressed basophil activity. BAT values were comparable in patients with ATR regardless of severity. Meanwhile, BAT values analysed with blood products non-causal for ATR/FNHTR were higher in patients with ATR/FNHTR than in those without. CONCLUSION: The IgE-mediated type I hypersensitivity may be involved in the pathogenesis of ATR and FNHTR. BAT analyses may help elucidate the underlying mechanisms and identify patients at risk.

Pilot study on the use of basophil activation tests and skin tests for the prevention of allergic transfusion reactions.

Background and objectives: Management of severe allergic transfusion reactions (ATR) is challenging. In this study, we investigate the usefulness of skin tests and basophil activation tests (BAT) in chronically transfused patients for the prevention of future ATR. Materials and methods: BAT and skin tests were carried with the supernatant of red blood cell (RBC) units for a sickle-cell disease patient under chronic exchange transfusion who has presented a severe ATR, in order to prevent potential future ATR. If the results for both BAT and skin tests were negative, the RBC units could be transfused to the patient. If either one of the results was positive, the tested RBC unit was discarded for the patient. Results: 192 RBC units were tested with both tests. The level of results concordance between the two tests was 95%. Out of the 169 negative units with both tests, 118 units were transfused to the patient for which he presented no ATR. Conclusion: In our study, combining both BAT and skin tests was associated with a good negative predictive value since we were able to safely transfuse our patient. Further studies are still necessary to confirm this result but this pilot study indicates that skin tests and BAT might help prevent ATR. When BAT is not available, skin tests may also be useful in preventing ATR.

Detection of allergic transfusion-related adverse events from electronic medical records.

BACKGROUND: Transfusion-related adverse events can be unrecognized and unreported. As part of the US Food and Drug Administration's Center for Biologics Evaluation and Research Biologics Effectiveness and Safety initiative, we explored whether machine learning methods, such as natural language processing (NLP), can identify and report transfusion allergic reactions (ARs) from electronic health records (EHRs). STUDY DESIGN AND METHODS: In a 4-year period, all 146 reported transfusion ARs were pulled from a database of 86,764 transfusions in an academic health system, along with a random sample of 605 transfusions without reported ARs. Structured and unstructured EHR data were retrieved, including demographics, new symptoms, medications, and lab results. In unstructured data, evidence from clinicians' notes, test results, and prescriptions fields identified transfusion ARs, which were used to extract NLP features. Clinician reviews of selected validation cases assessed and confirmed model performance. RESULTS: Clinician reviews of selected validation cases yielded a sensitivity of 67.9% and a specificity of 97.5% at a threshold of 0.9, with a positive predictive value (PPV) of 84%, estimated to 4.5% when extrapolated to match transfusion AR incidence in the full transfusion dataset. A higher threshold achieved sensitivity of 43% with specificity/PPV of 100% in our validation set. Essential features predicting ARs were recognized transfusion reactions, administration of antihistamines or glucocorticoids, and skin symptoms (e.g., hives and itching). Removal of NLP features decreased model performance. DISCUSSION: NLP algorithms can identify transfusion reactions from the EHR with a reasonable level of precision for subsequent clinician review and confirmation.

Dual preparation of plasma and platelet concentrates in platelet additive solution from platelet concentrates in plasma using a novel filtration system.

BACKGROUND AND OBJECTIVES: Platelet concentrates suspended in a platelet additive solution (PAS-PC) are associated with a reduction in allergic response and are suitable for preparing pathogen-inactivated PC. We aimed to develop an efficient platform for the dual preparation of PAS-PC and platelet-poor plasma. MATERIALS AND METHODS: PAS-PC was prepared in six steps by using a hollow-fibre system based on cross-flow filtration: priming, loading PC, loading PAS, collection of filtered liquid (flow-through) and collection of platelets by washing with PAS followed by washing with air. In this study, the efficacy of platelet and plasma protein recovery and characteristics of recovered PAS-PC and flow-through plasma were analysed in detail. RESULTS: Recoveries of platelet in PAS-PC and plasma protein in the flow-through were 95.4% ± 3.7% and 61.6% ± 5.0%, respectively. The residual plasma protein in PAS-PC was 34.1% ± 2.8%. Although the expression level of CD62P, a platelet activation marker, in recovered platelets was approximately 1.2-fold of that in original platelets, swirling patterns were well retained, and aggregation in PAS-PC was not visible. Agonist-induced aggregabilities, platelet morphology and hypotonic shock recovery were conserved. The patterns of plasma protein and lipoprotein in the flow-through were comparable with those in the original PCs. The multimeric pattern analysis of VWF remained unaltered. CONCLUSION: We propose a highly efficient preparation system that enables the simultaneous production of PAS-PC and platelet-poor plasma. It also achieves a high recovery of functionally well-retained platelets with very low activation.

Frequency and clinical characteristics of allergic transfusion reactions in children.

Allergic transfusion reactions (ATRs)are a common form of acute transfusion reaction. It was aimed to determine the clinical characteristics and frequency of ATRs in children. This study included children who were transfused with red cell concentrate (RCC), fresh-frozen plasma (FFP), platelet concentrates(PC), apheresis granulocyte, and cryoprecipitate.The patients' sociodemographic characteristics, the blood product that caused the reaction, the type and timing of the reaction, the patient's age at time of reaction and their diagnosis, follow-up period, and clinical data were recorded. A total of 89703 bags of blood products were transfused to 4193 children.Two hundred eleven acute transfusion-related reactions occurred in 157 (3.74%) patients.Of these, 125 reactions (59%) were allergic. ATR occurred in 125 of 89703 infusions (0.14%).The median age of patients was 9.99 years (IQR:4.67-14.38) and ATRs occurred at a median of 30 minutes into the transfusion. Eighteen (18%) of the patients also had a history of drug reaction.When the blood products that caused ATRs were examined, 43(34.5%) occurred with apheresis and single-donor PC, 37(29.6%) with FFP, 32 (25.6%) with RCC, 10(8%) with pooled PC, 2(1.6%) with cryoprecipitate, 1(0.8%) with apheresis granulocyte.Ninety-nine(79%) of the reactions were minor allergic reactions and 26(21%) were anaphylaxis.Compared to minor allergic reactions, the proportion of PCs was statistically higher in anaphylaxis(p=0.02). Patients receiving PC should be monitored more carefully during the first half hour of transfusion. In addition, approximately one-fifth of the patients who developed ATR also had a history of drug reaction. Patients with previous reactions to drugs may be more likely to have ATR.

Platelet concentrate and type II IL-1 receptor are risk factors for allergic transfusion reactions in children.

PURPOSE: Allergic transfusion reactions (ATRs) are immunological reactions after transfusion. Interleukin-1 (IL-1) is a critical regulator for human diseases. We performed this study to investigate the association of type II IL-1 decoy receptor (IL1R2) expression with ATRs in children. METHODS: Children received blood transfusions between January and December 2019 were included. The age, sex, number and type of blood transfusion, allergic history, and medical history were collected and statistically analyzed. The blood samples were collected from children with and without ATRs for detecting the relative expression IL1R2 mRNA. Logistics regression analysis was performed to identify the risk factors for ATRs in children. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive performance of risk factors. RESULTS: Totally, 28,840 transfusions in 20,230 children, with 236 ATRs (0.82%) in 117 patients (0.58%) were included. ATRs were common in children at the hematology-oncology department, in children received higher number of blood transfusions, and older children. Platelet concentrate induced a higher incidence of ATRs (3.31%) than red cell concentrate (0.22%, p < 0.0001). After the transfusion, IL1R2 mRNA level was higher in the blood samples in children with ATRs than those without ATRs (p < 0.0001). Logistics regression analysis indicated that platelet concentrate (95% CI 3.555, 293.782) and IL1R2 expression (95% CI 1.171 × 102, 1.494 × 104) were independent risk factors for ATRs in children. IL1R2 expression had high performance in predicting ATRs (AUC = 0.998, 100% sensitivity and 98.85% specificity). CONCLUSION: High IL1R2 expression level in children who received blood transfusions may predict the morbidity of ATR.

Clinical utility of the basophil activation test for analysis of allergic transfusion reactions: a pilot study.

BACKGROUND AND OBJECTIVES: In previous studies, we demonstrated that the basophil-activating effects of supernatants found in residual-transfused platelet concentrates (PC-SNs) on whole blood basophils in cases of allergic transfusion reactions (ATRs) could be assessed by the basophil activation test (BAT) in terms of allergen/IgE dependency. However, in these studies, the basophils were derived from third-party healthy volunteers. In this study, we performed BAT using patients' own blood basophils to analyse ATRs. MATERIALS AND METHODS: The BAT was performed in two cases of severe ATRs using residual PC-SNs and the patients' own basophils in the presence and absence of dasatinib, an inhibitor of IgE-mediated basophil activation. RESULTS: In both cases, PC-SNs exhibited basophil-activating activity against the patients' basophils, but not against basophils from third-party healthy volunteers. In addition, basophil activation was inhibited in the presence of dasatinib, indicating that the basophils were activated in an allergen/IgE-dependent manner. Of note, the basophils in Case 2, but not in Case 1, were activated by PC-SNs from some unrelated non-haemolytic transfusion reaction cases. CONCLUSION: This pilot study indicates that the BAT may be useful in clarifying the causal relationship between ATRs and transfused blood as well as in elucidating the mechanisms behind ATRs considering the allergen/IgE-dependent pathway.

Allergic transfusion reaction caused by the shrimp allergen of donor blood: a case report.

OBJECTIVE: The purpose of this report is to analyze the cause of allergic transfusion reaction. METHODS: The methods of immunoblot and immunonephelometry were applied to detect the levels of the immunoglobulins of IgA (Immunoglobulin A) and IgE (Immunoglobulin E) and the level of sIgE (specific Immunoglobulin E) to shrimp allergen both in the patient's pre and post transfusion blood samples, respectively. RESULTS: After transfusion, The level of sIgE to shrimp showed "increase" corresponding to the concentration of 0.70-3.5 IU/ml. CONCLUSION: The allergic transfusion reaction was very likely caused by passive transfer of shrimp antigen to the patient allergic to shrimp.

Blood transfusion among thalassemia patients: A single Egyptian center experience.

BACKGROUND: Although red cell transfusions are lifesavers for patients with thalassemia, they are responsible for a series of complications and expose the patients to a variety of risks. MATERIAL AND METHODS: This cross-sectional study included 464 Egyptian beta(ß) thalassemia major patients whose age ranged between 10 months and 31 years (mean 10.2 ± 6.6 years). All patients were subjected to thorough history taking with special emphasis on blood transfusions regarding rate of blood transfusion, type of received blood, and history of previous transfusion reactions in addition to type of chelation and compliance to iron chelation therapy and history of diabetes. Serum ferritin and pretransfusion hemoglobin assessment were done for all patients. RESULTS: The mean pretransfusion hemoglobin level was 5.7 ± 1.16 g/dl. Allergic reactions were observed in 3.9% of the patients during the period of the study, while the history of previous allergic reaction was given by 72% of the patients. Deferiprone showed better compliance (58.6%) than deferoxamine (26.3%). The prevalence of diabetes was 10.1% among the studied group. On comparing diabetics to nondiabetics, serum ferritin, transfusion intervals, and age were statistically higher among diabetics (P<0.001). CONCLUSION: Lower pretransfusion hemoglobin and high rate of prevalence of diabetes, in addition to better compliance to deferiprone than deferoxamine, were detected among the patients.