Anaphylactic Transfusion Reactions Research Articles

Selective IgA Deficiency and Blood Component Transfusion: In Search of the Lost Evidence

Background: Selective IgA deficiency (IgA-D) has been historically considered a high-risk entity for developing allergic/anaphylactic reactions after blood transfusion (AATRs). However, it has been suggested that the IgA-D-related anaphylactic transfusion reaction is not evidence-based. Methods: We conducted three different approaches to collect evidence about epidemiology, AATRs, and transfusion management of patients with IgA-D at La Fe University Hospital. Firstly, we analysed the prevalence of IgA-D in a population of patients diagnosed with acute leukaemia, The second approach consisted of collecting transfusion data from IgA-D patients. Finally, we reviewed the IgA levels of patients recorded in the hemovigilance system suffering an AATR. Results: IgA-D prevalence was 1 in 334 patients. At least one blood component was transfused to 23 patients diagnosed with IgA-D. Plasma was transfused to eight IgA-D patients, while six patients received red blood cells, platelets, and plasma. No adverse reactions were reported in any patient. AATRs occurred in 325 men and 264 women with a median age of 52 years. Severe reactions occurred in 56 patients (1/14,520 components). Mean IgA levels were 215 mg/dL (4–5570) for mild reactions and 214 mg/dL (14–824) for severe reactions (p = ns). Washed platelets were administered to two patients who developed severe and repeated AATRs. Both had normal IgA levels. Conclusions: Since the AATRs related to IgA-D are extremely low, as reported in current hemovigilance systems, IgA-D should not be considered a high-risk entity to develop AATRs. On the contrary, our findings support standard transfusion management of IgA-D patients.

Guideline on the investigation and management of acute transfusion reactions.

Guideline on the investigation and management of acute transfusion reactions.

An Outbreak of Anaphylactic Transfusion Reactions to Group B Plasma and Platelets and its possible relationship to Alpha-Gal Syndrome

An Outbreak of Anaphylactic Transfusion Reactions to Group B Plasma and Platelets and its possible relationship to Alpha-Gal Syndrome

Atypical presentation of IgA-related immediate reaction with back pain and relative hypotension – anaphylaxis or not?

Anaphylactic transfusion reactions are rare occurring in approximately 1 in 50,000 red cell transfusions.1 One aetiology includes the development of antibodies against transfused IgA in patients with severe IgA deficiency. Diagnosis of IgA-related anaphylaxis involves the measurement of IgA levels and anti-IgA antibodies.2 Recently, the evidence underlying this entity and the causal relationship between laboratory tests and clinical manifestation has been questioned.3 We describe a case of a 50-year-old man with chronic anaemia with an infected enterocutaneous fistula.

Atypical presentation of iga-related immediate reaction with back pain and relative hypotension – Anaphylaxis or not?

Anaphylactic transfusion reactions are rare, occurring in approximately 1 in 50,000 red cell transfusions.1 One aetiology includes the development of antibodies against transfused IgA in patients with severe IgA deficiency. Diagnosis of IgA-related anaphylaxis involves the measurement of IgA levels and anti-IgA antibodies.2 Recently, the evidence underlying this entity and the causal relationship between laboratory tests and clinical manifestation has been questioned.3 We describe a case of a 50-year-old man with chronic anaemia with an infected enterocutaneous fistula. He received six red cell transfusions where he developed severe back pain and relative hypotension within 15–30 minutes of transfusion, settling after transfusion was ceased. He was afebrile with no respiratory, dermatological or gastrointestinal manifestations typical of anaphylaxis. Direct antiglobulin test was negative, and blood cultures were sterile. Tryptase taken 2.6 hours after symptom onset was raised 16 μg/L (0.0–11.4 μg/L). IgA level was <0.10 g/L (0.80–4.40g/L). Anti-IgA titre was 400 U/mL (0–7 U/mL). IgA deficient components were prepared pre-operatively. He subsequently received three washed red cells uneventfully, one during a laparotomy for the enterocutaneous fistula. This case describes an atypical presentation of a rare but important complication of blood transfusion, as well as the diagnostic process and subsequent management.

Complication Profile Associated With S1 Pedicle Subtraction Osteotomy Compared to Other Spinal Levels

Abstract INTRODUCTION S1 pedicle subtraction osteotomy (PSO) is rarely indicated. Therefore, its complication profile is not well defined. This study compares complication rates following S1 PSO to PSO performed at other spinal levels. METHODS A retrospective study of a consecutive cohort of adult spinal deformity (ASD) patients who underwent thoracolumbar 3 column osteotomy (3CO) by the senior author from 2006 to 2018 was performed. Multivariate analysis was used to asses complication risk stratified by osteotomy level. RESULTS A total of 363 patients underwent 3CO: 54 lower thoracic, 305 lumbar, and 6 S1. The number of lumbar PSO by level are as fsollows: L1 (24), L2 (26), L3 (135), L4 (102), and L5 (16). The indications for S1 PSO in this series were: high grade spondylolisthesis (spondyloptosis) in 4 cases and sacral fracture in 2 cases. Overall complication rate was 27.5%. Surgical and neurologic complications occurred in 7.7% and 5.8% of cases, respectively. Complication rate by 3CO level are as follows: thoracic (31.5%), L1 (29.2%), L2 (34.6%), L3 (20.7%), L4 (32.4%), L5 (12.5%), and S1 (50.0%). Relative to the thoracic level, S1 PSO was independently associated higher complication with an increase odd ratio of 39.60 (CI 3.12-503.41, P = .005). For S1 PSO, surgical and neurological complication rate was 16.7% for both outcomes; there was no significant difference between the 3CO levels. Specific complications encountered was a case of atrial flutter causing diastolic heart failure, a case of anaphylactic transfusion reaction, and a case with L5 weakness requiring hematoma evacuation and reduction of correction. One patient (16.7%) required revision surgery secondary to pseudarthrosis. Mean follow-up was 35.7 mo. CONCLUSION S1 PSO is a formidable procedure and associated with significantly higher complication rates than PSO performed at other levels. However, the technique is feasible with experienced surgeons. Large multicenter studies are needed to investigate this further.

Safety of Caplacizumab for the Treatment of Patients with Acquired Thrombotic Thrombocytopenic Purpura - Results Normalized to Time of Exposure in a Double-Blind, Placebo-Controlled, Phase 3 Hercules Study

Safety of Caplacizumab for the Treatment of Patients with Acquired Thrombotic Thrombocytopenic Purpura - Results Normalized to Time of Exposure in a Double-Blind, Placebo-Controlled, Phase 3 Hercules Study

Analysis of 81 cases with clinical adverse transfusion reaction

Objective To reduce the probability of adverse transfusion reaction and ensure the safety of transfusion according review the clinical cases. Methods The record of adverse transfusion reaction was retropectivly analyzed. Results 81 cases were occured adverse reactions caused by transfusion in 38 490 cases of our hospital, with the rate of 0.21%, including 52 cases of anaphylactic transfusion reaction and 29 cases of febrile non-hemolytic transfusion reaction.There wasn't statistically significant difference among of those blood components(χ2=3.849,P>0.05). Conclusion We should renovate the scientific and reasonable concept of blood transfusion, encourage autologous transfusion, strictly abide by the lows and regulations realated to transfusion, the probability of adverse transfusion reaction would be reduced. Key words: Adverse transfusion reaction; Anaphylactic transfusion reaction; FNHTR

Presence of medication taken by blood donors in plasma for transfusion.

The TRIP national hemovigilance and biovigilance office receives reports on side-effects and incidents associated with transfusion of labile blood products. Anaphylactic reactions accounted for the largest number of serious transfusion reactions in the period 2008-2012. In most cases, no cause is found for these reactions. TRIP data show that anaphylactic reactions occur relatively frequently with transfusion of plasma or platelet concentrates. Data from blood services show that 10% or more of plasma donors regularly use medication which is permitted under donation guidelines. It is conceivable that medication taken by the donor in plasma for transfusion could cause an anaphylactic transfusion reaction in the recipient. This exploratory study investigated the presence of drugs or drug metabolites in donor plasma. Samples (5ml) were taken from thawed, quarantine fresh frozen plasma units (FFP) which had to be rejected for transfusion because of leaks or length of time after thawing. The samples were analysed for approximately 1000 drugs and drug metabolites using a toxicological screening method. Eighty-seven samples were analysed. Toxicological screening was positive in fourteen samples (16%). In eleven samples, one substance was found, and in three samples, the presence of two or three drugs was detected. After freezing, storage and thawing of fresh FFP, it is possible to detect medication taken by the donor. Further investigation is recommended to analyse whether donors' medication in plasma can be implicated in some cases of allergic or anaphylactic reactions in transfusion recipients.

The entity of immunoglobulin A-related anaphylactic transfusion reactions is not evidence based.

The entity of immunoglobulin A-related anaphylactic transfusion reactions is not evidence based.

Antibody against immunoglobulin E contained in blood components as causative factor for anaphylactic transfusion reactions

Determining the mechanism underlying the development of transfusion reactions is important in transfusion therapy. Two bags of fresh-frozen plasma obtained from a donor (index donor) were implicated in two cases of anaphylactic transfusion reactions. The serum prepared from the index donor plasma transfused into the second patient (Patient 2) was evaluated using cord blood-derived mast cells (CBMCs) incubated with Patient 2 plasma. The component in the serum required for the degranulation was determined and quantified by chromatography in combination with degranulation assay, Western blot analysis, and enzyme-linked immunosorbent assay. The component in the plasma required for CBMC sensitization was determined using human immunoglobulin (Ig)E or normal plasma in place of Patient 2 plasma in the assay. Sera collected from the index donor between 2001 and 2008 were examined for the CBMC degranulation factor. The donor serum activated CBMCs incubated with Patient 2 plasma. The IgG fraction of the donor serum induced degranulation of CBMCs sensitized with IgE or plasma containing a normal IgE concentration. The IgG anti-IgE at a concentration higher than 2200 ng/mL, which showed CBMC degranulation activity, was detected in the donor sera for at least 7 years. Transfusion of a high concentration of the anti-IgE in the donor plasma was suggested to induce mast cell degranulation in the patients leading to the development of anaphylactic transfusion reactions. Antibodies existing in not only the patient circulation but also the transfused blood might cause transfusion-induced anaphylaxis.

Anaphylactic transfusion reaction in homozygous haptoglobin deficiency detected by CD203c expression on basophils

To the Editor: It has been reported that the incidence of anhaptoglobinemia who are homozygous for Hpdel is very rare in Africans or European-Africans. However, it is relatively high incidence in East Asian; 1/4,000 in Japan, 1/1,500 in Korea, and 1/1,000 in China 1. Some patients with anhaptoglobinemia develop anaphylactic or allergic transfusion reactions related to antihaptoglobin (Hp) antibodies 2. However, if anti-Hp IgE antibody is negative, it is difficult to elucidate an anaphylactic reaction. Flow cytometric basophil activating test (BAT) based on upregulation of the cell degradation/activation marker CD203c has been developed for monitoring the clinical course of patients with allergic diseases 3, 4. Here, we describe that BAT was a useful tool for diagnosing anaphylactic transfusion reaction associated with anti-Hp antibody. This case was an 8-year-old Japanese boy with acute lymphoblastic leukemia receiving intensive chemotherapy required transfusion. He was transfused with 14 units of leukocyte-reduced red cell concentrates (RCCs) and 150 units of leukocyte-reduced platelet concentrates for chemotherapy-induced anemia and thrombocytopenia without any transfusion-related reactions. However, immediately after starting the next infusion of RCCs, he developed dyspnea, urticaria, and hypotension. Screening tests for nonhemolytic transfusion reactions (NHTRs) were performed at the Japanese Red Cross. Serum analysis by nephelometry revealed Hp deficiency and their PCR method 1 showed complete absence of the Hp gene. He was diagnosed as having anhaptoglobinemia due to homozygous allelic Hpdel. Although anti-Hp IgG antibody was detected by ELISA and Western blotting, IgE antibody against Hp was not detected by ELISA or the IgE crosslinking-induced luciferase expression (EXiLE) test 5. To address the mechanism of this anaphylactic reaction, we performed BAT. As a control, a healthy adult and five age-matched children with severe egg allergy who had histories of food-induced anaphylaxis were examined. A commercial kit (Allergenicity Kit; Beckman Coulter, Fullerton, CA) was used for quantifying basophil CD203c expression 4. Upregulation of CD203c on basophils was determined using a threshold that was defined by the fluorescence of unstimulated cells and expressed as CD203c high % 6. CD203c high % was 23% for the patient and 4.38 ± 0.53% for the control, respectively (Table I). Haptoglobin induced enhancement of CD203c expression in the patient, but not in the control. Since basophils express high-affinity IgE receptors, it is reasonable to assume that the haptoblobin-induced basophil activation observed in the patient was mediated by haptoglobin-specific IgE bound to basophils. We did not detect antihaptoglobin IgE by the ELISA or EXiLE methods, but it is possible that the serum IgE concentration was too low to be detected, whereas the amount of cell-bound IgE was sufficient to induce anaphylaxis. Another possibility is that haptoglobin-specific IgG induced basophil activation. An IgG-mediated systemic anaphylactic reaction involving FcγRs, basophils, and platelet-activating factor was reported in a murine system 7, although it remains unclear whether such an IgG-mediated pathway also exists in humans. Our findings indicate that BAT may be useful for assessing the cause of NHTRs, especially anaphylactic reactions via high-affinity IgE receptors on basophils, leading to development of type I hypersensitivity response when no IgE can be detected in serum. The authors thank Yumi Tanaka, MSc (Blood Transfusion Service, Mie University Hospital) for kindly blood supplies. This work was supported by a Research Grant for Allergic Disease and Immunology (H20-015) from the Japanese Ministry of Health, Labor, and Welfare. Shotaro IwamotoMD, PHD, Takahiro YonekawaMD, Eiichi AzumaMD, PHD Pediatrics Unit, Mie University School of Medicine, Mie, Japan Takao FujisawaMD, PHD, Mizuho NagaoMD, PHD Clinical Research Unit, Mie National Hospital, Mie, Japan Eiko ShimadaMSC Central Blood Institute Unit, Blood Service Headquarters Japanese Red Cross Society, Tokyo, Japan Ryosuke NakamuraPHD, Reiko TeshimaPHD, Novel Foods and Immunochemistry Unit, National Institute of Health Sciences, Mie, Japan Kohshi OhishiMD, PHD Blood Transfusion Service Unit, Mie University Hospital, Mie, Japan Hidemi ToyodaMD, PHD, Yoshihiro KomadaMD, PHD Pediatrics Unit, Mie University School of Medicine, Mie, Japan

Detection of anti-IgA antibodies using the particle gel immunoassay: a rapid test for increased patient safety.

Patient safety is a major issue in transfusion medicine and commands continuous efforts to develop valid control methods aiming to avoid serious transfusion-related complications. Anti-IgA antibodies can cause anaphylactic transfusion reactions in IgA-deficient individuals. Since standard quantitative methods for anti-IgA measurement require considerable time to be performed, in an emergency situation it can be a challenge to prevent or to quickly interpret and manage acute transfusion reactions suspected to be a consequence of anti-IgA. The purpose of this study was to test and validate at our transfusion centre a rapid assay for the identification of patients with anti-IgA antibodies. Forty-six samples (6 from healthy controls and 40 from IgA-deficient patients) were collected. Sera were analysed blindly by three different clinical laboratory technologists using two DiaMed particle gel immunoassays (ID-PaGIA) for IgA deficiency and for antibodies to IgA. The results were subsequently checked with the results of a fluorescence enzyme immunoassay conducted in the reference immunology laboratory. The ID-PaGIA had a sensitivity of 91.7% and specificity of 97.1% for the IgA deficiency test. With regards to the detection of anti-IgA antibodies, the sensitivity was 89.3% and the specificity 100%. The reproducibility of the test was 100%. The ID-PaGIA screening assays are suitable for the investigation of transfusion-related anaphylactic reactions in a routine blood bank laboratory. Although the gel card technique does not quantify the level of anti-IgA antibodies, it is readily available, providing an effective and simple method for the diagnosis of anti-IgA related anaphylaxis and guidance for the appropriate transfusion practice in an emergency.

IgE- and IgG mediated severe anaphylactic platelet transfusion reaction in a known case of cerebral malaria

Background:Allergic reactions occur commonly in transfusion practice. However, severe anaphylactic reactions are rare; anti-IgA (IgA: Immunoglobulin A) in IgA-deficient patients is one of the well-illustrated and reported causes for such reactions. However, IgE-mediated hypersensitivity reaction through blood component transfusion may be caused in parasitic hyperimmunization for IgG and IgE antibodies.Case Report:We have evaluated here a severe anaphylactic transfusion reaction retrospectively in an 18year-old male, a known case of cerebral malaria, developed after platelet transfusions. The examination and investigations revealed classical signs and symptoms of anaphylaxis along with a significant rise in the serum IgE antibody level and IgG by hemagglutination method. Initial mild allergic reaction was followed by severe anaphylactic reaction after the second transfusion of platelets.Conclusion:Based on these results, screening of patients and donors with mild allergic reactions to IgE antibodies may help in understanding the pathogenesis as well as in planning for preventive desensitization and measures for safe transfusion.

Anaphylactic Transfusion Reaction in a Patient with Anhaptoglobinemia: The First Case in Korea

Anaphylactic transfusion reactions are rare complications of blood transfusions. Anhaptoglobinemia, a condition that has high incidence in Asia, can cause allergic transfusion reactions or anaphylaxis in severe cases. A 50-yr-old Korean woman was diagnosed with relapsed acute promyelocytic leukemia. She developed thrombocytopenia during chemotherapy and an anaphylactic transfusion reaction on the 4th and 5th platelet transfusions immediately after the transfusion of the platelet concentrates was initiated. Blood analysis showed no detectable serum haptoglobin. We examined her genetic phenotype and detected anhaptoglobinemia, which occurs because of an allelic deletion in the Hp gene cluster. The presence of an antibody against haptoglobin was detected by performing ELISA. To prevent anaphylactic reactions, apheresis platelets were transfused after washing. Consequently, anaphylactic transfusion reactions did not develop. Here, we report the first case of anhaptoglobinemia causing anaphylactic transfusion reaction in Korea.

Evaluation of particle gel immunoassays for the detection of severe immunoglobulin A deficiency and anti‐human immunoglobulin A antibodies

Immunoglobulin A (IgA)-deficient patients with anti-IgA (Ab) require transfusions using blood components with less than 0.05 mg IgA/dL as they are known to be safe for these patients. Identification of severely IgA-deficient (IgA SD) donors involved preliminary screening by the Ouchterlony double immunodiffusion assay followed by confirmatory testing at the required level of sensitivity for IgA and Ab at an external reference laboratory. Two in vitro particle gel immunoassays (ID-PaGIA IgA deficiency test and anti-IgA test) were also evaluated for their suitability in identifying IgA SD individuals and determining their Ab status. Samples from 198 donors and 36 patients, subjected to confirmatory testing for IgA SD and Ab over a 2-year period, were also evaluated using the ID-PaGIA kits. DiaMed test sensitivity and specificity for detection of IgA SD in donors was 98% whereas for Ab, test sensitivity was 91% at a specificity of 94%. In patients, sensitivity was 94% for IgA SD and 67% for Ab, both tests at a specificity of 100%. The ID-PaGIA IgA deficiency test was a sensitive and specific tool for identifying IgA SD donors or patients. Sensitivity of the Ab test was high for donors but reduced for patients and of high specificity in both groups. Further studies with patients are needed to confirm this latter observation. Implementation of these tests would make it possible to supply appropriate products from IgA SD donors to prevent anaphylactic transfusion reactions in patients.

Anaphylactic transfusion reactions

Anaphylactic transfusion reactions

Prevalence of immunoglobulin A deficiency in Chinese blood donors and evaluation of anaphylactic transfusion reaction risk

We investigated the incidence of immunoglobulin A (IgA) deficiency in Chinese population. The frequency of IgA deficiency, defined as a serum IgA level of <0.05 mg dL(-1) , has been broadly studied in different ethnic groups. Individuals with IgA deficiency may form specific antibodies against IgA, which can cause an anaphylactic response when the patient receives an IgA-containing blood transfusion. A sandwich enzyme-linked immunosorbent assay was performed to screen for IgA deficiency and particle gel immunoassay used for confirmation. IgA antibodies were further detected by the DiaMed anti-IgA test in IgA-deficient blood donors. Of the total 22,609 healthy blood donors screened, only seven cases were confirmed as having IgA deficiency (<0.05 mg dL(-1) ). Another seven cases displayed relative IgA deficiencies, with mean IgA concentrations ranging from 0.39 to 3.70 mg dL(-1) . Anti-IgA was identified in 2 of the 14 IgA-deficient blood donors whose IgA levels were <5 mg dL(-1) . Estimation of the theoretical risk for IgA anaphylactic transfusion reaction was 0.009%. The prevalence of IgA deficiency in Chinese is low. However, potential risks exist in performing blood transfusion to IgA-deficient persons, and measures should be taken to reduce IgA anaphylaxis.

Anaphylaxis from Passive Transfer of Peanut Allergen in a Blood Product

Anaphylactic transfusion reactions from passive transfer of IgE have been documented, but a case is now reported in which the eliciting factor was a food allergen in peanuts ingested by blood donors before donation.

In vitro quality of platelets during prolonged storage after washing with three platelet additive solutions

Patients with anaphylactic transfusion reactions require washed platelet concentrates (PCs) for subsequent platelet (PLT) transfusions. New PLT additive solutions (PASs) contain substances that might be beneficial for the preservation of PLT function during storage. This study compares the quality of PLTs washed and stored with T-Sol, Composol or SSP+. Fifteen buffy coats were pooled and divided into three parts. PCs with 30% plasma and 70% PAS (T-Sol, Composol or SSP+) were prepared. Washing was performed on day 5 of storage. Ten PCs were prepared and washed with each PAS. In vitro variables including haemostatic function (clotting time and clot retraction) were analysed on day 5 before, directly after and up to 2 days after washing. Swirling was well preserved, and pH was within acceptable limits (6·4-7·4) during storage for all PASs. The PLT number was reduced by washing for all PASs, and T-Sol PCs had a further decrease during storage. PLTs in T-Sol were spontaneously more activated and had lower capacity to respond to an agonist than Composol or SSP+ PLTs. The haemostatic function was only slightly changed by washing and during postwashing storage. PLTs washed with T-Sol, Composol or SSP+ had good in vitro quality for two days after washing despite absence of glucose. PLTs in T-Sol were more affected by the washing procedure and subsequent storage than Composol or SSP+ PLTs as judged by higher spontaneous activation.