Adverse Reactions In Recipients Research Articles

Reported side-effects following Oxford/AstraZeneca COVID-19 vaccine in the north-west province, Iran: A cross-sectional study.

While the vaccination was introduced as a promising tool to control the Coronavirus disease 2019 (COVID-19) pandemic, concerns about vaccine-related side effects had grown. Due to the widespread administration of the COVID-19 vaccine worldwide for the first time, it was necessary to evaluate the safety and potential side effects in recipients. This study aims to assess, the incidence of adverse effects following Oxford-AstraZeneca vaccination and identify their related factors. In this cross-sectional survey-based study, 453 volunteers participated, including 235 men and 218 women. The reported adverse reactions from recipients of the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine were collected by using a questionnaire. The findings showed that the incidence of adverse reactions, such as neurological, systematic, gastrointestinal, respiratory, and local symptoms were significantly higher after the first dose compared to the second dose. Systematic symptoms were the most prevalent reported side effects after the first and second dose injection. The demographical study of participants showed that individuals aged 18-34 and females were more prone to present adverse events following vaccination. However, no significant relationship was found between the occurrence of side effects and the recipients' body mass index. Despite the life-saving role of vaccination against SARS-CoV-2, it may have some adverse reactions in recipients. The severity and frequency of side effects were different. So, they were dependent on several factors, including gender and age. Altogether, post-vaccination adverse reactions were mild and tolerable.

Safety of plasma-derived blood products transfusions harvested from anti-SARS-CoV-2 positive and negative donors

Introduction. Testing for antibodies to the causative agent COVID-19 is not mandatory for donor blood or its components. It is unknown whether transfusion of plasma-containing blood components from seropositive donors is a safe procedure especially for immunocompromised hematological patients. Aim. To assess the frequency of adverse reactions and complications in hematological patients after transfusions of plasma-derived blood products harvested from anti-SARS-CoV-2 positive and negative donors. Material and Methods. 9152 transfusions of components harvested from anti-SARS-CoV-2 positive and negative donors were carried out from April 29, 2020 to January 21, 2022 at the NMRC for Hematology. Post-transfusion reactions and complications were analyzed in 576 hematological patients. 2059 plasma units, 327 cryosupernatant plasma units and 6766 cryoprecipitate doses were assessed. The occurrence of adverse reactions (hyperthermia) and complications within two hours after transfusion were evaluated. Results. Among 9152 blood units, anti-SARS-CoV-2 were detected in 2660 (29 %) cases and 6492 (71 %) were antibodies free. The analysis of adverse reactions and complications showed no significant differences in the incidence of adverse reactions in recipients after anti-SARS-CoV-2 positive and negative blood unit transfusions. Conclusion. There were no significant differences in the number of post-transfusion reactions when using donor blood components (fresh frozen plasma, cryosupernatant plasma, cryoprecipitate) obtained from donors in whose blood antibodies to SARS-CoV-2 were detected or not detected. Plasma-derived blood products from seropositive donors with a high degree of probability can be used to correct the plasma hemostasis path in hematological patients along with components prepared from seronegative donors.

Adverse Effects Reported and Insights Following Sinopharm COVID-19 Vaccination.

Vaccines are promising strategies for controlling COVID-19; however, COVID-19 vaccine side effects play a central role in public confidence in the vaccine and its uptake process. This study aimed to provide evidence on the post-vaccination early side effects of the BBIBP-CorV (Sinopharm) vaccine. This cross-sectional survey-based study was conducted between November 2021 and January 2022 among recipients of the BBIBP-CorV vaccine, using a questionnaire-based survey. Our final sample consisted of 657 participants, including 392 women. Among the study cases, only 103 (15.7%) participants received one dose of vaccine, and the rest received both doses (N = 554, 84.3%). Systemic symptoms (first dose: N = 187, both doses: N = 128) were the most commonly reported events after vaccination, and among them, injection site pain (first dose: 19.3%, both doses: 12.9%) was the most prevalent adverse effect. All reporting events were mild and resolved in less than 3days without hospitalization. Among the participants, females and young people aged 35-65 were more prone to manifest side effects (N = 169, 53.3%) after the vaccine injection. Furthermore, our results revealed that the recipients who were suffering from underlying diseases, including diabetes, renal disorder, and respiratory illness, reported fewer adverse responses after vaccination in comparison with healthy individuals. Vaccination against SARS-CoV-2 may lead to some adverse reactions in recipients. However, the frequency of post-vaccination early side effects differed in people, but all responses were slight and temporary.

Platelet and TRALI: From blood component to organism

Even though used systematically with leukocyte reduction, platelet transfusions still cause adverse reactions in recipients. They include Transfusion-Related Acute Lung Injury (TRALI), respiratory distress that occurs within six hours of the transfusion. The pathophysiology of this transfusion complication brings complex cellular communication into play. The role, particularly inflammatory, played by blood platelets in TRALI pathophysiology has been demonstrated, but is still under debate. Blood platelets play a role in inflammation, particularly via the CD40/CD40L (sCD40L) immunomodulator complex. In this study, we examine in particular the specific involvement of the CD40/CD40L (sCD40L) complex in the inflammatory pathogenesis of TRALI. This molecular complex could be a major target in a TRALI prevention strategy. Improving the conditions in which the platelet concentrates (PC) are prepared and stored would contribute to controlling partly the risks of non-immune TRALI.

Peculiarities of studying the effects of pathogen reduction technologies on platelets.

The transfusion of platelet concentrates (PCs) is mainly used for treatment of thrombocytopenic, trauma or surgery patients. The integrity and safety of these platelet preparations, however, is compromised by the presence of pathogens, such as viruses, bacteria and parasites. The transfer of allogeneic donor leukocytes contaminating PCs can also potentially cause adverse reactions in recipients. These considerations prompted the development and implementation of pathogen reduction technologies (PRT), which are based on chemically induced cross-linking and inactivation of nucleic acids. While the incumbent PRT may provide some protection against transfusion-transmitted infections, they are ineffective against infectious prions and may not inactivate other emerging pathogens. In addition, the safety of PRT concerning platelet viability and function has been questioned in several reports. Recent studies suggest that PRT, such as Intercept, may adversely affect the messenger RNA (mRNA) and microRNA content of platelets, as well as their functional integrity, which may compromise the clinical benefits of PRT. Here, we will discuss about the peculiarities of studying the effects of PRT on platelets, which will need to be taken into account in future studies aimed to characterize further, and polish, the rugged side of this otherwise useful and potentially important approach in transfusion medicine.

A summary of the Transfusion Error Surveillance System: 2008 - 2011.

Although Canada has one of the safest blood systems in the world, transfusion errors can occur at any time from the moment of collection through to the transfusion of blood and blood products. The Transfusion Error Surveillance System (TESS) was initiated by the Public Health Agency of Canada (the Agency) to monitor transfusion-related errors occurring at any point in the transfusion chain. To offer an analysis of the TESS data reported from 2008 to 2011. Between 2008 and 2011, 12 to 15 hospitals from four provinces participated in the TESS. Reports on all transfusion-related errors were sent electronically on a quarterly basis to the Agency where they were consolidated, cleaned, validated and analyzed. Different types of transfusion errors were categorized by time of discovery (pre- or post-transfusion) and their potential impact on the patient's health. The occurrence rates of different types of errors were calculated using corresponding denominator data. Results were grouped by the transfusion capacity of reporting hospitals. Between 2008 and 2011, a total of 34,088 transfusion-related errors were reported. Of these, 33,622 (98.6%) were detected prior to transfusion. The most commonly reported were errors related to the collection (40.1%) and handling (10.4%) of blood samples. Of the remaining 466 (1.4%) that were detected after transfusion, 66 were of high potential severity and 16 of them resulted in adverse reactions in recipients. Inappropriate / incorrect / no product order accounted for over 56% (n=9) of these errors and the most common adverse reaction was transfusion-associated circulatory overload which occurred in eight (50%) of the patients that developed adverse reactions. The TESS data from 2008 to 2011 demonstrates that blood transfusions are both safe and efficient in Canadian hospitals participating in the surveillance and also highlights the most common and most harmful errors that may be targeted for corrective actions.

Bacterial contamination of blood components: Norwegian strategies in identifying donors with higher risk of inducing septic transfusion reactions in recipients.

Bacterial contamination of blood and its cellular components remains the most common microbiological cause of transfusion associated morbidity and mortality, even in developed countries. This yet unresolved complication is seen more often in platelet transfusions, as platelet concentrates are stored at room temperature, in gas permeable containers with constant agitation, which support bacterial proliferation from relatively low undetectable levels, at the beginning of storage time, to relatively high virulent bacteria titers and endotoxin generation, at the end of shelf life. Accordingly, several combined strategies are introduced and implemented to at least reduce the potential risk of bacterial contaminated products for transfusion. These embody: improved donors arms cleaning; bacterial avoidance by diversion of the first portion of collection; reducing bacterial growth through development of newer storage media for longer platelet shelf life; bacterial load reduction by leucoreduction/viral inactivation, in some countries and eliminating the use potentially contaminated units through screening, through current available testing procedures, though none are not yet fully secure. We have not seen the same reduction in bacterial associated transfusion infections as we have observed for the sharp drop in transfusion associated transmission rates of HIV and hepatitis B and C. This great viral reduction is not only caused by the introduction of newer and more sensitive and specific detection methods for different viruses, but also the identification of donor risk groups through questionnaires and personal interviews. While search for more efficient methods for identifying potential blood donors with asymptomatic bacteremia, as well as a better way for detecting bacteria in stored blood components will be continuing, it is necessary to establish more standardized guidelines for the recognition the adverse reactions in recipients of potentially contaminated units. Efforts also should be also directed to identify blood donors with significant risk of bacteremia, at the time of donation in the first place as a high priority. The goal of this review is to highlights strategies for identifying both the sources of bacterial contamination of blood components in Norway and identifying donors with a higher risk of bacteremia at the time of donation. The key to achieving this goal is initiating continual revising and upgrading the Norwegian transfusion guidelines, based on the transfusion legislation and by introducing a relevant specialized donor bacterial questionnaire.

Assay of Pyrogens by Interleukin-6 Release from Monocytic Cell Lines

A novel in-vitro system has been developed for the detection and quantification of pyrogen in pharmaceutical products. The measured variable was evoked secretion of the pyrogenic cytokine interleukin-6 from MONO MAC 6 monocytic cells incubated with the product. The interleukin-6 was detected using a specific and sensitive ELISA developed for this purpose. The test system detected pyrogenic contamination in 3 batches of therapeutic human serum albumin which had caused adverse reactions in recipients. The contamination was not detected in conventional tests: the rabbit pyrogen test and the limulus amoebocyte lysate test.

Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation

During the transfusion of blood products, the transfer of allogeneic donor white blood cells (WBCs) can mediate adverse reactions in recipients. To minimize reactions, blood components are leukoreduced and/or exposed to gamma irradiation. Nucleic acid-targeted pathogen reduction technologies (PRTs) processes are well suited for WBC inactivation. The Mirasol PRT system (CaridianBCT Biotechnologies) uses riboflavin and ultraviolet light to reduce the active pathogen load and inactivate residual WBCs in blood products used for transfusion. The aim of this study was to compare the effect of PRT treatment to gamma irradiation. WBCs were resuspended in 100% plasma or in plasma containing 65% platelet additive solution (SSP+). A single product was split into three aliquots: control, PRT treatment, or gamma irradiation. After treatment, peripheral blood mononuclear cells were isolated from products, and cell viability and functionality were assessed in limiting dilution assays (LDAs), by CD69 expression, by proliferation, and by cytokine accumulation after lipopolysaccharide addition. PRT treatment and gamma irradiation reduced the ability of the T cells to proliferate by similar degrees as evidenced by a 6 log or greater reduction in the LDA and a lack of response to several stimuli. However, gamma-irradiated T cells were still capable of up regulating surface CD69, inducing a proliferative response in allogeneic responder cells, and producing levels of proinflammatory cytokines similar to those of untreated control cells, responses that PRT-treated T cells were incapable of mediating. These in vitro results demonstrate that PRT treatment is more effective than gamma irradiation at abrogating selected WBC immune functions.

Inactivated Split-Virion Seasonal Influenza Vaccine (Fluarix®)

Fluarix is a trivalent, inactivated, split-virion influenza vaccine containing 15 microg haemagglutinin from each of the three influenza virus strains (including an H1N1 influenza A virus subtype, an H3N2 influenza A virus subtype and an influenza B virus) that are expected to be circulating in the up-coming influenza season. Fluarix is highly immunogenic in healthy adults and elderly, and exceeds the criteria that make it acceptable for licensure in various regions (including the US and Europe). In a large, phase III, placebo-controlled, double-blind trial conducted in the US (2004/2005) in subjects aged 18-64 years, postvaccination seroconversion rates against the H1N1, H3N2 and B antigens were 60-78% and respective postvaccination seroprotection rates were 97-99% in Fluarix recipients. Another phase III trial conducted in the US (2005/2006) established the noninferiority of Fluarix versus another trivalent inactivated influenza virus vaccine in subjects aged >or=18 years, including a subgroup of elderly subjects. In annual European registration trials, Fluarix has consistently exceeded the immunogenicity criteria set by the EU Committee for Medicinal Products for Human Use for adults and the elderly. Fluarix demonstrated immunogenicity in small, open-label studies in at-risk subjects. During a year when the vaccine was well matched to the circulating strain, Fluarix demonstrated efficacy against culture-confirmed influenza A and/or B in a placebo-controlled trial in adults aged 18-64 years. In addition, Fluarix vaccination of pregnant women demonstrated efficacy in reducing the rate of laboratory-confirmed influenza in the infants and reducing febrile respiratory illnesses in the mothers and their new-born infants in a randomized trial. Fluarix was generally well tolerated in adults and the elderly in well designed clinical trials and in the annual European registration trials, with most local and general adverse events being transient and mild to moderate in intensity. The most common adverse reactions in recipients of Fluarix were pain, redness or swelling at the injection site, muscle aches, fatigue, headache and arthralgia. In conclusion, Fluarix is an important means of decreasing the impact of seasonal influenza viruses on adults and the elderly.

Pooled platelet concentrates: An alternative to single donor apheresis platelets?

Three types of platelet concentrates (PC) are compared: PC either processed with the platelet-rich plasma (PRP) or the Buffy coat (BC) method from whole blood units and PC obtained by apheresis. Leuko-reduction (LR) pre-storage is advocated to improve quality of the PC during storage and reduce adverse reactions in recipients. Standardization of methods allow preparation of PC with comparable yields of ∼400 × 10 9 platelets in pooled non-LR-PRP, ∼370 × 10 9 in pooled LR–BC–PC and in LR apheresis PC the number of platelets can be targeted on 350 × 10 9 or more with devices of various manufacturers. While viral transmission can be prevented by outstanding laboratory tests, the risk of bacterial contamination should be reduced by improved arm disinfection, deviation of the first 20–30 ml of blood and culture or rapid detection assays of the PC pre-issue. In a large prospective multicenter trial no significant difference was observed between cultures of apheresis PC ( n = 15,198): 0.09% confirmed positive units versus 0.06% in pooled BC–PC ( n = 37,045), respectively. Though platelet activation as measured by CD62 expression may differ in vitro in PC obtained with various apheresis equipment, and also between PC processed with the two whole blood methods there is scarce literature about the clinical impact of these findings. In conclusion the final products of LR–PC derived from whole blood or obtained by apheresis can be comparable, provided the critical steps of the processing method are identified and covered and the process is in control.

L’introduction de solutions de conservation dans les concentrés plaquettaires : vers une diminution des réactions transfusionnelles

Platelet concentrates (PC) are used in thrombocytopenia for curative or preventive treatment for hemorrhagic risk. Since five years, additive solutions have been added in PCs for several reasons; one of them is to present an interest in the intolerance in plasma reactions. The literature data have shown that these solutions entail fewer allergic reactions than PCs kept in plasma. This study was reviewed on three years of transfusion in France. The main objective of this study was to see if there was a difference in frequency when these PCs were in solution or not. All adverse reactions in recipients (ARR) occurring among PCs recipients (with and without additive solution) were analysed. The categories of ARR specifically studied were: allergies, febril non haemolytic reactions (FNHR) and the category “unknown”. This study shows that there is significantly lower incidence of allergies by introducing solution. For all ARRs, there is also a decrease in their frequency when PCs are in additive solution, it is significant except for the apheresis platelet concentrates. For categories FNHR and “unknown”, the results are opposed and/or not significant. This study confirms that introduction of additive solutions in PCs is able to reduce some allergic transfusion reactions.

Use of random versus apheresis platelet concentrates

The respective use of random (RPC) and apheresis (APC) platelet concentrates is highly heterogeneous among countries, ranging from 10 to 98% RPC in countries supposed to provide a similar transfusion service to patients. Moreover, when considering each country in the past 10 years, one can observe that some have changed their policy, switching from a majority of APC to RPC or vice versa. This presentation intends to analyse which factors may impact such decisions. For many years, the only available platelet component was a RPC obtained from whole blood donation by a two centrifugation steps process, the “platelet rich plasma” or PRP method. Since the beginning of the 1970s, APCs became available, with in fact many different techniques leading to many APCs that may not be equivalent. Since the end of the 1980s, a new method of RPC preparation was developed, using the buffy-coat (BC–PC), providing a blood component with highly preserved platelet functions as compared to RPCs prepared by the PRP technique. Finally, the use of each of these components either native, or leuco-reduced, or suspended in a storage solution, or processed with a pathogen inactivation technique adds new layers of complexity to compare them. Innumerable references can be found in the literature describing in vitro functional parameters of platelet concentrates. Although it is clear that BC–RPC retain much more their in vitro functions than PRP–RPC, indicating that no one should use the latter any more, it is much more difficult to distinguish differences between other PCs. Conversely, only a very few studies have been published related to a comparison of clinical efficacy of RPC versus APC, the endpoints being mainly CCI. Similarly to the in vitro studies, although RPC prepared with the PRP method show the lowest CCIs, no clear difference exists between “modern” RPC and APC. Another factor that may impact policy decision is the occurrence of adverse reactions in recipients. When considering only comparable data, for example leuco-reduced RPC versus leuco-reduced APC, there is now evidence that the latter is more associated with adverse reactions in recipients: data from hemovigilance in France show that, although no difference is noted for febrile non haemolytic transfusion reactions, nor for bacteria contamination, the incidence of allergic adverse reactions is about four times higher with APC as compared with RPC. Other aspects may impact the decision: the fact that using APC in place of RPC reduces the total donor exposure of patients was considered critical in some countries to reduce the risk of transmission of blood transmissible disease. Finally, the cost of the components, much higher for APC may be considered.

Past and Future Approaches to Assess the Quality of Platelets for Transfusion

No automated test exists to routinely measure platelet quality. Currently, the short, 5-day shelf life of platelet concentrates is largely dictated by the risk associated with bacterial contamination and not by platelet quality. With the implementation of bacterial testing and pathogen inactivation, platelet quality will become the major determinant for the shelf life of platelet concentrates. However, extended use of platelet concentrates stored beyond 5 days will require quality testing. In addition, high platelet quality would be expected to result in improved clinical efficacy, determined by count increment, improved hemostasis, and lower risk for adverse reactions in recipients. No in vitro quality test has yet demonstrated a good correlation with clinical efficacy or improved hemostasis. This review focuses on those tests of platelet quality that are based on platelet morphology. These include visual inspection of swirling, microscopic morphology score, measurement of light transmission through platelet concentrates, and platelet light scattering techniques. Recently, a new test for platelet quality has been introduced that uses dynamic light scattering. The advantages and remaining challenges for dynamic light scattering before it can become a routine platelet quality test are discussed.

Bacterial contamination of blood components

Despite considerable advances in the safety of blood components, transfusion associated bacterial infection (TABI) remains an unresolved problem. As yet there are no perfect preventative, screening and/or detection methodologies for eliminating contaminated units. Until a practical, rapid, cost-effective and logistically acceptable test becomes available, we should be satisfied with the choice of various limited solutions that at least partially improve the bacterial safety of blood components. It is also necessary to establish standardised guidelines and agreed upon systematic procedures for the recognition and reporting of the laboratory and clinical evaluation of adverse reactions in recipients of contaminated blood components.

Quality of platelet concentrates.

Despite the current emphasis in transfusion medicine on regulatory compliance and cost containment, there is continuing activity in quality improvement of blood products. Quality can be assessed by measuring both benefit and risk. High quality products are those in which the benefit is maximized and the risk minimized. Risk, in the context of platelet transfusions, is minimized by reducing infectious agents, sources of allergic reactions, and other factors likely to cause adverse reactions in recipients. Benefit can be better described as potency. Potency is the ability to produce a desired effect. For platelet concentrates, potency has both quantitative [platelet yield] and qualitative [platelet viability, survival, and function] components. There are many activities which may influence the potency of the final transfused platelet product and these are summarized in Figure 1. It is helpful to review each step in order to assess the potential impact on the potency of the final transfused product.