Haemolytic transfusion reactions caused by non-ABO red cell antibodies reported to the Norwegian Haemovigilance System 2004-2020.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyse the reports received in the Norwegian Haemovigilance System from 2004 to 2020 on acute and delayed haemolytic transfusion reactions caused by non-ABO red cell antibodies. MATERIALS AND METHODS: Antibody specificity, clinical symptoms and outcomes were included when available. RESULTS: After transfusion of 3.7 million red cell concentrates, reports on 78 cases of haemolytic transfusion reactions caused by non-ABO red cell antibodies were received, corresponding to an incidence of 1 in 47,000 transfused red cell concentrates. There were 30 acute and 48 delayed haemolytic transfusion reactions. A total of 113 red cell antibodies were found: 82 alloantibodies, 6 autoantibodies and 25 cases where the antibody specificity could not be determined. Two fatalities occurred: one caused by anti-Wra and one caused by an unidentified red cell antibody. The most frequently reported antibody specificities were those in the Rh and Kidd blood group systems, representing 24% and 14%, respectively, of all the antibodies identified. In six cases, errors occurred, leading to the issuing of blood units without the required phenotype match. CONCLUSIONS: Despite the possible underreporting, the low number of serious haemolytic transfusion reactions reflects an adequate pre-transfusion practice by the Norwegian blood banks.

COVID-19 patients treated with convalescent plasma. / Covid-19-pasienter behandlet med rekonvalesensplasma.

BACKGROUND: In Norway, treatment with COVID-19 convalescent plasma has been given through the NORPLASMA project. The treatment was initially offered to critically ill patients after an individual assessment, but from December 2020, the indication was limited to critically ill, immunocompromised patients. In this article we describe clinical characteristics, comorbidity and mortality in patients who received convalescent plasma in these two periods. MATERIAL AND METHOD: From 22 April 2020 to 30 March 2022, a total of 79 patients were included in the observational studies NORPLASMA MONITOR and the Norwegian SARS-CoV-2 study. The patients had received a total of 193 units of convalescent plasma at 15 Norwegian hospitals/nursing homes; 62 in South-Eastern Norway Regional Health Authority, 8 in Western Norway Regional Health Authority and 9 in Central Norway Regional Health Authority. Information on immune status, comorbidity and course of infection was retrieved from the patient records after informed written consent was obtained. RESULTS: Of 79 patients with a median age of 65 years (interquartile range 51-⁠73) who were treated with convalescent plasma, 31 (39 %) died during hospitalisation. A total of 59 patients were immunocompromised, and of these, 20 died in hospital compared to 11 of 20 who were assumed to be immunocompetent. Median number of comorbidities was 2 (interquartile range 1-4). The patients received a median of two plasma units (min.-max. 1-21). Two of the patients developed mild allergic skin reactions. INTERPRETATION: Convalescent plasma was well tolerated by patients with COVID-19. Immunocompromised patients may have benefitted from the treatment, with lower mortality than for those assumed to be immunocompetent.

Convalescent plasma from Norwegian blood donors to treat COVID-19. / Rekonvalesensplasma mot covid-19 fremstilt fra norske blodgivere.

BACKGROUND: At the start of the pandemic, the Norwegian Directorate of Health and Norwegian blood banks initiated the production of COVID-19 convalescent plasma within the framework of clinical studies. In this article we describe the blood donors who participated. MATERIAL AND METHOD: Blood donors who had recovered from COVID-19 were recruited to donate single donor plasma for the purpose of patient treatment. Data on the course of infection, leukocyte antibodies and antibody level against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) per plasma unit were registered after informed consent was obtained. We calculated a disease score defined as the total number of self-reported symptoms/findings and hospitalisation where relevant (score 0-⁠11). RESULTS: A total of 1644 plasma units were collected from 266 plasma donors at 12 blood banks. Median disease score was 5 (interquartile range 3-⁠6), and 15 donors had recovered from pneumonia and/or been hospitalised. A total of 599/1644 plasma units from 106/266 donors met our requirement for SARS-CoV-2 antibody content (> 60 % inhibition of virus binding to angiotensin-converting enzyme 2 (ACE2)) or positive virus neutralisation test. The antibody level in donors waned over time following infection, and showed no clear correlation with disease score. INTERPRETATION: The number of symptoms and findings in blood donors could not predict antibody response at individual level, and antibody testing was crucial for the production of effective convalescent plasma.

COVID-19 convalescent plasma: current status, lessons from the past and future perspectives.

When the COVID-19 pandemic hit, blood transfusion services worldwide started collection of convalescent plasma as early as possible, as exemplified by the response in Norway. There were challenges related to donor selection, donor safety, testing for relevant antibodies and indications for and dosing of the convalescent plasma. As more knowledge became available, the product quality was more standardised. Multiple case reports, observational studies and some randomized studies were published during the pandemic, as well as laboratory studies reporting different approaches to antibody testing. The results were conflicting and the importance of convalescent plasma was disputed. Even though there has been strong international collaboration with involvement of many key organisations, we may better prepare for the next pandemic. An even stronger, more formalised collaboration between these organisations could provide more clear evidence of the importance of convalescent plasma, based on the principles of passive immunisation.

COVID-19 convalescent plasma from Norwegian blood donors. / Covid-19-rekonvalesensplasma fra norske blodgivere.

The collection and use of convalescent plasma to treat COVID-19 has taught us important lessons about the organisation, testing and selection of blood donors and patients. This is knowledge that can be used in the next pandemic.

External quality assessment providers' services appear to more impact the immunohaematology performance of laboratories than national regulatory and economic conditions.

OBJECTIVES: Medical laboratories may, at their own discretion, exceed but not undercut regulatory quality requirements. Available economic resources, however, may drive or hinder eagerness to exceed minimum requirements. Depending on the respective scopes of regulatory and economic framework conditions, differing levels of quality efforts to safeguard laboratory performance can be anticipated. However, this has not yet been investigated. METHODS: Immunohaematology external quality assessment (EQA) results collected by 26 EQA providers from their participant laboratories in 73 countries from 2004 to 2019 were evaluated. Error rates were aggregated in groups according to the respective national regulatory and economic framework conditions, to whether or not expert advice was provided in case of incorrect results, and the frequency of EQA samples. RESULTS: These representative data indicate no association between national regulatory (mandatory participation in EQA, monitoring of performance of individual laboratories by authorities, financial consequences of incorrect results) and economic (level of national income, share of national health expenditure) conditions to the quality performance of medical laboratories in immunohaematology. However, EQA providers' support for laboratories in the event of incorrect results appear to be associated with lower error rates, but a high EQA sample frequency with higher error rates. CONCLUSIONS: Further research into the impact of introducing or changing services of EQA providers is needed to confirm the results found in this first of its kind study.

Transfusion practice at Sørlandet Hospital / Transfusjonspraksis i Sørlandet sykehus.

BACKGROUND: Norway has no overview of the number of patients who are transfused, their age and gender distribution or reasons for transfusion. We wished to investigate which patient groups received blood at Sørlandet Hospital in 2010-2011, and to test a method of electronic data linkage from treatment systems, with a view to further monitoring of blood consumption. MATERIAL AND METHOD: Data from all patients treated in somatic departments at Sørlandet Hospital in the period from 1 January 2010 to 31 December 2011 were linked to data from the blood bank with the aid of the system 'Forskning i sykehus'. SPSS version 23.0 was used for the statistical analyses. RESULTS: A total of 19 108 red blood cells and platelet concentrates were transfused to 3 967 patients, with the same number of units for both genders. Patients older than 60 years accounted for 79 % of the total blood consumption. Patients in the main diagnostic group neoplasms had the most transfusion episodes, followed by the diagnostic groups injuries, diseases of the digestive system and diseases of the blood. In cases of primary and secondary hip prostheses, 33.8 % and 65.6 % of the patients received blood, respectively. For caesarean section the figure was 8.9 %. INTERPRETATION: Our data are comparable to data from other countries. The method is suitable for assessing and monitoring transfusion practice. It could also be used by other health trusts and to collect national data after all blood components and parameters such as haemoglobin, blood group and transfusion complications are included.

Eight years with haemovigilance in Norway. What have we learnt?

The purpose of a haemovigilance system is to identify complications related to transfusion or blood donation, analyze them and learn in order to avoid complications in the future. The Norwegian Haemovigilance System (Troll) started as a voluntary, professionally led reporting system in 2004. In 2007 haemovigilance became an authority task, according to the EU blood directive, and reporting of serious adverse reactions and serious adverse events became mandatory. The Norwegian Directorate of Health became responsible for the system and asked The Norwegian Knowledge Centre for the Health Services to run it. Results from the first eight years of reporting are presented. A total of 2607 transfusion complications or incorrect blood component transfused (IBCT) have been reported (127 per 100,000 transfusions). Most transfusion reactions are mild. The most frequently reported are febrile non-hemolytic and mild allergic reactions. Serious adverse reactions such as anaphylaxis, TRALI and hemolytic transfusion reactions occur, but are rare. One incident of bacterial transmission and four incidents of viral transmission have been reported, among them one case of HCV transmission. No incidents of transmission of HIV or hepatitis B have been reported. IBCT was reported 168 times. Our data are comparable with data from other countries. Recommendations from the haemovigilance system are included in local and national guidelines. Increased knowledge of haemovigilance among physicians and nurses can lead to improved transfusion safety. It is safe to receive blood in Norway, but serious adverse reactions do occur. Our reporting system seems to be well accepted. We have not yet been able to document any change of practice that has lead to a reduction in the number of complications.

[Syphilis and blood transfusion]. / Syfilis og blodtransfusjon.

BACKGROUND: In 2007, previous syphilis infection was diagnosed in a blood donor who had given blood regularly for 15 years. This was discovered when the donor was tested for syphilis, as a new donor in another blood bank. The time of infection is unknown. An expert group, set up by The Norwegian Directorate of Health, was commissioned to evaluate the risk of syphilis transmission through blood products in Norway. MATERIAL AND METHODS: The expert group based its evaluation on the epidemiology of syphilis, risk of infection and properties of the syphilis bacterium, especially in relation to blood donation. Specific information about the actual incident, made available by the Norwegian Directorate of Health, was also evaluated. RESULTS: Of 54 blood recipients 21 were alive and 18 (86 %) were tested for syphilis, all with a negative result. For 11 deceased the hospital records were studied without discovering signs of syphilis infection. INTERPRETATION: The risk of transfusion-transmitted syphilis is low for several reasons: The prevalence of syphilis in the population is low, a compulsory interview and completion of a questionnaire before donation in Norway excludes patients who are ill or at risk of being infected; the proportion of fresh blood donations is very low and syphilis bacteria die quickly during normal storage conditions for blood. An incidental infection is symptomatic and easily treated by antibiotics. The expert group recommends to not start syphilis testing of each blood donor but to continue the present routine testing of new donors.

Indications for use and cost-effectiveness of pathogen-reduced ABO-universal plasma.

PURPOSE OF REVIEW: Donor selection and viral screening methods combined with pathogen reduction have increased the safety of pooled plasma to a level which makes reintroduction of ABO-universal plasma an important option. RECENT FINDINGS: Solvent detergent-treated pooled plasma has proved to be well suited for the production of pathogen-reduced ABO-universal plasma. One such product, Bioplasma FDP, was licensed in South Africa in 1994 and has since 1996 been in successful clinical use. A clinical study with this product and two studies with the European product, Uniplas, have confirmed the efficacy and safety of pathogen-reduced ABO-universal plasma. SUMMARY: Pooling of plasma enables the production of ABO-universal plasma. Pathogen reduction with solvent detergent eliminates lipid-enveloped viruses, whereas neutralizing antibodies in the plasma pool and nucleic acid amplification testing ensures the safety for recognized nonlipid-enveloped viruses. Pooling also eliminates transfusion-associated acute lung injury (the leading cause of plasma transfusion-related death), reduces immunologic/allergic adverse events by 60-80% and standardizes plasma protein content. Thus, in addition to ABO compatibility, pathogen-reduced ABO-universal plasma has important supplementary benefits that improve the product's cost-effectiveness.

[Overutilization of clinical biochemical analyses?]. / Overrekvirering av laboratorieanalyser i medisinsk biokjemi.

BACKGROUND: A pilot study was conducted in order to highlight the possibly unnecessary requisitioning of biochemical analyses in a Norwegian hospital. MATERIAL AND METHODS: The following parameters from consecutive patients and focusing repeated testing were included in the study: i) serum protein electrophoresis (30 patients), ii) thyroid function tests in serum (43 patients), iii) prothrombin time test (PT-INR) (30 patients), iv) haemoglobin (30 patients) and v) an analysis package of 13 single tests designed for the primary investigation of "acute abdomen" (30 patients). Criteria for correct and incorrect requisitioning were defined. RESULTS: 69% of the acute abdomen test package requisitions were incorrect, although single tests within the package may have been justified. 17% of PT-INR and 15% of haemoglobin tests were superfluous, while nearly all serum protein electrophoresis and thyroid analyses were not unnecessarily repeated. INTERPRETATION: The study demonstrated a clear possibility for reducing financial as well as labour costs by correct requisitioning of biochemical analyses, without loss to the quality of diagnostic service and treatment.

Microchimerism in immune competent patients related to the leukocyte content of transfused red blood cell concentrates.

BACKGROUND: Microchimerism may play a part in transfusion complications. The aim of this study was to examine whether establishment of post-transfusion microchimerism was related to leukocyte content. METHODS: Twenty non-pregnant female patients, without known malignant or immunological diseases, mean age 68 years, receiving 2-4 units of red blood cell concentrates during elective surgery, were included. One or two of the units were from male donors. Ten patients received buffy-coat depleted red blood cell concentrates, leukocyte count 108-109 per unit, and 10 patients received red blood cells leukoreduced by prestorage leukocyte filtration, with a leukocyte count of <106 per unit. EDTA samples were collected in vacuum tubes before and after 1 week and 6 months after transfusion. The tubes were frozen and stored at -400 degrees C. Genomic DNA was isolated and PCR performed using four primer sets amplifying markers on the Y-chromosome. RESULTS: Microchimerism was detected in a total of eight out of the 20 patients. In three patients microchimerism was detected only before transfusion. These patients had given birth to one or two boys each, and had no history of previous transfusion. Two patients receiving buffy-coat depleted red blood cell concentrates and two patients receiving leukoreduced red blood cell concentrates had detectable microchimerism 1 week after transfusion. The age of the transfused red blood cell concentrates was 6, 24, 8 and 7 days, respectively. One patient receiving leukoreduced red blood cell concentrates had detectable microchimerism after 6 months. The age of this concentrate was 22 days. DISCUSSION: This study demonstrates that microchimerism after transfusion does not seem to be dose dependent, and can be induced even by a >3 week old leukoreduced red blood cell concentrate with a very low leukocyte content.

Guidelines for transfusion in Norway.

The Norwegian guidelines for transfusion are harmonised in terms of standards with the European directives, but we have two areas where there are substantial differences. First, in Norway a blood donor is defined as a patient in legal terms. Secondly, we have stricter criteria for geographical origin of the people who are allowed to donate blood than most other countries. It is a challenge to provide information stating that these guidelines are related to the risk of transmitting infectious disease rather than discrimination. Increased focus on hemovigilance and closer contact between the blood banks and the national health authorities will be major issues in future work to improve the quality of Transfusion Medicine in Norway.

Donor lymphocytes transferred with the graft to kidney recipients. Potential for establishing microchimerism.

After solid organ transplantation donor lymphocytes have been shown to survive and multiply in the organ recipient for a prolonged period. It is not clear whether this chimerism detected is the result of immunosuppression or the cause of allograft acceptance. The number of cells transferred, as well as the type of cells, and the degree of activation are likely to be of importance for the establishment of microchimerism. The cells that are flushed out of the vascular tree may be of particular importance since when an antigen primarily bypasses or secondarily avoids organised lymphoid collections, the immune system in the recipient may remain or become "indifferent" to its presence. In the present study we examined the amount of residual donor blood cells that we could flush out from the vascular tree of living donor kidneys and cadaveric donor kidneys immediately prior to transplantation, with special emphasis on T and B lymphocytes. Our study shows that perfusion of donor kidneys just prior to transplantation releases from 0.1 to 1.8x10(6) B-lymphocytes, with an average of 0.7x10(6) and from 0.5x10(6) to 2.6x10(6) T-lymphocytes, with an average of 1.8x10(6), for CD kidneys, and somewhat less for LD kidneys. These cells would otherwise have been flushed out into the organ recipient's circulation, where they might play a role in the establishment of microchimerism.