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.

Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP.

OBJECTIVES: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA). METHODS: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "Autoimmunity Testing"; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP). RESULTS: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations. CONCLUSIONS: These recommendations are an important step to achieve high quality ANA testing.

Repository of intra- and inter-run variations of quantitative autoantibody assays: a European multicenter study.

OBJECTIVES: No reference data are available on repositories to measure precision of autoantibody assays. The scope of this study was to document inter- and intra-run variations of quantitative autoantibody assays based on a real-world large international data set. METHODS: Members of the European Autoimmunity Standardisation Initiative (EASI) group collected the data of intra- and inter-run variability obtained with assays quantifying 15 different autoantibodies in voluntary participating laboratories from their country. We analyzed the impact on the assay performances of the type of immunoassay, the number of measurements used to calculate the coefficient of variation (CVs), the nature and the autoantibody level of the internal quality control (IQC). RESULTS: Data were obtained from 64 laboratories from 15 European countries between February and October 2021. We analyzed 686 and 1,331 values of intra- and inter-run CVs, respectively. Both CVs were significantly dependent on: the method of immunoassay, the level of IQC with higher imprecision observed when the antibody levels were lower than 2-fold the threshold for positivity, and the nature of the IQC with commercial IQCs having lower CVs than patients-derived IQCs. Our analyses also show that the type of autoantibody has low impact on the assay' performances and that 15 measurements are sufficient to establish reliable intra- and inter-run variations. CONCLUSIONS: This study provides for the first time an international repository yielding values of intra- and inter-run variation for quantitative autoantibody assays. These data could be useful for ISO 15189 accreditation requirements and will allow clinical diagnostic laboratories to assure quality of patient results.

The Norwegian experience with nationwide implementation of fetal RHD genotyping and targeted routine antenatal anti-D prophylaxis.

OBJECTIVES: To reduce the risk of RhD alloimmunization during the last trimester of pregnancy, a targeted routine antenatal anti-D prophylaxis (RAADP) programme was implemented in Norway in 2016. Here, we present and discuss our experience with the nationwide implementation of the programme, and report sample uptake and preliminary data of de novo anti-D in pregnancy. BACKGROUND: The targeted RAADP was advised by the academic community and evaluated by the health authorities. A National Working Group has conducted the implementation in the transfusion services and contributed to organise the administration of the antenatal anti-D prophylaxis. Fetal RhD type is determined by non-invasive prenatal testing at gestational week 24, and anti-D prophylaxis is administrated at gestational week 28 only to women with RhD positive fetuses. METHODS: We describe the implementation process of targeted RAADP in Norway. The sample uptake is calculated by comparing the number of fetal RHD screens with the expected number of samples. RESULTS: The sample uptake shows regional variations: 88%-100% after 3 years. Promising decrease in de novo anti-D detected during pregnancy is observed. CONCLUSIONS: Nationwide targeted RAADP is implemented and included in the Norwegian maternity care programme. Compliance to sample uptake should further improve in some regions. A remaining issue to fulfil is the documentation of the accuracy of the fetal RHD-typing at all sites. Post-natal prophylaxis will then be guided by the fetal RHD result. Dedicated registries will ensure data to evaluate the expected reduction in pregnancy-related RhD immunisations, which is the final success criterion of the programme.

Quality and best practice in medical laboratories: specific requests for autoimmunity testing.

Special conditions associated with laboratory autoimmune testing are not well compatible with recent developments in regulatory frameworks such as EN/ISO 15189 accreditation or in vitro diagnostic medical device regulation (IVD-R). In addition, international recommendations, guidelines and disease criteria are poorly defined with respect to requirements on autoantibody testing. Laboratory specialists from Austria, Belgium, Croatia, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, and The Netherlands collected information, reported national experience, and identified quality issues in relation to autoantibody testing that require consensus on interpretation of the regulatory frameworks and guidelines. This process has been organized by the European Autoimmunity Standardisation Initiative (EASI). By identifying the critical items and looking for a consensus, our objective was to define a framework for, in particular, EN/ISO accreditation purposes. Here, we present a review of current publications and guidelines in this field to unify national guidelines and deliver in this way a European handout on quality control and accreditation for laboratories involved in autoantibody testing. We focus on quality items that can be checked during accreditation visits. Despite various local varieties, we encountered an overwhelming dedication to quality assurance in all contributing countries.

Red blood cell destruction in autoimmune hemolytic anemia: role of complement and potential new targets for therapy.

Autoimmune hemolytic anemia (AIHA) is a collective term for several diseases characterized by autoantibody-initiated destruction of red blood cells (RBCs). Exact subclassification is essential. We provide a review of the respective types of AIHA with emphasis on mechanisms of RBC destruction, focusing in particular on complement involvement. Complement activation plays a definitive but limited role in warm-antibody AIHA (w-AIHA), whereas primary cold agglutinin disease (CAD), secondary cold agglutinin syndrome (CAS), and paroxysmal cold hemoglobinuria (PCH) are entirely complement-dependent disorders. The details of complement involvement differ among these subtypes. The theoretical background for therapeutic complement inhibition in selected patients is very strong in CAD, CAS, and PCH but more limited in w-AIHA. The optimal target complement component for inhibition is assumed to be important and highly dependent on the type of AIHA. Complement modulation is currently not an evidence-based therapy modality in any AIHA, but a number of experimental and preclinical studies are in progress and a few clinical observations have been reported. Clinical studies of new complement inhibitors are probably not far ahead.

Erythrocytapheresis compared with whole blood phlebotomy for the treatment of hereditary haemochromatosis.

BACKGROUND: Hereditary haemochromatosis may result in severe organ damage which can be prevented by therapy. We studied the possible advantages and disadvantages of erythrocytapheresis as compared with phlebotomy in patients with hereditary haemochromatosis. MATERIALS AND METHODS: In a prospective, randomised, open-label study, patients with hereditary haemochromatosis were randomised to bi-weekly apheresis or weekly whole blood phlebotomy. Primary end-points were decrease in ferritin levels and transferrin saturation. Secondary endpoints were decrease in haemoglobin levels, discomfort during the therapeutic procedure, costs and technicians' working time. RESULTS: Sixty-two patients were included. Thirty patients were randomised to apheresis and 32 to whole blood phlebotomy. Initially, ferritin levels declined more rapidly in the apheresis group, and the difference became statistically highly significant at 11 weeks; however, time to normalisation of ferritin level was equal in the two groups. We observed no significant differences in decline of transferrin saturation, haemoglobin levels or discomfort. The mean cumulative technician time consumption until the ferritin level reached 50 µg/L was longer in the apheresis group, but the difference was not statistically significant. The cumulative costs for materials until achievement of the desired ferritin levels were three-fold higher in the apheresis group. CONCLUSION: Treatment of hereditary haemochromatosis with erythrocytapheresis instead of whole blood phlebotomy results in a more rapid initial decline in ferritin levels and a reduced number of procedures per patient, but not in earlier achievement of target ferritin level. The frequency of discomfort was equally low with the two methods. The costs and, probably, technician time consumption were higher in the apheresis group.

[Autoimmune hemolytic anemia]. / Autoimmun hemolytisk anemi.

BACKGROUND: Knowledge of autoimmune hemolytic anemia is rapidly increasing, especially on pathogenesis, associated disorders and aspects of transfusion immunology. New treatment options have emerged. MATERIAL AND METHOD: This review is based on selected publications, a non-systematic search in PubMed and the authors' own research. RESULTS: Autoimmune hemolytic anemia is a heterogeneous group of diseases. The warm-antibody type is frequently associated with chronic lymphocytic leukemia or autoimmune systemic disease. Corticosteroids are still the first-line therapy and splenectomy is second-line, while rituximab has become an option in refractory disease. Blood transfusions require specific precautions such as restrictive use, extensive phenotyping of antigens and testing for alloantibodies and biological compatibility. Primary chronic cold agglutinin disease, a subgroup of cold-antibody autoimmune hemolytic anemia, is a clonal lymphoproliferative bone marrow disease. This subgroup is usually refractory to corticosteroids and patients with few clinical symptoms and slight anemia may not require drug therapy. However, in a majority, effective drugs are needed. The best documented therapy is infusions with rituximab, but new options are being tested. Immune hemolytic anemia associated with drugs occurs less frequently now than before. INTERPRETATION: Subgroups and associated or underlying disease should be identified in patients with autoimmune hemolytic anemia. The therapeutic implications of subclassification are important. Patients who have cold agglutinin disease and need therapy should be included in prospective trials.