Aggregates in apheresis-derived platelet concentrates: A 5-year single-centre experience.

BACKGROUND AND OBJECTIVES: The phenomenon of aggregates in apheresis-derived platelet concentrates (APCs) has not yet been fully elucidated. Initially, visible aggregates (IVA) usually dissolve within 24 h after collection, but some persist till the end of the shelf life (persistent aggregates, PA). A study conducted at the Croatian Institute of Transfusion Medicine aimed to identify factors that influence the aggregate occurrence in APCs. MATERIALS AND METHODS: We conducted a cross-sectional study for the 2018-2022 period and collected data on APCs with IVA. We analysed APCs discarded due to PA separately for two apheresis technologies and compared them to the control group. RESULTS: Significantly more donations were discarded in the IVA group compared with the control group and total number of discarded APCs. A total of 205 APCs were discarded due to PA (14.7% of IVA APCs and 1.27% of all APCs collected). Amicus APCs with PA had a significantly lower platelet count and mean platelet volume. They were obtained by procedures with less anticoagulant used. In contrast to Amicus APCs, Haemonetics APCs with PA had a significantly higher platelet count. None of the donor-related factors examined was predictive of PA. CONCLUSION: APCs with IVA are more often discarded, not only due to aggregates, but also for impairment of other quality control parameters. Type of apheresis technology, being one of the most common risk factors for IVA, was not confirmed as the main risk factor for PA. There seem to be some donor-related causal factors.

The role and importance of epidemiology in transfusion medicine.

Transfusion therapy is an indispensable form of treatment, and an important element of the public health system. Due to its origin, blood's clinical use is associated with various risks that may cause adverse reactions and events. Progress in quality and safety of blood components has eliminated numerous risks, especially those of infectious origin. However, some risks cannot be predicted, while others cannot always be prevented. Globalisation and climate change constantly favour the spread of infectious agents. Against this, epidemiology plays a central role in ensuring the safety of transfusion treatment, by continuous surveillance and timely identification of risks, and in the development of routine and additional tests as measures for risk mitigation. As a quantitative discipline based on research methods, epidemiology is a method of reasoning; it relies on the generation and testing of hypotheses; it utilises other scientific resources, particularly in the field of blood donation and blood transfusion, thus having many applications. The main focus falls on transfusion-transmissible infections, and on environmental or occupational diseases, injuries, disabilities and death causes at large. The practice of epidemiology relies on a systematic approach and measurement of disease frequencies. Surveillance is a key element, involving continuously gathering, analysing, and evaluating data regarding diseases, morbidity and mortality, and disseminating the conclusions of the analyses to relevant competent authorities; in this way, action is taken for disease prevention and control. Surveillance systems also provide an important tool for risk assessment, a method to assess and characterise the critical parameters in the functionality of equipment, systems or processes of using scientific data in order to estimate the magnitude of any health effect that derives from decisions of policy makers. Epidemiological surveillance, particularly for the incidence of adverse reactions and adverse events associated with blood transfusion at the national and international levels, has demonstrated the importance of multidisciplinary cooperation between blood and public health services.

Ethics in transfusion medicine: Are the intricate layers of ethics all universal? A global view.

Ethical principles have been considered, and in several respects regulated, along the entire blood procurement chain from donor motivation to transfusion to the patient. Consent of donors and voluntary non-remunerated donation are fields which have been addressed by codes of ethics and legislation. Caring for donor health is an area of further development of ethical standards. In part, blood products have also become a market, where commercial principles may synergize, but also creating issues in equality and maintaining human dignity that challenge societal solutions. At the bedside, the main global challenge remains to procure enough blood products for each patient in medical need. Allocation of rare blood, ethical evaluation of transfusion triggers, attitudes towards refusing blood transfusion and provision of blood products to remote settings are areas which should receive consideration.

Education in transfusion medicine, Part III - The importance of haemovigilance education.

According to the literature, there are significant differences in the availability of education and training in transfusion medicine worldwide, with significant heterogeneity in the existing curricula. Recognising the need for education with the aim of achieving globally standardised competencies in transfusion medicine, a group of experts collaborating in the European and Mediterranean Initiative in Transfusion medicine (EMITm) proposed a process of incremental training and education. Subsequent to two previous papers published by this group on general education in transfusion medicine, this paper specifically refers to the field of education in haemovigilance. This topic is of particular importance when one considers the role of haemovigilance in improving the safety of transfusion practice, and the fact that this role can only be realised through the cooperation of all participants in the transfusion chain. In addition to promoting the importance of education in haemovigilance, this paper provides an overview of the available literature on this topic and proposes an education programme on haemovigilance for medical students and residents.

Thirty years of hemovigilance - Achievements and future perspectives.

Since its emergence in the early 1990s, hemovigilance has gradually evolved from a blood safety concept focused on surveillance of adverse reactions and events in patients, to a well-defined system that monitors the entire transfusion chain and improves its safety. The importance of hemovigilance has been recognized globally in a relatively short time, but the level of its implementation varies significantly between countries. The cooperation of international organizations has significantly contributed to the promotion, implementation, and education in this field. Thanks to initiatives taken, the safety of transfusion practice has been improved in many segments, primarily related to the risks of adverse events in recipients of blood components. In parallel with changing transfusion practice, the hemovigilance process has also matured. In addition to the reduction of existing risks and the early detection of emerging risks, hemovigilance has also embraced the principles of patient blood management. Research in hemovigilance is more increasingly focused on specific categories of patients, specific blood components and methods of their preparation, rare reactions, and transfusion efficacy and efficiency. A proactive approach and use of big data can play an important role in achieving these goals. Additional and sustained efforts should be made to prevent underreporting of events and to improve data comparability through clear definitions and grading systems. This review provides a historical overview of hemovigilance and its achievements, current challenges, and future plans.

IMPACT OF AIR TRANSPORT ON BLOOD SAMPLE QUALITY.

The aim of this study was to establish the impact of air transport on blood samples packaged with and without cooling elements and effect of outdoor temperature on sample quality. Venous samples from 38 blood donors in winter and 36 in summer were tested for hemolysis and complete blood count. One tube per subject was kept in controlled conditions at +4 °C. Two sets of tubes were sent by plane from Zagreb to Brussels, one with and one without cooling elements, and another two sets were sent to London following the same principle. Packages with cooling elements were stored in controlled warehousing conditions at airports (+2 °C to +8 °C), whereas packages without cooling elements were stored in ambient warehouse conditions. Data loggers were used for temperature monitoring. Our research revealed statistically significant differences in several hematologic parameters when comparing the samples stored in controlled laboratory conditions and those transported by plane. These differences were more pronounced in the samples transported during the summer. Transport conditions without cooling elements had additional negative impact on the sample quality. Transport of samples using cooling elements and controlled warehousing conditions at airports are sometimes not sufficient to maintain laboratory storage conditions.

Is Better Standardization of Therapeutic Antibody Quality in Emerging Diseases Epidemics Possible?

During the ongoing COVID-19 epidemic many efforts have gone into the investigation of the SARS-CoV-2-specific antibodies as possible therapeutics. Currently, conclusions cannot be drawn due to the lack of standardization in antibody assessments. Here we describe an approach of establishing antibody characterisation in emergent times which would, if followed, enable comparison of results from different studies. The key component is a reliable and reproducible assay of wild-type SARS-CoV-2 neutralisation based on a banking system of its biological components - a challenge virus, cells and an anti-SARS-CoV-2 antibody in-house standard, calibrated to the First WHO International Standard immediately upon its availability. Consequently, all collected serological data were retrospectively expressed in an internationally comparable way. The neutralising antibodies (NAbs) among convalescents ranged from 4 to 2869 IU mL-1 in a significant positive correlation to the disease severity. Their decline in convalescents was on average 1.4-fold in a one-month period. Heat-inactivation resulted in 2.3-fold decrease of NAb titres in comparison to the native sera, implying significant complement activating properties of SARS-CoV-2 specific antibodies. The monitoring of NAb titres in the sera of immunocompromised COVID-19 patients that lacked their own antibodies evidenced the successful transfusion of antibodies by the COVID-19 convalescent plasma units with NAb titres of 35 IU mL-1 or higher.

Prevalence of ABO and RhD blood group phenotypes in the Croatian population and in patients with severe COVID-19 in Croatia.

BACKGROUND: The aim of this study was to determine the distribution of ABO and RhD blood group phenotypes in the general population in the Republic of Croatia and among hospitalized patients with severe COVID-19. MATERIALS AND METHODS: Data on ABO and RhD blood groups of all blood donors in Croatia (who donated blood during the period 2015-2020) and patients and pregnant women tested at the Croatian Institute of Transfusion Medicine during the 2-year period, 2019-2020, were obtained from the e-Delphyn blood bank information system. A total of 614,673 results were analyzed in this group. The other group consisted of 780 COVID-19 patients hospitalized with severe COVID-19. Data are presented as total number and percentages and a comparison of proportions test was performed. RESULTS: The most frequent ABO phenotype in the general population is A (38%), followed by O (37%), B (18%) and AB (7%). RhD positive individuals accounted for 81% of the general population and RhD negative for the other 19%. Among COVID-19 patients, phenotype A was the most frequent (42%), followed by phenotypes O (32%), B (17%) and AB (9%). Thus blood group A was significantly more common among COVID-19 patients than among the general population, whereas blood group O was significantly less frequent. DISCUSSION: This study provides the first official results of the distribution of ABO and RhD blood group phenotypes in the general population in Croatia. Moreover, this study confirms other researchers' observations about the predominance of the A blood group phenotype among COVID-19 patients.

Post-donation information management.

Post-donation information (PDI) can be defined as any information provided by the donor or other source following a donation, that, had it been known to the blood establishment during the selection process, would have resulted in the donor's deferral. PDI reflects the shortcomings, limitations and complexity of the donor selection process. Knowledge of the causes of PDI events, their types and frequency, is a prerequisite not only for their effective management, but also for the implementation of measures to improve the selection process and the safety of donated blood. Managing PDI requires a considerable investment of time and close collaboration between the various stakeholders involved in this process. Despite its regular occurrence and the fact that PDI points to a possible problem of blood safety, very few studies have been published so far, mostly by US and Canadian authors. This review article aims at collecting and discussing available information on all aspects of PDI management, with particular reference to European experiences.

Blood collection failures from a blood establishment perspective.

OBJECTIVES: The objective of this study was to show experience of the Croatian Institute of Transfusion Medicine in monitoring and analysing collection failures caused by the venepuncture technique or occurred as a result of adverse reactions and complications experienced by donors during donation. BACKGROUND: Collection failures represent one of the leading nonconformities in blood establishments. Apart from being a negative motivating factor for blood donors, they also affect the blood components supply and have a negative financial impact. METHODS: Nonconformity records referring to collection failures were analysed retrospectively over a 6-year period (2013-2018) with regard to their frequency, causes, donor characteristics (age, gender, number of donations), place of occurrence (blood establishment, mobile sessions) and trends during the analysed period. RESULTS: A total of 5166 collection failures out of 618 251 donations (0.84%) were recorded during the analysed period. The leading cause was haematoma at puncture site (1676, i.e., 32.4%). Collection failures which are primarily attributed to the venepuncture technique or vein selection accounted for 91% of all cases, whereas collection failures which occurred as a result of discontinued punctures due to adverse reactions in donors accounted for 9% of all cases. A much higher frequency of all collection failure types was recorded in female donors, whereas younger donors experienced adverse reactions more frequently (median age of 24). CONCLUSION: The analysis and monitoring frequency of collection failures play an important role in planning of staff training activities, work organisation and timely implementation of corrective actions.

Medical student education in transfusion medicine, part II: Moving forward to building up a "Know How" education program in transfusion medicine for under-graduate medical students.

There is a general trend in changing paradigm in teaching medicine; the emerging concept relies on a competence-based approach. Transfusion is either a discipline or a subsidiary of others depending on the countries and systems; this variability can be explained because transfusion is a medical care that is transdisciplinary. As a collective of professionals in both transfusion medicine practice and education, authors aim to propose a revision of the way education in transfusion medicine is delivered in this era of the 'global competency approach'. They advocate in favor of a Know How on 5 key issues: Diagnosing the patient condition in line with the Patient Blood Management principles; Facing acute blood loss; Addressing compatibility and avoiding immunization; Seeking for maximized benefits and dampening complications; and Inlaying competence within global health care issues, also comprising od economy. The methods used would be those developed for medical education at large, such as assessment tools. The global objective is to deliver the necessary competence to manage patients by an intern/resident. At the end of the curriculum, students should be able to self-evaluate the following items: 1) Do I know why my patient is anemic, thrombocytopenic, bleeding….? 2) Do I know the best approach to treat anemia, thrombocytopenia, bleeding (including the "no treatment" option)? 3) Do I know whether a transfusion approach is appropriate for my patients? 4) Do I know how to evaluate and anticipate benefits from blood transfusion and to avoid side-effects in the patient? 5) Do I know how to avoid unnecessary use of the products?

ABO blood groups and psychiatric disorders: a Croatian study.

BACKGROUND: The prevalence of ABO alleles is different in different populations, and many studies have shown a correlation between the occurrences of some diseases and different genotypes of ABO blood groups. The aim of this study was to determine whether there is a significant association between psychiatric syndromes and ABO blood groups. MATERIALS AND METHODS: This case-control study involved 156 psychiatric patients and 303 healthy, unrelated, voluntary blood donors. Genomic DNA was isolated from blood on a QIAcube device using a QIAamp DNA Blood mini QIAcube kit. ABO genotyping on five basic ABO alleles was performed using allele-specific polymerase chain reaction analysis. RESULTS: Compared with healthy subjects, a significantly higher proportion of psychiatric patients had AB blood group (χ2=9.359, df=3, p=0.025) and, accordingly, a significantly higher incidence of A1B genotype (χ2=8.226, df=3, p=0.042). The odds ratio showed that psychiatric disorders occur almost three times more frequently in carriers of AB group compared to other blood groups. However, no statistically significant difference was found in the distribution of ABO blood groups among patients with different psychiatric diagnoses. Likewise, no correlations were found between ABO blood groups and other characteristics of the psychiatric patients (sex, psychiatric heredity, somatic comorbidity, suicidality). CONCLUSIONS: The results of this study support the hypothesis of an association between psychiatric disorders and ABO blood groups. The probability is that psychiatric disorders will occur almost three times more frequently in carriers of AB group compared to other ABO blood groups in the Croatian population.

Medical student education in transfusion medicine: Proposal from the "European and Mediterranean initiative in transfusion medicine".

A large body of observations indicate that there is an inconsistent knowledge of Transfusion Medicine among health care professionals as well as inconsistent knowledge in all aspects of the transfusion process, from blood donation to transfusion on the ward. It is obvious to consider that appropriate education in Transfusion Medicine should be achieved in the education of specialists who will prescribe transfusion on a regular basis (hematologists, critical care specialists, anaethesiologists and others.) However,we also believe that education in Transfusion Medicine should also be delivered to almost all other medical specialists who may prescribe blood components. The variability in education of undergraduates in medical schools is universal most likely due to an absence of a predefined common platform. This paper, therefore, focuses on education at the undergraduate level and advocates coverage of the essential physiology and pathophysiology of blood as applied to blood transfusion as well as the medical and societal aspects of issues related to blood donation. It proposes incremental levels of training in Transfusion Medicine, with what is being therefore referred to as 'A', 'B', 'C' etc. curricula in ascending order of complexity; for example, 'A' and 'B' levels would involve medical, midwifery and nursing students, covering a broad base of the subject: they will be detailed in the present essay; ongoing further curricula will focus on physicians and other professionals working within the area or with responsibility for different aspects of the transfusion chain. It is intended that these courses include aspects of donor care, patient care and the appropriate use, safety and effectiveness of blood products. Next, it is advocated that curricula are addressed not only for high-income countries but also for middle- and low-income ones.

Three-Year Experience in NAT Screening of Blood Donors for Transfusion Transmitted Viruses in Croatia.

BACKGROUND: Croatia implemented individual donation (ID)-NAT testing of blood donors in 2013 for three viruses HBV, HCV, and HIV-1 as a mandatory test for all blood donors. This study assessed the impact of NAT screening 3 years after its implementation. METHODS: A total of 545,463 donations were collected and screened for HBV, HCV, and HIV-1 using the Procleix Ultrio Plus Assay. All initially reactive (IR) NAT samples were retested in triplicate and, if repeatedly reactive (RR), NAT discriminatory assay (dNAT) was performed. ID-NAT positive donations were confirmed by RT-PCR on the COBAS AmpliPrep/TaqMan platform. RESULTS: Out of 545,463 samples tested, 108 (0.02%) were RR in NAT. There were 82 (75,9%) HBV reactive, 16 (14.8%) HCV reactive, and 10 (9.3%) HIV-1 reactive samples. 51 (47.2%) samples were ID-NAT positive only. Out of these 51 NAT yield cases, 1 window period HIV-1 and 50 occult HBV infections (OBI) were determined. There were only two potential HBV DNA transmissions from OBI donors. CONCLUSION: The implementation of NAT screening for three viruses has improved blood safety in Croatia. During the 3-year period, 1 window period HIV-1 and a number of occult HBV donations were identified.

Blood donor selection in European Union directives: room for improvement.

BACKGROUND: Transfusion-transmissible infections have made both blood bankers and health authorities overly cautious. The general public expects and hence reinforces this policy. To obtain a high level of blood product safety, blood and plasma donors have to meet increasingly stringent eligibility criteria; however, it is not known whether this policy translates into improved outcomes for patients. There is a risk that the management of donors does not match the ambition of greater safety for patients. European directives related to the collection process and donor selection will probably be reconsidered in the next few years. MATERIAL AND METHODS: The development of European directives on donor selection and their basis in the literature were reviewed with an emphasis on the background and considerations for eligibility criteria to be included in the directives. RESULTS: The precautionary principle appears to be the predominant reason behind the set of eligibility criteria. However, the formal eligibility criteria, put into force in 2004, do not balance with the developments of the past decade in laboratory tests and measures that have substantially reduced actual infection risks. In no cases were the effects of eligibility criteria on the donor pool and donor well-being quantified. Regional differences in the epidemiology of transfusion-transmissible infections were not taken into consideration either. DISCUSSION: First, the Authors promote the collection of epidemiological data on the incidence and prevalence of conditions in the general population and in blood and plasma donors which could pose a risk for transfused patients, in order to use these data as a basis for decision-making in donor-selection policies. Second, the Authors suggest including allowance for differential deferral criteria throughout Europe, based on factual risk levels. There should be an accepted balance between donor and patient welfare, and also between risk to transfusion safety and risk of compromising the blood supply.