A donor safety evidence literature review of the short- and long-term effects of plasmapheresis.

Many blood establishments are expanding plasmapheresis collection capacity to achieve increasing plasma for fractionation volume targets, driven by immunoglobulin product demand. Some adverse events occur in both apheresis and whole blood collection, such as venepuncture-related trauma and vasovagal reactions. Others are specifically related to the apheresis procedure, such as citrate reactions, haemolysis, infiltration and air embolism. Whilst plasmapheresis procedures are generally well tolerated, theoretical longer term donor health considerations, such as the effects on donor plasma protein levels, bone mineral density, iron deficiency and malignancy also require consideration. An evidence-based framework that supports a safe and sustainable increase in the collection of plasma is essential. Our review demonstrates a lack of high-quality evidence on risks and outcomes specifically in plasmapheresis. Whilst conservative procedural controls and donor harm minimization policies will mitigate risk, high-quality evidence is needed to facilitate practice change that is safe and sustainable and maximizes the potential of individual donor differences.

Donor and recipient safety in human milk banking.

AIM: Australian Red Cross Lifeblood supplies pasteurised donor human milk (PDHM) to more than 30 partner hospitals across Australia. Preterm infants who receive PDHM are a highly vulnerable population but formal biovigilance programs are rare in human milk banking. Lifeblood Milk performs ongoing surveillance for both donor and recipient adverse events. This study aimed to formally review adverse events reported to Lifeblood Milk since 2018. METHODS: Milk donor infectious diseases testing outcomes and donor adverse events (DAEs) are prospectively recorded at Lifeblood. Infant recipient adverse events are contractually reported back to Lifeblood Milk by hospitals and assessed according to severity and likelihood of relationship to PDHM administration. Donor and recipient adverse events over a 3.5-year period (July 2018 to December 2021) were reviewed. RESULTS: There were three DAEs (3/976 = 0.31%) related to phlebotomy; these included two vasovagal reactions and one phlebotomy site haematoma. Eight (8/976 = 0.81%) additional donors had biological false reactive (BFR) infectious diseases serology results. There were 10 reported suspected adverse events in recipients. Six were infection-related; other events included milk curd obstruction, high urinary iodine levels, sudden cardiac death and nasogastric tube obstruction. All reported suspected adverse events in recipients were classified as unlikely to be related, or definitely not related, to PDHM administration. CONCLUSIONS: Milk donor adverse events were rare but biological false reactive serology results were not uncommon. There were no recipient adverse events considered causally related to pasteurised donor human milk, which is generally a low-risk biological product. Ongoing biovigilance remains essential.

A Systematic Review of Interventions Used to Increase Blood Donor Compliance with Deferral Criteria.

BACKGROUND AND OBJECTIVES: Pre-donation screening of potential blood donors is critical for ensuring the safety of the donor blood supply, and donor deferral as a result of risk factors is practised worldwide. This systematic review was conducted in the context of an expert review convened by the Australian Red Cross Lifeblood in 2013 to consider Lifeblood's injecting drug use (IDU)-related policies and aimed to identify studies assessing interventions to improve compliance with deferral criteria in blood donation settings. MATERIALS AND METHODS: MEDLINE/PubMed, OVID Medline, OVID Embase, LILACS, and the Cochrane Library (CENTRAL and DARE) databases were searched for studies conducted within blood donation settings that examined interventions to increase blood donor compliance with deferral criteria. Observational and experimental studies from all geographical areas were considered. RESULTS: Ten studies were identified that tested at least one intervention to improve blood donor compliance with deferral criteria, including computerized interviews or questionnaires, direct and indirect oral questioning, educational materials, and a combination of a tickbox questionnaire and a personal donor interview. High-quality evidence from a single study was provided for the effectiveness of a computerized interview in improving detection of HIV risk behaviour. Low-quality evidence for the effectiveness of computerized interviews was provided by 3 additional studies. Two studies reported a moderate effect of direct questioning in increasing donor deferral, but the quality of the evidence was low. CONCLUSION: This review identified several interventions to improve donor compliance that have been tested in blood donation settings and provided evidence for the effectiveness of computerized interviews in improving detection of risk factors.

Frequency of rare, serious donor reactions: International perspective.

BACKGROUND: Severe blood donor adverse events are rare, but due to their rarity studying them can be difficult. To get an accurate estimate of their frequency and rate in the donor population it may be necessary to combine donation data across countries. STUDY DESIGN AND METHODS: International blood collection organizations (BCOs) provided data on rare/severe donor reactions as well as denominator information for their donor populations from 2015 to 2017. Donor reactions were classified using standardized definitions. RESULTS: BCOs from six countries provided reaction data for more than 22 million donations. A total of 480 rare reactions were reported of which 76.7% were imputed as definite and 11% probable. Rates of rare reactions were higher in females and first-time donors. Systemic rare reactions were the most common reaction type, accounting for over three quarters of reactions reported. Of systemic reactions, vasovagal reactions with loss of consciousness and injury or off-site (n = 350) made up the majority and occurred 1.53 per 100,000 donations. For the 22.3% that were localized reactions, the majority of these were cellulitis (n = 71, 0.31 per 100,000 donations) followed by deep venous thrombosis (n = 21, 0.09 per 100,000 donations). CONCLUSION: Pulling together data from multiple BCOs across countries allows for a better understanding of rare reactions, such as vasovagal reaction with injury or cellulitis, and for generating a reliable incidence rate for air embolism or compartment syndrome. However, gaps remain due to missing elements such as unknown donor status or location of reaction.

SARS Coronavirus-2 Microneutralisation and Commercial Serological Assays Correlated Closely for Some but Not All Enzyme Immunoassays.

Serological testing for SARS-CoV-2-specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. Sera from recovered patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n = 200), and negative control sera collected prior to the COVID-19 pandemic (n = 100), were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. Neutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. These results suggest the marker used (total Ab vs. IgG vs. IgA) and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrates their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation.

What are Optimal Bacteriological Screening Test Cut-Offs for Pasteurized Donor Human Milk Intended for Feeding Preterm Infants?

BACKGROUND: Definitive criteria for microbial screening of pasteurized donor human milk are not well established and international recommendations vary. AIMS: (1) To review pasteurized donor human milk batch discard due to failed microbial screening criteria at our milk bank (following United Kingdom National Institute of Clinical Excellence guidelines), and (2) to compare our known milk discard proportion with estimated milk discard proportions that would be required by other international milk bank guidelines. METHODS: We reviewed our microbial screening results (N = 783) over 18-months (July 2018-December 2019) and compared our known milk discard proportion with estimated milk discard proportions using other international milk bank guidelines. RESULTS: Of samples, n = 50 (6.4%) failed pre-pasteurization screening, most commonly due to the presence of >104 CFU/mL Enterobacterales in the pre-pasteurization sample (n = 30; 3.8%). Two (0.3%) samples failed post-pasteurization screening, with Bacillus cereus identified in both cases, resulting in total discard proportion of 6.7% (n = 52) of batches. Applying European Milk Bank Association recommended bacterial screening criteria, approximately 23.3% (n = 183) of milk batches would have been discarded. CONCLUSIONS: Further research is required to justify the stringent European Milk Bank Association recommendations for pre-pasteurization discard criteria, although we believe that a post-pasteurization acceptance criterion of <1 CFU/mL is appropriate and aligns with international guidance. Further work is needed to understand pasteurized donor human milk microbiological safety risks, to better integrate screening criteria within current food standards regulation, and to consider risk-based assessment including the impact on availability and affordability.

Development and evaluation of formal guidelines for donor selection for human milk banks.

AIM: Donor selection for milk banks is essential to ensure the safety and nutritional quality of the donor milk, and to ensure that the prospective donor and her breastfeeding infant do not come to harm through donating. Australian Red Cross Lifeblood Milk went through a robust process to develop a set of criteria for the selection and screening of potential breast milk donors, which included development of a Donor Questionnaire (DQ), supported by a formal set of Guidelines for the Selection of Milk Donors. Key screening questions from the DQ were made available to prospective donors to self-screen prior to the formal assessment process. The aim of this study was to review the outcomes of milk donor screening at Lifeblood Milk. METHODS: We reviewed the outcomes of our donor screening process over the first 12-months (July 2018-June 2019) of operations. RESULTS: A total of 50 out of 327 donors who responded to the self-screening questions were not able to proceed further; 201 donors were formally screened using the DQ and Guidelines for the Selection of Milk Donors, with 9 of 201 deferred based on their responses. An additional two donors were deferred (failed phlebotomy (n = 1) and reactive infectious disease serology (n = 1)), with 190 of 201 (95%) of prospective donors accepted after screening. CONCLUSIONS: Our experience highlighted international differences in practice between milk banks and lack of strong research to inform milk donor selection. Making a set of key screening questions available to donors for self-screening resulted in a high acceptance rate (95%) for donors who began the formal screening process. Further work is needed to better understand the impact of deferral on prospective milk donors.

Trends in platelet distributions from 2008 to 2017: a survey of twelve national and regional blood collectors.

BACKGROUND: This multi-national study evaluated changes in platelet (PLT) unit distributions at 12 national or regional blood collectors over a 10-year period. METHODS: Data on the total number of PLT distributions, the collection method, that is apheresis vs whole blood-derived (WBD), the PLT unit characteristics and post-collection modifications were obtained from 12 national or regional blood collectors from 2008 through 2017. Individual WBD PLT units were converted to apheresis equivalent units (i.e. a dose of PLTs) by dividing by 4, the typical pool size; WBD units that were pooled before distribution were counted as a single dose. RESULTS: Overall at these 12 blood collectors, the total number of PLTs distributed in 2008 was 1 373 200, which rose by 10·2% to 1 513 803 in 2017. The Japanese Red Cross, which distributes only apheresis PLTs, had a 13·4% increase in the number of distributions between the years 2008 and 2017, while the other 11 blood collectors combined demonstrated a 6·8% increase in distributions between these two years. Between the years 2008 and 2017, the changes in the proportion of apheresis, platelet-rich plasma and buffy coat PLT distributions were -29·9%, -70·7% and 80·0%, respectively. CONCLUSION: The number of PLT distributions increased during the 10-year study period despite prophylactic PLT transfusion thresholds having remained fairly consistent over the last decade. Perhaps this increase is in part driven by increased administration of platelets to patients with massive haemorrhage or an increase in stem cell transplantation. The use of buffy coat PLTs is increasing at these collectors.

Blood donation amongst people who inject drugs in Australia: research supporting policy change.

BACKGROUND AND OBJECTIVES: Until recently, people in Australia with a history of injection drug use (IDU) were deferred indefinitely from donating blood. Knowledge gaps regarding policy non-compliance and the prevalence of blood donation practices amongst people who inject drugs (PWID) precluded changes to this policy. We sought to address these gaps and to estimate the additional risk to Australia's blood supply associated with changing the indefinite deferral policy to 1 or 5 years since last injecting episode. MATERIALS AND METHODS: Data on blood donation amongst PWID were collected from 1853 interviews across two Australian studies of PWID conducted during 2015/16. Mathematical modelling was used to estimate the additional risk of hepatitis C (HCV)-infected window period collections as a result of changing the deferral policy. RESULTS: A very few (2-4%) study participants reported ever donating blood after ≥1 IDU episode. Changing the deferral policy from indefinite to 1 or 5 years was estimated to result in an additional 0·00000070 (95%CI: 0·00000033-0·00000165) or 0·00000020 (95%CI: 0·00000008-0·00000041) HCV-positive window period collections per year, respectively. CONCLUSION: Changing Australia's indefinite deferral period to 1 or 5 years since last injecting episode poses a negligible increase in the risk of HCV-infected window period collections from blood donors with a history of IDU. Our results informed a successful submission to the Australian regulator to change the deferral period from indefinite to 5 years since last injecting episode, a policy which came into effect in September 2018.

Quality of Evidence-Based Guidelines for Transfusion of Red Blood Cells and Plasma: A Systematic Review.

Many transfusion guidelines are available, but little appraisal of their quality has been undertaken. The quality of guidelines may potentially influence adoption. Our aim was to determine the quality of evidence-based transfusion guidelines (EBG) for red cells and plasma, using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and assess duplication and consistency of recommendations. MEDLINE and EMBASE were systematically searched for EBG from 2005 to June 3, 2016. Citations were reviewed for inclusion in duplicate. A guideline was included if it had a specified clinical question, described a systematic search strategy, included critical appraisal of the literature and a description of how recommendations were developed. Four to six physicians used AGREE II to appraise each guideline. Median and scaled scores were calculated, with each item scored on a scale of one to seven, seven representing the highest score. Of 6174 citations, 30 guidelines met inclusion criteria. Twenty six guidelines had recommendations for red cells and 18 included recommendations for plasma use. The median score, the scaled score and the interquartile range of the scaled score were: scope and purpose: median score 5, scaled score 60%, IQR (49-74%); stakeholder involvement 4, 43%, (33-49%); rigor of development 4, 41%, (19-59%); clarity of presentation 5, 69%, (52-81%); applicability 1, 16%, (9-23%); editorial independence 3, 43%, (20-58%). Sixteen guidelines were evaluated to have a scaled domain score of 50% or less. Variations in recommendations were found for the use of hemoglobin triggers for red cell transfusion in patients with acute coronary syndromes and for plasma use for patients with bleeding. Our findings document, limited rigor in guideline development and duplication and inconsistencies in recommendations for the same topic. The process of developing guidelines for red cells and plasma transfusion can be enhanced to improve implementation.

Re-examining blood donor deferral criteria relating to injecting drug use.

BACKGROUND AND AIMS: Potential Australian blood donors are deferred indefinitely if they report a history of injecting drug use (IDU), or for 12 months if they report having engaged in sexual activity with someone who might have ever injected. Given incremental improvements in blood safety, this study sought to examine whether Australia's IDU-related eligibility criteria reflected current scientific evidence, were consistent with international best practice and, if current IDU-related policies were to be changed, how this should happen. METHODS: An expert committee was formed to review relevant literature with a focus on issues including: the epidemiology of IDU in Australia and key transfusion-transmissible infections (TTIs) among Australian people who inject drugs (PWID); and, 'non-compliance' among PWID regarding IDU-related blood donation guidelines. International policies relating to blood donation and IDU were also reviewed. Modelling with available data estimated the risk of TTIs remaining undetected if the Blood Service's IDU-related guidelines were changed. RESULTS: Very few (<1%) Australians engage in IDU, and IDU risk practices are reported by only a minority of PWID. However, the prevalence of HCV remains high among PWID, and IDU remains a key transmission route for various TTIs. Insufficient data were available to inform appropriate estimates of cessation and relapse among Australian PWID. Modelling findings indicated that the risk of not detecting HIV becomes greater than the reference group at a threshold of non-admission of being an active PWID of around 1.8% (0.5-5.1%). Excluding Japan, all Organisation for the Economic Co-operation and Development member countries permanently exclude individuals with a history of IDU from donating. CONCLUSION: Numerous research gaps meant that the study's expert Review Committee was unable to recommend altering Australia's current IDU-related blood donation guidelines. However, having identified critical knowledge gaps and future areas of research, the review made important steps toward changing the criteria.

Postdonation iron replacement for maintaining iron stores in female whole blood donors in routine donor practice: results of two feasibility studies in Australia.

BACKGROUND: Iron deficiency represents a risk to donor health and the blood supply. Efficacy trials indicate that postdonation iron replacement improves iron stores but they do not account for complexities of implementation in the routine collection context. We therefore conducted two prospective feasibility studies in Australian donor centers. STUDY DESIGN AND METHODS: In both studies we recruited female donors between 18 and 45 years who had made at least one donation in the previous 12 months. In READ (replacement advice), female donors were given a recommendation to self-procure postdonation iron. In DIRECT (donor iron replacement), donors were provided with a course of iron supplements. Donors could return to donate at their discretion and were surveyed after the recruitment visit and again toward the end of the 13-month follow-up. Donor uptake, adverse effects, effectiveness in maintaining iron stores, and workflow impact were assessed. RESULTS: We recruited 1404 (70.9% of invited) donors to READ and 768 (53.2% of invited) to DIRECT. READ and DIRECT extended predonation interviews by 1 and 5 minutes, respectively. Among participants, 44 and 88% took iron in READ and DIRECT, respectively. Adverse effects were common but usually mild. READ failed to maintain iron stores in the population, but was effective in donors who consumed more than 75% of the recommended dose. DIRECT was effective in preventing declines in ferritin concentration. CONCLUSION: Trade-offs between cost, complexity, uptake, and effectiveness must be considered in the implementation of postdonation iron supplementation.

A national review of the clinical use of group O D- red blood cell units.

BACKGROUND: There has been an international decline in the demand for red blood cell (RBC) units. In Australia, there has been a 21% reduction in demand between 2012 and 2015. In contrast, the demand for the "universal" group O D- RBC units is in fact proportionally increasing. STUDY DESIGN AND METHODS: The clinical use of the entire O D- RBC distribution for a 5-week period throughout Australia was reviewed. Fate data on each unit issued (n = 9733) were collected that included the indication and urgency of transfusion, reason for discard, component age, and patient demographics. RESULTS: A total of 74% of audit forms were returned (n = 7143). The national discard rate of issued units was 7.9%. A total of 6387 units were transfused into an estimated total of 3008 patients (55% males) with median patient age of 67 years and median RBC age of 21 days. Forty-seven percent were transfused to group O D- patients. A total of 17.4% were chosen for specific phenotype requirements, 24.5% of units were transfused close to expiry, and 24.5% were transfused into patients of other ABO groups. CONCLUSION: The data appear broadly representative of the current transfusion and inventory management practices surrounding the use of group O D- RBC units. Strategies to reduce O D RBC demand include reevaluation of inventory holdings particularly at smaller centers, increasing the panel of phenotyped RBC units across all ABO groups, more regular rotation of units between hospitals to minimize time expiry, and continuing education for promoting transfusion of ABO-identical RBC units.

A refined method for estimating the size of the potential blood donor pool in Australia.

BACKGROUND: To be eligible to donate blood, potential donors must meet certain eligibility criteria to ensure safety to the donor and to the blood supply. In Australia, there is no reliable estimate of the size of the donor-eligible population. This study uses a refinement to a published method to determine the population prevalence of donor-exclusion factors and subsequently estimates the size of the potential donor pool in Australia. STUDY DESIGN AND METHODS: A total of 70 donor-exclusion factors (in addition to age) were identified. The donor-eligible population was estimated by subtracting the prevalence of the exclusion factors from the total population. Prevalence of the donor-exclusion factors was adjusted for age, deferral period, and overlap of multiple conditions. Overlap was adjusted by extending a published random-probability model according to known association of epidemiologic data on overlapping conditions. RESULTS: The most prevalent (deferral period-adjusted) donor-exclusion factor among the 16- to 80-year-old Australian population was variant Creutzfeldt-Jakob disease-related travel risk (6.8%) followed by upper respiratory tract infections (6.4%). After exclusion of all factors, and accounting for overlapping factors, 62% of 16- to 80-year-olds or 47.3% of the total population were donor eligible in Australia. CONCLUSION: We developed a refined method for estimating the size of the donor-eligible population. Applying this method to Australia, we estimate that approximately 10.7 million people (62% of the 16- to 80-year-olds) were eligible to donate blood in Australia in 2012.

Understanding noncompliance with selective donor deferral criteria for high-risk behaviors in Australian blood donors.

BACKGROUND: Using a predonation screening questionnaire, potential blood donors are screened for medical or behavioral factors associated with an increased risk for transfusion-transmissible infection. After disclosure of these risks, potential donors are deferred from donating. Understanding the degree of failure to disclose full and truthful information (termed noncompliance) is important to determine and minimize residual risk. This study estimates the prevalence of, and likely reasons for, noncompliance among Australian donors with the deferrals for injecting drug use, sex with an injecting drug user, male-to-male sex, sex worker activity or contact, and sex with a partner from a high-HIV-prevalence country. STUDY DESIGN AND METHODS: An anonymous, online survey of a nationally representative sample of Australian blood donors was conducted. Prevalence of noncompliance with deferrable risk categories was estimated. Factors associated with noncompliance were determined using unadjusted and adjusted odds ratios. RESULTS: Of 98,044 invited donors, 30,790 donors completed the survey. The estimated prevalence of overall noncompliance (i.e., to at least one screening question) was 1.65% (95% confidence interval CI, 1.51%-1.8%). Noncompliance with individual deferrals ranged from 0.05% (sex work) to 0.54% (sex with an injecting drug user). The prevalences of the disclosed exclusionary risk behaviors were three to 14 times lower than their estimated prevalence in the general population. CONCLUSION: The prevalence of noncompliance is relatively low but our estimate is likely to be a lower bound. The selected high-risk behaviors were substantially less common in blood donors compared to the general population suggesting that self-deferral is effective. Nevertheless, a focus on further minimization should improve the blood safety.