How do I think about blood donor eligibility criteria for medical conditions?

Every blood center must determine blood donor eligibility criteria for donors with medical conditions, often based on very limited published data and variable practice. This manuscript briefly outlines possible impacts of donor medical conditions on donor and recipient safety and product quality, and describes the multidisciplinary approach used in Canada to think about donor criteria issues. Many years of experience are distilled into practical considerations in determining criteria, possible sources of information, and factors for successful change implementation, to hopefully assist medical and technical staff engaged in decision-making around donor eligibility.

Preparedness and activities of the anti-SARS-CoV-2 convalescent plasma bank in the Veneto region (Italy): An organizational model for future emergencies.

BACKGROUND: Convalescent plasma (CP) has been used in the past in various pandemics, in particular in H1N1, SARS and MERS infections. In Spring 2020, when ongoing the SARS-CoV-2 pandemics, the Veneto Region (V-R) has proposed setting-up an anti-SARS-CoV-2 CP (CCP) Bank, with the aim of preparing a supply of CCP immediately available in case of subsequest epidemic waves. MATERIALS AND METHODS: Key-points to be developed for a quick set-up of the V-R CCP Bank have been recruitment of donors recovered from COVID-19 infection, laboratory analysis for the biological qualification of the CCP units, including titre of neutralizing antibodies and reduction of pathogens, according to National Blood Centre (CNS) Directives, adaptation of the V-R Information Technology systems and cost analysis. Some activities, including diagnostic and viral inactivation processes, have been centralized in 2 or 3 sites. Laboratory analysis upon preliminary admission of the donor included all tests required by the Italian laws and the CNS directives. RESULTS: From April to August 2020, 3,298 people have contacted the V-R Blood Transfusion Services: of these, 1,632 have been evaluated and examined as first time donors and those found to be suitable have carried out 955 donations, from which 2,626 therapeutic fractions have been obtained, at a cost around 215,00 Euro. Since October 2020, the number of COVID-19 inpatients has had a surge with a heavy hospital overload. Moreover, the high request of CCP therapy by clinicians has been just as unexpected, showing a wide therapeutic use. CONCLUSIONS: The organizational model here presented, which has allowed the rapid collection of a large amount of CCP, could be useful when facing new pandemic outbreaks, especially in low and middle income countries, with generally acceptable costs.

Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society.

Donation after circulatory death (DCD) donors are an increasingly more common source of livers for transplantation in many parts of the world. Events that occur during DCD liver recovery have a significant impact on the success of subsequent transplantation. This working group of the International Liver Transplantation Society evaluated current evidence as well as combined experience and created this guidance on DCD liver procurement. Best practices for the recovery and transplantation of livers arising through DCD after euthanasia and organ procurement with super-rapid cold preservation and recovery as well as postmortem normothermic regional perfusion are described, as are the use of adjuncts during DCD liver procurement.

HIV transmission network analysis allows identifying unreported risk factors in HIV-positive blood donors in France.

OBJECTIVES: As sex between men is a major route of human immunodeficiency virus (HIV) infection in most western countries, restrictive deferral rules for blood donation have largely been implemented regarding men having sex with men (MSM). Here, we sought here to assign unreported HIV risk factors in blood donors (BDs) and reevaluated the MSM-associated fraction of HIV transfusion residual risk (%RRMSM ). METHODS: We applied a genetic distance-based approach to infer an HIV transmission network for 384 HIV sequences from French BDs and 1337 HIV sequences from individuals with known risk factors (ANRS PRIMO primary HIV infection cohort). We validated the possibility of assigning a risk factor according to clustering using assortative mixing. Finally, we recalculated the %RRMSM . RESULTS: A total of 81 of 284 (28.5%) male and 5 of 100 (5%) female BDs belonged to a cluster; 72 (88.9%) of the 81 male BDs belonged to MSM clusters. After cluster correction, 8 of 67 (11.9%), 4 of 21 (19.0%), and 19 of 88 (21.6%) HIV-positive (HIV+) male BDs with heterosexual, other, or unknown risk factors could be reclassified as MSM, accounting for 10.9% of the total HIV+ male BDs. Overall, 139 of 284 HIV+ male donors (48.9%) could be considered MSM between 2000 and 2016 in France. Between 2005 and 2016, the %RRMSM increase varied from 0 to 19%, without differing significantly from the %RRMSM before reclassification. CONCLUSION: Network inference can be used to complement declaration data on risk factors for HIV infection in BDs. This approach, complementary to behavioral studies, is a valuable tool to evaluate the effect of changes in deferral criteria on BD compliance.

Whole blood donor behavior and availability after deferral: Consequences of a new ferritin monitoring policy.

BACKGROUND: To prevent (negative consequences of) temporary deferral due to low hemoglobin, the Dutch national blood service Sanquin introduced a ferritin monitoring policy in 2017. Ferritin is measured after the donation (as opposed to before donation for hemoglobin), and low ferritin levels lead to deferral of 6 (ferritin 15-30 ng/mL) or 12 months (ferritin <15 ng/mL). We explored the consequences of this policy on donor behavior and availability. STUDY DESIGN AND METHODS: We included all Dutch whole blood donors who made a donation (attempt) between 13 November and 31 December 2017. At that point, the ferritin monitoring policy was randomly implemented in 8 of 29 regional clusters of collection centers. We extracted information from Sanquin's donor database about donors' deferrals, subsequent donation attempts, and donation cessation (up to 31 December 2019). Donors deferred for low ferritin were compared to those deferred for low hemoglobin or other reasons, as well as to donors who were not deferred. RESULTS: A total of 55 644 donors were included (11% deferred). For donor behavior, we found that donors deferred for low ferritin less often unsubscribed and switched to other donation types, yet also made fewer donations in the follow-up period. For availability, we found they were less often deferred, yet they were unavailable to donate for a longer period. CONCLUSION: Results suggest that the implementation of a ferritin monitoring policy may lead to a decrease in donor availability and reduced donations. However, the policy is successful in retaining more donors and reducing low hemoglobin deferrals.

Uncontrolled Donation After Circulatory Death: A Unique Opportunity.

Uncontrolled donation after circulatory death (uDCD) refers to donation from persons who die following an unexpected and unsuccessfully resuscitated cardiac arrest. Despite the large potential for uDCD, programs of this kind only exist in a reduced number of countries with a limited activity. Barriers to uDCD are of a logistical and ethical-legal nature, as well as arising from the lack of confidence in the results of transplants from uDCD donors. The procedure needs to be designed to reduce and limit the impact of the prolonged warm ischemia inherent to the uDCD process, and to deal with the ethical issues that this practice poses: termination of advanced cardiopulmonary resuscitation, extension of advanced cardiopulmonary resuscitation beyond futility for organ preservation, moment to approach families to discuss donation opportunities, criteria for the determination of death, or the use of normothermic regional perfusion for the in situ preservation of organs. Although the incidence of primary nonfunction and delayed graft function is higher with organs obtained from uDCD donors, overall patient and graft survival is acceptable in kidney, liver, and lung transplantation, with a proper selection and management of both donors and recipients. Normothermic regional perfusion has shown to be critical to achieve optimal outcomes in uDCD kidney and liver transplantation. However, the role of ex situ preservation with machine perfusion is still to be elucidated. uDCD is a unique opportunity to improve patient access to transplantation therapies and to offer more patients the chance to donate organs after death, if this is consistent with their wishes and values.

[Our new donation law: more autonomy?] / Onze nieuwe donorwet ­ meer autonomie?

On 1 July 2020, the registration of organ and tissue donors in the Netherlands changed from an opt-in to an opt-out system. This means that everyone in the Netherlands will be registered as an organ and tissue donor unless they have registered a different choice in the donor register. The hope is that this new method for donor registration will lead to more donors. Only a small majority of members of the Senate and the House of Representatives in the Netherlands voted for the legislative amendment that enabled this new system to come into effect. In the Senate the amendment was defended on the grounds that it would do more justice to the autonomy of the deceased; the new law will, however, have to be defended from the principles of justice and solidarity by a government that feels responsibility towards those needing a donor organ.

Attitudes and willingness to donate blood among gay and bisexual men in Australia.

BACKGROUND: Men who have sex with men in Australia are currently ineligible to donate blood (are "deferred") for 12 months since last oral or anal sexual contact with another man. In Australia and overseas, there has been limited research on attitudes and perceptions related to blood donation in this population. STUDY DESIGN AND METHODS: Questions on blood donation histories and attitudes toward the deferral policy were included in the questionnaire of an online prospective cohort of gay and bisexual men (GBM) living in Australia. RESULTS: In 2018, 1595 GBM responded to the survey. In this sample, 28.7% reported previously donating blood. Among the remaining men who had never donated blood, 64.5% expressed an interest in doing so. Nearly all men indicated they were not willing to abstain from sex with another man for 12 months in order to donate, and the vast majority believed the rule was unfair, too strict, and homophobic. Three-quarters (77.7%) said that if the policy changed, they would likely donate blood. Age and openness about one's sexuality were independently associated with one's willingness to donate blood in the absence of the deferral. CONCLUSION: There was a high level of willingness and desire to donate blood among GBM. However, rather than abstaining from sex in order to donate, many men comply with the deferral policy and do not donate. A less conservative deferral policy may increase donations from GBM.

Living-unrelated kidney donor transplantation: Legalization in exceptional circumstances?

The prevalence of end-stage renal disease (ESRD) morbidity and mortality is mounting. Kidney transplantation offers a good means of survival and improves longevity of patients with ESRD. However, not everyone is fortunate to benefit from this lifesaving renal replacement therapy due to the lack of available kidneys, one of the many reasons. It eventually expands the number of patients on waiting list of kidney transplantation. At present, deceased and living-related kidney donor transplantation models are widely used, but with limited success to keep up with the pace of burgeoning ESRD. A debate over the legalization of unrelated living kidney donor transplantation has erupted lately. This short review articles focuses on issues surrounding kidney transplantation in Pakistan and draws an informed conclusion regarding pragmatic legalization of unrelated living kidney donor transplantation in exceptional circumstances. Finally, this article also offers a food for thought for countries facing analogous picture in the field of kidney transplantation.

Kidney transplantation from an HIV-positive cadaveric donor.

Kidney transplantation is the gold-standard therapy for select HIV-positive patients with ESRD. Since the Italian Ministry of Health defined the guidelines for organ donation from HIV-positive persons in 2018, we report the first case of renal transplantation from an HIV-positive cadaveric donor in two HIV-positive recipients in Italy. The donor was a 50-year-old male, deceased due to post-anoxic encephalopathy, with a history of HIV infection in HAART, undetectable viral load, and HCV-related chronic hepatitis that had been previously treated. The first recipient was a 59-year-old female with a prior history of drug addiction, and she suffered from ESRD secondary to HIV nephropathy. The patient followed preoperative HAART with a good viral response and undetectable HIV viral load. She also had a history of HCV-related chronic hepatitis that had been successfully treated. The right kidney was uneventfully transplanted. The patient developed an asymptomatic reinfection of endogenous BK virus. The second recipient was a 41-year-old male with ESRD secondary to polycystic kidney disease. The patient was HIV-positive in HAART, with a good viro-immunologic response and an undetectable HIV viral load. He suffered from a severe form of hemophilia A and HCV-related chronic hepatitis, which had been previously treated with undetectable HCV RNA. The left kidney was uneventfully transplanted. At the end of follow-up, both patients had a healthy condition with stable renal function, a persistently good viral response and undetectable HIV and HCV viral loads. These encouraging preliminary results seem to confirm the safety and effectiveness of kidney transplantation from select HIV-positive donors.

Malaria blood safety policy in five non-endemic countries: a retrospective comparison through the lens of the ABO risk-based decision-making framework.

BACKGROUND: In non-endemic countries, malaria risk is addressed by selectively testing or deferring at-risk donors. These policy decisions were made using a variety of decision-making frameworks prior to the development of the Alliance of Blood Operators Risk Based Decision-Making Framework. It is unclear whether the range of items assessed in the decision-making process would be increased if the Framework were used. We compared assessments considered in France, England and Australia for decisions to implement selective testing, plus donor selection criteria (Canada and the USA included) with those recommended by the Framework. MATERIALS AND METHODS: Elements of the Framework were identified: the intervention, safety threat, availability threat, donor impact, financial implications, risk communication, stakeholder and regulatory aspects. Decisions about selective testing and donor selection criteria were analysed separately. Assessments were compared against elements of the Framework and the level of concern for considerations rated. RESULTS: Sufficiency of the blood supply (plus safety in France) were the drivers for selective testing; main trade-offs were high operational impact and cost. In three donor criteria examples, transfusion-transmitted malaria cases prompted the change. Social concerns were high in France and Australia, political/regulatory concerns influenced decisions in France, Australia and Canada, while sufficiency was a consideration in Canada and the USA. Decision trade-offs involved moderate operational impact. DISCUSSION: The assessments considered in each country were generally consistent with the assessments recommended by the Framework. When data supported quantified risk assessment, safety and operational feasibility had the greatest weight. When risk was not well defined, contextual factors such as social and political concern had greater weight.

Barriers to live and deceased kidney donation by patients with chronic neurological diseases: Implications for donor selection, donation timing, logistics, and regulatory compliance.

Live and deceased kidney donation by the numerous patients with advanced, progressive systemic neurological diseases, and other chronic neurological conditions (eg, high C-spine injury) remains largely unexplored. In a review of our current clinical practice, we identified multiple regulatory and clinical barriers. For live donation, mandatory reporting of postdonation donor deaths within 2 years constitutes a strong programmatic disincentive. We propose that the United Network for Organ Sharing should provide explicit regulatory guidance and reassurance for programs wishing to offer live donation to patients at higher risk of death during the reporting period. Under the proposal, live donor deaths within 30 days would still be regarded as donation-related, but later deaths would be related to the underlying disease. For deceased donation, donation after circulatory death (DCD) immediately following self-directed withdrawal of life-sustaining treatment ("conscious DCD") is not universally covered by existing DCD agreements with donor hospitals. Organ procurement organizations should thus systematically strive to revise these agreements. Obtaining adequate first-person consent from these communicatively severely impaired patients may be challenging. Optimized preservation and allocation protocols may maximize utilization of these DCD kidneys. Robust public debate and action by all stakeholders is necessary to lower existing barriers and maximize donation opportunities for patients with chronic neurological conditions.

Dissection and Preparation of Human Primary Fetal Ganglionic Eminence Tissue for Research and Clinical Applications.

Here, we describe detailed dissection and enzymatic dissociation protocols for the ganglionic eminences from the developing human brain to generate viable quasi-single cell suspensions for subsequent use in transplantation or cell culture. These reliable and reproducible protocols can provide tissue for use in the study of the developing human brain, as well as for the preparation of donor cells for transplantation in Huntington's disease (HD). For use in the clinic as a therapy for HD, the translation of these protocols from the research laboratory to the GMP suite is described, including modification to reagents used and appropriate monitoring and tissue release criteria.

[Bone banks : The state-of-the-art]. / Knochenbanken : State-of-the-Art.

Bone banks are responsible for the collection, production, testing, packaging, storage and delivery of osseous grafts. In compliance with legal and quality requirements, it is their main task to ensure the biological properties and the microbiological safety of the transplants as well. German legal requirements for bone banking are explained and current standards with respect to donor selection, laboratory tests and tissue processing, as well as labeling are discussed. Production and preparation procedures should include a validated microbiological inactivation method that largely preserves the biological properties of the tissue.

Harnessing Scientific and Technological Advances to Improve Equity in Kidney Allocation Policies.

We reported that current assignment of HLA-DQ is a barrier to organ allocation. Here we simulated the impact of incorporating HLA-DQ antigens and antibodies as A/B and αß allelic variants, respectively, on calculated panel reactive antibody (cPRA) and probability of finding potential compatible donors (PCD). A cohort of 1224 donors and 2075 sensitized candidates was analyzed using HLA-DQαß allelic (study) versus serologic (current practice) nomenclature. A significant (p < 10-4 ) decrease in cPRA was observed with higher impact for male versus female, and first transplant versus retransplant (p < 10-4 ), affecting mostly patients with moderate cPRA (30-80%). Consequently, the number of patients qualifying for 100% cPRA points according to the United Network for Organ Sharing-Kidney Allocation System decreased by 37%. More critically, by using allelic versus serologic nomenclature for HLA-DQ, the number of PCDs for all patients was increased, with male and first-transplant patients showing a higher expansion compared with female and retransplants. Patients of blood group O showed the highest benefit. The goal of reporting unacceptable antigens is to improve accuracy of virtual crossmatching and increase the likelihood of finding immunologically compatible donors. Our simulation provides strong support for the need to re-evaluate the use of allele typing and how HLA-DQ antigens and antibodies are incorporated into allocation policies to ensure equity.

An Exception to the Rule or a Rule for the Exception? The Potential of Using HIV-Positive Donors in Canada.

Selected human immunodeficiency virus (HIV)-infected patients with end organ failure can safely receive an organ transplant from an HIV uninfected donor. Recent demonstration of the short term safety of organ transplantation between HIV-infected persons prompted a change in US American law to allow such transplantations. Prompted by the recent completion of the first organ transplantation between HIV-infected persons in Canada, we review Canadian law regarding the use of organs from HIV-infected donors, estimate the number of potential HIV-infected donors in Canada, and critically review considerations related to advancing organ transplantation from HIV-infected donors in Canada. Existing legislation allows organ transplantation from an HIV-infected donor under exceptional medical circumstances and therefore no change in legislation is required to increase utilization of organs from HIV-infected donors for transplantation in Canada. Among 335,793 hospital deaths between 2005 and 2009 in Canadian provinces excluding Quebec, 39 potential HIV-infected donors were identified. The actual number of HIV potential donors is estimated to be approximately 60% lower (3-5 potential donor per year), if the absence of viremia is required for transplantation. Although offering all Canadians the opportunity to donate organs is a laudable goal, further research to understand the need for HIV-positive donors and the willingness of HIV-positive recipients to accept organs from HIV-positive donors is needed to inform future policy regarding organ donation from HIV-infected persons in Canada.

Global trends and challenges in deceased donor kidney allocation.

Worldwide, the number of patients able to benefit from kidney transplantation is greatly restricted by the severe shortage of deceased donor organs. Allocation of this scarce resource is increasingly challenging and complex. Striking an acceptable balance between efficient use of (utility) and fair access to (equity) the limited supply of donated kidneys raises controversial but important debates at ethical, medical, and social levels. There is no international consensus on the recipient and donor factors that should be considered in the kidney allocation process. There is a general trend toward a reduction in the influence of human leukocyte antigen mismatch and an increase in the importance of other factors shown to affect posttransplant outcomes, such as cold ischemia, duration of dialysis, donor and recipient age, and comorbidity. Increased consideration of equity has led to improved access to transplantation for disadvantaged patient groups. There has been an overall improvement in the transparency and accountability of allocation policies. Novel and contentious approaches in kidney allocation include the use of survival prediction scores as a criterion for accessing the waiting list and at the point of organ offering with matching of predicted graft and recipient survival. This review compares the diverse international approaches to deceased donor kidney allocation and their evolution over the last decade.