Effective serological and molecular screening of deceased tissue donors.

A comprehensive and effective screening programme is essential to support the banking of tissues from deceased donors. However, the overall quality of the samples obtained from deceased donors, quantity and condition, is often not ideal, and this may lead to problems in achieving accurate and reliable results. Additionally a significant percentage of referrals are still rejected upon receipt as unsuitable for screening. We are actively involved in improving the overall quality of deceased donor screening outcomes, and have specifically evaluated and validated both serological and molecular assays for this purpose, as well as developing a specific screening strategy to minimise the specificity issues associated with serological screening. Here we review the nature and effectiveness of the deceased donor screening programme implemented by National Health Service Blood and Transplant (NHSBT), the organisation with overall responsibility for the supply of tissue products within England. Deceased donor screening data, serological and molecular, from August 2007 until May 2012 have been collated and analysed. Of 10,225 samples referred for serology screening, 5.5 % were reported as reactive; of 2,862 samples referred for molecular screening, 0.1 % were reported as reactive/inhibitory. Overall 20 % of the serological and 100 % of the molecular screen reactivity was confirmed as reflecting true infection. The use of a sequential serology screening algorithm has resulted in a marked reduction of tissues lost unnecessarily due to non-specific screen reactivity. The approach taken by NHSBT has resulted in the development of an effective and specific approach to the screening of deceased tissue donors.

Tissue and corneal donation and transplantation in the UK.

NHS Blood and Transplant (NHSBT) was established in 2005 as a Special Health Authority when the National Blood Authority and UK Transplant merged. This helped to bring tissue banking and organ transplantation services under one umbrella organization. This merger means that ~!95% of all deceased donors (whether tissue, organ or both) are now facilitated by one organization. NHSBT Tissue Services is the largest tissue establishment in the UK, and is a multi-tissue bank that specializes in the consent, retrieval, processing, storage, and dispatch of donated tissue coordinated from a purpose built, state-of-the-art tissue bank in Liverpool. Tissue donations can come from either tissue-only donors or solid organ donors who also donate tissue. Annually there are ~450 multi-tissue donors and 2500 eye donors in the UK, resulting in many thousands of transplants, including 3564 cornea transplants in 2010-2011. The separation of tissue- and organ-specific donors is largely artificial, and while organ transplantation can be life-saving, tissue transplantation can also have a dramatic effect on a patient's quality of life. It is hoped that all donors, both organ and tissue, will be recognized for the gift they make to society after their death.

The serological screening of deceased tissue donors within the English Blood Service for infectious agents--a review of current outcomes and a more effective strategy for the future.

BACKGROUND AND OBJECTIVES: The overall effectiveness of the NHSBT screening programme for infectious agents in deceased tissue donors is examined and evaluated in terms of current outcomes and how to improve upon these outcomes. MATERIALS AND METHODS: The screening results and any subsequent confirmatory results from a total of 1659 samples from NHSBT deceased donors referred to NTMRL for screening for infectious agents were included in the analysis. RESULTS: Overall 1566/1659 (94.4%) of the samples were screen negative. A total of 93 were repeat reactive on screening for one or more of the mandatory markers screened for, of which only 12 (13%) were subsequently confirmed to be positive on confirmatory testing. The majority of the repeat reactive samples were demonstrating non-specific reactivity with the screening assays in use. CONCLUSION: Overall, the NHSBT screening programme for infectious agents in deceased tissue donors is very effective with a relatively low overall loss of donors because of non-specific reactivity. However, unnecessary loss of tissue products is not acceptable, and although this programme compares favourably with the outcomes of other such programmes, the confirmatory results obtained demonstrate both the need and the potential for improving the outcomes. This is particularly important as one donor may donate more than one product, and can be achieved very easily with a change to the screening algorithm followed, using the confirmatory data obtained to support and validate this change. CONTENTS SUMMARY: Critical analysis of the NHSBT screening programme for infectious agents in deceased tissue donors and a strategy involving the design and use of a different screening algorithm to improve these outcomes.

An evaluation of the capacity of differently prepared demineralised bone matrices (DBM) and toxic residuals of ethylene oxide (EtOx) to provoke an inflammatory response in vitro.

Demineralised bone matrix (DBM) is a form of allogeneic tissue graft widely used in oral and maxillofacial procedures. There is a long history of controversy relating to the suitability of ethylene oxide gas (EtOx) as a terminal sterilisation agent for this graft, relating to its effects on the clinical performance of the grafts. Furthermore, the generation of a toxic residual chemical (ethylene chlorohydrin, ECl) during the ethylene oxide sterilisation of patellar tendon allografts has been implicated in the failure of these grafts owing to the induction of a localised inflammatory response. In this study we have investigated the capacity of a range of different DBM preparations, and ECl dilutions, to induce the production of three pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and tumour necrosis factor alpha (TNF-alpha) from human peripheral blood mononuclear cells (PBMNCs). The levels of EtOx and ECl in EtOx terminally sterilised DBM and mineralised bone grafts were measured by gas chromatography. It was found that the only factor capable of rendering DBM pro-inflammatory was the presence of small (<20 micrometre diameter) DBM particles. No other processing or sterilisation technique resulted in the DBM becoming pro-inflammatory. Although it was also found that DBM, when EtOx-sterilised, retained more ECI than mineralised bone grafts following a standard EtOx sterilisation protocol, ECl did not provoke an inflammatory response in vitro at levels up to and including those which are cytotoxic to PBMNCs.