National Health Service Blood Research Articles

What Is the Maximum Time That a Unit of Red Blood Cells Can Be Safely Left Out of Controlled Temperature Storage?

What Is the Maximum Time That a Unit of Red Blood Cells Can Be Safely Left Out of Controlled Temperature Storage?

Informed consent and patient understanding of blood transfusion

Obtaining separate informed consent for blood transfusion is mandatory in some countries. Although patients should be informed about risks and benefits of transfusion, studies suggest this does not happen routinely in the UK and the patient perspective is lacking in the current literature. To explore provision of information and the consent process for patients receiving blood transfusions at our hospital. To assess patient recall of the consent process, information conveyed, ease in understanding discussions and perceived knowledge of transfusion afterwards. All 342 adult patients for whom blood was cross-matched between 1 March 2008 and 30 April 2008 were sent postal questionnaires. One hundred and sixty-four questionnaires were returned. Overall, 59·1% of patients said someone explained they might need a transfusion; of those 86·7% felt the reason had been explained. Only 58·8% of patients felt informed of what transfusion involves, with 67·0% told of the benefits and 27·8% informed of risks. Overall, 51·5% of patients said this information was easy to understand, but only 26·8% were aware of a transfusion information leaflet. Of those receiving leaflets, all said they read it and had no questions. Despite this, 61·9% were satisfied overall with the information received. Information leaflets could increase the information available to patients, with minimal impact on health care professionals' time. Leaflets are available, free of charge, from the National Health Service Blood and Transplant website. These have been introduced at each bedside, in pre-op packs and in outpatient clinics, with re-assessment planned in 6 months.

Interventions Implemented to Reduce the Risk of Transmission of Bacteria by Transfusion in the English National Blood Service

Background: Bacterial contamination remains a significant problem in transfusion medicine. A National Health Service Blood and Transplant (NHSBT) study and surveillance data indicated skin commensals derived from the skin of the donor are the major contaminants of blood components. NHSBT therefore explored two interventions: improved donor arm disinfection and diversion. Methods: Improved donor arm disinfection: Commercial and in-house methods of disinfection were evaluated. Swabs at the venepuncture site were taken before and after disinfection and the reduction in bioburden determined. Diversion: Special collection bags were manufactured to allow the initial volume of blood to flow into a pouch, representing the diversion pouch and then the next flow of blood into another pouch representing the collection bag. Pouches were screened for the presence of bacteria. The reduction in bacterial contamination was then determined. Results: A two-step commercial procedure (Donor Prep Kit; DPK) consisting of 70% isopropyl alcohol followed by tincture of iodine was shown to be a best practice procedure (2-min procedure). A 99.79% reduction was obtained, and this method was 10 times more effective than current practice at that time. The DPK was shown in a field trial to increase donor waiting time. A second study was initiated to find a more rapid procedure. ChloraPrep®, consisting of 2% chlorhexidine gluconate and 70% isopropyl alcohol, was shown to have equivalent disinfection efficiency as the DPK, but only took 1 min to perform. In 2006, ChloraPrep was introduced as the national method of donor arm disinfection. Diversion was shown to give a 47% reduction in contamination and was introduced nationally in 2002. Conclusion: Improved donor arm disinfection and diversion are effective, low-cost interventions, but do not eliminate all bacterial transmissions. In 2011, bacterial screening of platelet components was introduced by NHSBT to further increase the safety of the blood supply.

The acute management of trauma hemorrhage: a systematic review of randomized controlled trials

IntroductionWorldwide, trauma is a leading cause of death and disability. Haemorrhage is responsible for up to 40% of trauma deaths. Recent strategies to improve mortality rates have focused on optimal methods of early hemorrhage control and correction of coagulopathy. We undertook a systematic review of randomized controlled trials (RCT) which evaluated trauma patients with hemorrhagic shock within the first 24 hours of injury and appraised how the interventions affected three outcomes: bleeding and/or transfusion requirements; correction of trauma induced coagulopathy and mortality.MethodsComprehensive searches were performed of MEDLINE, EMBASE, CENTRAL (The Cochrane Library Issue 7, 2010), Current Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) and the National Health Service Blood and Transplant Systematic Review Initiative (NHSBT SRI) RCT Handsearch Database.ResultsA total of 35 RCTs were identified which evaluated a wide range of clinical interventions in trauma hemorrhage. Many of the included studies were of low methodological quality and participant numbers were small. Bleeding outcomes were reported in 32 studies; 7 reported significantly reduced transfusion use following a variety of clinical interventions, but this was not accompanied by improved survival. Minimal information was found on traumatic coagulopathy across the identified RCTs. Overall survival was improved in only three RCTs: two small studies and a large study evaluating the use of tranexamic acid.ConclusionsDespite 35 RCTs there has been little improvement in outcomes over the last few decades. No clear correlation has been demonstrated between transfusion requirements and mortality. The global trauma community should consider a coordinated and strategic approach to conduct well designed studies with pragmatic endpoints.

A pilot to examine the logistical and feasibility issues in testing deceased tissue donors for vCJD using tonsil as the analyte

Transplanted tissues have transmitted transmissible spongiform encephalopathies and in the UK there have been more cases of variant Creutzfeldt-Jakob disease (vCJD) than elsewhere in the world. A pilot study was undertaken to look at the feasibility of testing for vCJD in deceased donors using tonsillar tissue. This pilot showed that obtaining consent for removal and testing tonsil tissue was feasible. Donor eligibility for inclusion in the pilot was limited to tissue donors from the National Health Service Blood and Transplant, Tissue Services and to donors shared with the Corneal Transplant Service Eye Banks. Obtaining tonsillar tissue in the immediate post-mortem period was limited by the presence of rigor mortis. Tonsillar tissue was suitable for routine analysis for the presence of prion associated with vCJD in deceased tissue donors. Production and processing of tissue was straightforward and a low assay background was obtained from most samples. Since palatine and lingual tonsil tissue can be obtained in pairs it was possible, in the majority of cases, to set aside an intact sample for confirmatory testing if required. In one instance a sample was reactive by Western blot. However, the pattern of reactivity was not typical for that obtained from vCJD patients. Unfortunately the sample was not of sufficient quality for the confirmatory test to provide a conclusive result.

Analysis of factors that affect outcome after transplantation of kidneys donated after cardiac death in the UK: a cohort study

Analysis of factors that affect outcome after transplantation of kidneys donated after cardiac death in the UK: a cohort study

Exclusion of deceased donors post-procurement of tissues

The EU Tissues and Cells Directive (2004/23/EC, 2006/17/EC, 2006/86/EC) (EUTCD) provides standards for quality and safety for all aspects of banking of tissues and cells for clinical applications. Commission Directive 2006/17/EC stipulates that the complete donor record with all the medical information is assessed for suitability before releasing tissues for clinical use. The aim of this study was to investigate the medical reasons for post-procurement donor exclusion, to identify the various potential sources for gathering information about donors' medical and behavioural history and to evaluate their contribution to maximising the safety of donations. Information was collected from the Tissue Services (TS) records of 1000 consecutive deceased donors submitted to National Health Service Blood and Transplant (NHSBT) medical officers for authorisation for release for subsequent tissue processing and then for transplantation. Of the 1000 donors 60 (6%) were excluded because they did not fulfil the donor selection requirements of the EUTCD and NHSBT donor selection guidelines. The main reasons for medical exclusion were the presence of significant local or systemic infection in 32 donors (53% of those excluded for medical reasons) and a history of past or occult malignancy in 9 donors (15% of those excluded for medical reasons) which was not identified prior to procurement. The information leading to post-procurement exclusion was obtained from autopsy reports in 35 of the 60 excluded donors for medical reasons (58%) and from the general practitioner for 10 donors (17% of those excluded for medical reasons). In summary, careful evaluation of complete donor records reduces the potential risk of disease transmission by tissue allografts and ensures compliance with regulations and guidelines. The findings may lead to changes in donor selection policies with the aim of improving efficiency without compromising safety.

Qualification of serological infectious disease assays for the screening of samples from deceased tissue donors

Whilst some of the assays used for serological screening of post-mortem blood samples from deceased tissue donors in some countries have been specifically validated by the manufacturer for this purpose, a significant number of those currently in use globally have not. Although specificity has previously been considered a problem in the screening of such samples, we believe that ensuring sensitivity is more important. The aim of this study was to validate a broader range of assays for the screening of post-mortem blood samples from deceased tissue donors. Six microplate immunoassays currently in use within National Health Service Blood and Transplant (NHSBT) for the screening of blood, tissue and stem cell donations were included. Representative samples from confirmed positive donors were titrated in screen negative post-mortem samples in parallel with normal pooled negative serum to determine if there was any inhibition with the post-mortem samples. There were no significant differences seen (P<0.005) between the dilution curves obtained for the positive samples diluted in post-mortem samples and normal pooled sera. Although small numbers of samples were studied, it can be surmised that the post-mortem blood samples from deceased tissue donors, collected according to United Kingdom guidelines, are a suitable substrate for the assays evaluated. No diminution of reactivity was seen when dilution with sera from deceased donors was compared to dilution using pooled serum from live donors. In the absence of genuine low titre positive post-mortem samples, the use of samples spiked with various levels of target material provides a means of qualifying serological screening assays used by NHSBT for the screening of post-mortem blood samples from deceased tissue donors.

Age, alcohol and liver transplantation

Sir, Two recent cases of young men with severe alcoholic hepatitis, who were not offered a transplant, have highlighted some of the difficult decisions that have to be made in the field of liver transplantation.1,2 Although not all relevant medical information was available in the public domain, these two cases generated considerable and sometimes ill-informed public debate about the issues surrounding organ allocation and withholding of life-saving treatment from young men. In the UK, criteria for patient selection and organ allocation are developed within national health service (NHS) Blood and Transplant (NHSBT) by clinicians in consultation with patients and other health care professionals; and, as donated organs are considered a national resource, protocols are applied nationally to ensure the optimal balance of utility and equity. Cirrhosis, secondary to alcohol, raises controversies not seen with other indications because it is construed to be self-inflicted despite the existence of strong genetic and environmental factors. Indeed, patient outcome is better than some other indications, such as hepatitis C and hepatocellular carcinoma,3 and there are no significant differences in compliance or levels of re-employment in comparison to patients grafted for other conditions.3 Understandable concerns do remain about relapse in these patients; although …

Lot release testing of serological infectious disease assays used for donor and donation screening

Monitoring of the ongoing performance of infectious disease screening assays is a critical part of any donation screening programme. Although assay sensitivity is formally evaluated prior to implementation, it is essential that this level of performance is maintained from lot-to-lot. In 2002, National Health Service Blood and Transplant developed and implemented a formal system for the lot release testing of serology infectious disease screening assays. Lot release panels were prepared for each of the serological screening markers. They each comprise 10-15 members and include both genuine low-titre and diluted high-titre materials. For each panel member, a minimum reactivity is expected, based upon the formal sensitivity evaluation of each assay. All new lots of the screening assays used are assessed prior to supply of the lot to the organization. Since 2002, a total of 887 different lots of the serology screening assays used have been supplied. Of these, 876 (98.8%) passed lot release and were authorized for supply to the organization. Eleven lots (1.2%) were failed because the lots did not meet the release criteria or were unsuitable for some other reason. The lot release system has proved to be effective in objectively assessing assay performance to ensure that there is no significant lot-to-lot variation such that the performance of the assay may fall below that originally determined at evaluation. The few assays that have failed lot release did have proven performance issues that were subsequently accepted by the manufacturers. CONTENTS SUMMARY: Description of the Lot Release Testing system for serology infectious disease screening assays in use within NHSBT with a critical analysis and review of the data generated in the 7 years that the system has been in use.

Practical guidelines for applying statistical process control to blood component production

Legislation, guidelines and recommendations for blood components related to statistical process control (SPC) and the selection of a quality monitoring (QM) sampling regimen are subject to misinterpretation and lack practical guidance on implementation. The aim of this article is: to review and interpret applicable European legislation and guidelines and to develop an SPC strategy that meets these requirements; and to provide practical guidance on the selection and application of appropriate techniques and the interpretation of resultant blood component QM data. A methodology is presented which utilizes: an algorithm to select an appropriate quality-monitoring strategy for the blood component parameter under consideration; a range of straightforward, validated SPC techniques for variable data and an assessment of process capability (Cpk) and blood component parameter 'criticality' to determine the sampling regimen. The methodology was applied to routine National Health Service Blood and Transplant (NHSBT) blood component data for 2005-2006. Cpk values ranged from 0.22 to >3 and their predicted non-conformance rates were close to those observed (23 to <0.001%). Required sample size ranged from 0.01 to 10%. Chosen techniques identified significant deviation from 'as validated' performance within an appropriate time-scale. Thus the methodology was straightforward to apply and prompted the choice of a clinically and operationally appropriate sampling regimen and analysis for each blood component parameter. This evidence-based, targeted use of SPC for blood component monitoring provides an essential focus on processes with a low capability in achieving their specifications.

Towards better blood transfusion – recruitment and training

Recent national initiatives in blood transfusion safety in the UK have created the need for an expansion in haematologists subspecializing (wholly or in part) in transfusion medicine. In 2008, there are 62 transfusion consultants in the UK, but only 42 are full time, and only 19 have hospital sessions. Despite the need for expansion, recruitment appears difficult. The English blood transfusion service, National Health Service Blood and Transplant (NHSBT), is undergoing major reconfiguration, and the current practice of transfusion training for haematology specialists primarily at blood centres with little or no hospital training is not sustainable or desirable. Delivering a high-quality transfusion programme to haematology trainees is best achieved through an increased emphasis on hospital-based training. Improved research opportunities, joint NHSBT/hospital posts and a separate subspecialty training curriculum may stimulate interest in transfusion medicine.

Late Humoral Rejection in a Compliant ABO-compatible Liver Transplant Recipient

Humoral rejection (HR) is an immunological complication of solid organ transplantation but whose role in liver transplantation (LT) is debated. We present a case that fulfils all of the criteria required for the diagnosis of HR: donor-specific antibody (DSA), C4d deposition, tissue pathology, and evidence of organ dysfunction (1). In March 2001, a 36-year-old female was transplanted for fulminant seronegative liver failure, receiving a blood-group matched whole deceased donor graft from a 20-year-old donor. Initial immunosuppression was with tacrolimus-based triple therapy (azathioprine 75 mg and prednisone 20 mg). Her postoperative course over three years was unremarkable and, as she was overtly compliant with tacrolimus, the azathioprine was reduced and steroids stopped. Four years postLT, she was admitted to a local hospital with itch and clinical jaundice. Liver biopsy demonstrated acute severe rejection with a tacrolimus level of 7.9 ng/dl (Fig. 1, biopsy 1). Mycophenolate mofetil (2 g/day) and oral steroids were commenced. On admission to our institution liver biochemistry continued to deteriorate (day 1 bilirubin 181, alanine aminotransferase [ALT] 1267, alkaline phosphate 333; Figure 1) and bolus methylprednisone (500 mg iv bd) was instituted without biochemical response. Repeat liver biopsy demonstrated ongoing moderate cellular rejection, bile duct atypia but no evidence of bile duct loss (biopsy 2). Despite further steroid augmentation, no improvement was seen (biopsy 3). Human leukocyte antigen (HLA) antibody testing performed using Luminex technology identified an allogenic donor specific HLA-DR52 antibody, which was not present peri-LT.FIGURE 1.: The response of liver function tests (LFTs) to therapy. On admission (day 1, December 2006), LFTs were significantly deranged compared with December 2004. Class II HLA antibody titers (median fluorescence index), alkaline phosphatase (Alk Phos, iu/l), alanine aminotransferase (ALT, iu/l), bilirubin (μmol/L). In March 2006 (one month after discharge), LFTs were stable. Arrows or boxes represent treatments given. Numbers represent biopsies. Biopsy 1: Severe acute cellular rejection (ACR) (+++) with bile duct atypia (BDA). Biopsy 2: moderate ACR (++) with BDA, no sign of ductopenia. Biopsy 3: persistent moderate ACR (++), centrilobular necro-inflammation (CNI), no evidence of bile duct loss. Biopsy 4: mild ACR (+), BDA and CNI improved. Biopsy 5: ACR resolved, BDA and CNI not seen.Further treatment with plasmapheresis, intravenous immunoglobulins and rituximab produced a significant transient biochemical response, but no histological change (biopsy 4) and biochemical rebound after seven days. However, antithymocyte globulin (ATG) induced a sustained biochemical improvement and a significant reduction in the inflammatory infiltrate. At review and rebiopsy, a month later, the patient was clinically well, the HLA-DR52 antibody was absent and the cellular rejection had resolved (biopsy 5). Retrospective immunostaining of three biopsies was positive for C4d in small portal vessels and no class I, auto, or viral antibodies were detected on serology. Late HR is uncommon (approx. 5% [2]) and has been associated with previous rejection episodes (2) and noncompliance (3). Humoral mechanisms have been implicated in the pathogenesis of bile duct loss and arteriopathy in chronic rejection (4). Some histological features of chronic rejection were seen in this case (Fig. 1, bile duct atypia and centrilobular necroinflammation); however, ductopenia was not seen and the graft dysfunction was successfully reversed. Rituximab and plasmapheresis have proven to be effective in the prevention and treatment of early HR associated with DSA against ABO antigens (5, 6). These naturally occurring immunoglobulin M antibodies are produced by T-cell-independent B1 cells (7). In our case, the HLA class II specific DSA only showed a lasting response to a combination of therapies targeting multiple arms of the specific immune system, suggesting this HR was “driven” by activated alloreactive T-cells. Late rejection in LT, unlike other organs, is not invariably associated with a poor prognosis after successful treatment (2, 3) and the outlook for this patient is hopeful. Colin H. Wilson Kosh Agarwal David Talbot Brian C. Jaques Derek M. Manas The Liver Transplant Unit The Freeman Hospital Newcastle-upon-Tyne, United Kingdom Vaughan Carter Tissue Typing Laboratory National Health Service Blood and Transplant Newcastle-upon-Tyne, United Kingdom Alastair D. Burt The Department of Histopathology Royal Victoria Infirmary Newcastle-upon-Tyne, United Kingdom Stefan Hübscher Department of Pathology University of Birmingham Birmingham, United Kingdom