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Port Glasgow, United Kingdom

Stanworth S.J.,University of Oxford | Walsh T.S.,Royal Infirmary | Prescott R.J.,University of Edinburgh | Lee R.J.,University of Edinburgh | And 2 more authors.
Critical Care

Introduction: Fresh frozen plasma (FFP) is widely used, but few studies have described patterns of plasma use in critical care. We carried out a multicentre study of coagulopathy in intensive care units (ICUs) and here describe overall FFP utilisation in adult critical care, the indications for transfusions, factors indicating the doses used and the effects of FFP use on coagulation.Methods: We conducted a prospective, multicentre, observational study of all patients sequentially admitted to 29 adult UK general ICUs over 8 weeks. Daily data throughout ICU admission were collected concerning coagulation, relevant clinical outcomes (including bleeding), coagulopathy (defined as international normalised ratio (INR) >1.5, or equivalent prothrombin time (PT)), FFP and cryoprecipitate use and indications for transfusion.Results: Of 1,923 admissions, 12.7% received FFP in the ICU during 404 FFP treatment episodes (1,212 FFP units). Overall, 0.63 FFP units/ICU admission were transfused (0.11 units/ICU day). Reasons for FFP transfusion were bleeding (48%), preprocedural prophylaxis (15%) and prophylaxis without planned procedure (36%). Overall, the median FFP dose was 10.8 ml kg-1, but doses varied widely (first to third quartile, 7.2 to 14.4 ml kg-1). Thirty-one percent of FFP treatments were to patients without PT prolongation, and 41% were to patients without recorded bleeding and only mildly deranged INR (<2.5). Higher volumes of FFP were administered when the indication was bleeding (median doses: bleeding 11.1 ml kg-1, preprocedural prophylaxis 9.8 ml kg-1, prophylaxis without procedure 8.9 ml kg-1; P = 0.009 across groups) and when the pretransfusion INR was higher (ranging from median dose 8.9 ml kg-1at INR ≤1.5 to 15.7 ml kg-1at INR >3; P < 0.001 across ranges). Regression analyses suggested bleeding was the strongest predictor of higher FFP dose. Pretransfusion INR was more frequently normal when the transfusion indication was bleeding. Overall, posttransfusion corrections of INR were consistently small unless the pretransfusion INR was >2.5, but administration during bleeding was associated with greater INR corrections.Conclusions: There is wide variation in FFP use by ICU clinicians, and a high proportion of current FFP transfusions are of unproven clinical benefit. Better evidence from clinical trials could significantly alter patterns of use and modify current treatment costs. © 2011 Stanworth et al.; licensee biomed central ltd. Source

Thomas S.,NHS England | Turner M.L.,Scottish National Blood Transfusion Service | Williamson L.M.,NHS England
Transfusion Clinique et Biologique

Three cases of vCJD transmission by blood transfusion have been reported in the UK, and a fourth case discovered at post-mortem. Modelling has been conducted to predict the number of cases that may occur in the future through transfusion, based on estimates of prevalence, infectivity and susceptibility, and a number of steps have been taken to reduce the risk of transmission. These include deferral of previously transfused donors, leucocyte depletion of all components, importation of plasma for certain patient groups and for fractionation, and the collection of the majority of platelets from single donors (by apheresis). However, even with these interventions, some future cases are still predicted. The UK-wide Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) considers the evidence for clinical and cost-effectiveness of any proposed intervention, such as prion assays and filters, and makes recommendations to the governments of the UK. The development of prion assays is challenging as prions do not generate an immune response, do not have nucleic acid and are present in blood in very low concentrations against a high background of normal prion protein. It is critically important that prion assays show high levels of sensitivity and -especially-specificity for a healthy blood donor population. Assessment is impacted by the very short supply of positive human samples, necessitating the use of animal models. Filters that are capable of removing prions from blood components have been developed and CE marked, but it is again necessary to use animal models to study their efficacy. Guidelines have been produced for the assessment of the quality of red cells filtered through these devices, and a clinical safety study has recently been completed. In conclusion, the evaluation of screening assays and prion filters is challenging, time-consuming and costly, but these evaluations are critical to policy making. © 2013 Elsevier Masson SAS. Source

Galea G.,Scottish National Blood Transfusion Service
Transfusion Medicine and Hemotherapy

Background: The Scottish National Blood Transfusion Service (SNBTS) is the main provider of tissues in Scotland. Tissue collection programmes were established in the mid-1990s, and the range of tissues collected has increased progressively over the years. Methods: Whilst the majority of tissues are obtained from cadaveric donations, bone is collected only from living donors who are usually patients undergoing primary hip replacement surgery (surgical donors). The bone is collected in an operating theatre, and, once stored, no further processing takes place prior to issue. Bone that fails for any reason (quality, microbiology or virological nonnegative result) is discarded. Results: The deferral rate amongst live surgical bone donors in Scotland is around 65%, and it has been slowly and progressively rising from around 55% over the past few years. This needed investigated, particularly because comparisons with blood donors show that the deferral rate amongst bone donors is more than double that of first-time blood donors (29.7%). Our processes and systems are standardised, and our cohort of bone bank nurses have all been similarly trained and competency assessed. Moreover our data collection was done in a uniform fashion. It was therefore possible to conduct a 6-year audit on bone donor deferrals. It was found that a history of transfusion (16%), history of malignancy (18%) and bone quality (26%) were the main reasons for bone donor deferrals, accounting for 60% of all deferrals. Conclusions: When these are taken into account, the residual deferral rates become very similar numerically to blood donors. It is important to note however that there are significant differences between the blood and bone donor cohorts. This study also highlighted some of deferral reasons. Particularly malignancy is a cause of significant numbers of deferrals, and the evidence of transmissibility of malignancy through bone donation is not strong. More robust risk assessments should be undertaken prior to implementing deferral conditions. © 2011 S. Karger AG, Basel. Source

Chalmers J.D.,University of Dundee | McHugh B.J.,Queens Medical Research Institute | Doherty C.,University of Edinburgh | Smith M.P.,Royal Infirmary | And 3 more authors.
The Lancet Respiratory Medicine

Background: Mannose-binding lectin (MBL) is a key component of innate immunity. MBL deficiency is common (10-30% of the general population depending on the definition used) and has been associated with disease progression in cystic fibrosis. We aimed to assess the effect of MBL deficiency on disease severity in non-cystic fibrosis bronchiectasis. Methods: We recruited patients with non-cystic fibrosis bronchiectasis and age-matched and sex-matched controls at a specialist bronchiectasis clinic in Edinburgh, UK. We assessed MBL function with genotyping (low-expressing genotype [deficiency] defined as homozygosity for exon 1 mutations [YO/YO] or compound heterozygosity [XA/YO]; YA/YO and XA/XA genotypes were defined as intermediate-expressing with all other genotypes defined as high-expressing) and serum measurements (deficiency defined with two parameters: <500 ng/mL or <200 ng/mL). We assessed rates of exacerbation, chronic bacterial colonisation, and lung function during 4 years of follow-up. Findings: We included 470 patients with bronchiectasis and 414 controls. MBL genotype frequencies and MBL serum concentrations did not differ between patients and controls. 55 (12%) patients with bronchiectasis had low-expressing genotypes. These patients had a mean of 2·7 exacerbations per year (SD 1·8), compared with 1·9 per year (1·2) for 135 patients with intermediate-expressing genotypes and 1·9 per year (1·3) for 280 patients with high-expressing genotypes (p<0·0001). Chronic colonisation with bacteria was most frequent in patients with low-expressing genotypes (47 [85%] patients vs 82 [61%] patients with intermediate-expressing genotypes and 183 [65%] patients with high-expressing genotypes; p=0·0041); especially P aeruginosa colonisation (19 [35%] patients vs 13 [10%] patients and 36 [13%] patients; p<0·0001). Patients with low-expressing genotypes were more likely to be admitted to hospital for severe exacerbations during follow-up (27 [49%] patients vs 42 [31%] patients and 87 [31%] patients; p=0·032). Patients with low-expressing genotypes also had increased scores for radiological severity and worse quality of life compared with the other two groups. MBL serum deficiency (<200 ng/mL) was associated with increased exacerbations, hospital admissions, and radiological severity. When <500 ng/mL was used as the definition of deficiency, the associations with exacerbation frequency and radiological severity were no longer significant. Interpretation: MBL might be an important modifier of disease severity in non-CF bronchiectasis. Funding: UK Medical Research Council, UK Chief Scientists Office. © 2013 Elsevier Ltd. Source

Galea G.,Scottish National Blood Transfusion Service
Essentials of Tissue Banking

Presents much-needed, up-to-date information on essential scientific aspects of tissue banking Incorporates new regulations and risk-assessment requirements into tissue banking methodologies Meets a significant need in a time of rapid change in tissue bankin Tissue banking is undergoing a paradigm shift. There are now a plethora of guidance and regulatory documents, in response to recent regulation. There is however, relatively little information on the scientific and technical principles on routine tissue banking practices. The information that exists is relatively old and in somewhat obscure journals. This book attempts to provide a coherent and up to date approach. Each author, who is a recognized expert in their field, was asked to illustrate the processes involved in modern tissue banking practices. Where these are based on evidence and science, they were asked to explain this in a clear and concise manner. Where evidence it is not available, the authors were asked to provide the reasons why they believe practices have developed the way they have. This could range from the precautionary principle, custom and practice, common sense approach etc. This book has been split into 5 sections: Management of donors and the banking of common tissues and cells, principles of storage and processing of tissues, ensuring safety of the products by testing the donor, the tissue and the environment, ensuring quality of the products by establishing a quality system and an IT infrastructure and the Regulatory and ethical environment in which we operate. Although it is possible to bank all types of cells, including stem cells, these are not covered in this book. The organisation and target audiences for stem cells are quite different from those of tissues. Cord blood banking, on the other hand is very similar and they have therefore been included. The intention of this book is to cover the basis of current practices, rather than future developments, such as embryonic cell developments, tissue engineering and gene therapy. These are more akin to cellular therapies. Although they share many banking similarities to tissues, their inclusion in this book would have made it too cumbersome. © 2010 Springer Science+Business Media B.V. All rights reserved. Source

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