Title: Safe and appropriate use of blood components
Funder: Department of Health (England)

Abstract: Blood transfusion can be a life-saving intervention [1]. However unnecessary transfusions and unsafe transfusion practices expose patients to the risk of serious adverse transfusion reactions and transfusion transmitted infections as well as reducing the availability of blood products for patients who are in need [1].Nevertheless there is remarkably little evidence from randomised controlled trials on what types of patients benefit from blood transfusions what blood products should be transfused and how much patients should receive.This grant will enable our group (Systematic Review Initiative) to expand to meet the increasing demand for evidence in blood transfusion. The Systematic Review Initiative (SRI) is a clinical research group established by NHS Blood and Transplant (NHSBT - sole provider of blood products for England and North Wales) in 2002 and funded through the four UK Blood Services. It is based within NHSBTs Oxford Blood Centre at the John Radcliffe Hospital and has developed close links with both the hospital and the University of Oxford. The strategic aim of the Systematic Review Initiative (SRI) and this programme grant is to strengthen the evidence base of transfusion medicine by initiating supporting and disseminating systematic reviews (www.transfusionevidiencelibrary.com). This work is linked to the development of new clinical trials (TOPPS trial)[2] and underpinning and/or challenging recommendations for practice (changes to donor exclusion criteria)[3].National transfusion guidelines are often based on expert opinion rather than a firm evidence base. Our reviews are planned to provide the evidence base for when it is safe not to give blood components and also the best methods of reducing inappropriate use. This will reduce the risk to the future blood supply.The SRI is supported by an independent steering committee consisting of: clinicians (anaesthetist cardiac surgeon intensivist); National Blood Transfusion Committee representative and systematic review and research methodologists from the UK and Canada. A primary role of the steering committee is to identify topics and priorities for new systematic reviews.Since its inception the SRI has worked with several Cochrane Review Groups and has strong links with the Haematological Malignancies the Cystic Fibrosis and Genetic Disorders and Gynaecological Cancer Groups.Our reviews will identify the evidence required to determine when administration of blood components is appropriate and when to avoid their use. This will help to maintain the blood supply for the nation and ensure that patients are not exposed to unnecessary risks.The general themes within this proposal have been highlighted as important by NHS Blood and Transplant (NHSBT) the National Blood Transfusion Committee and external stakeholders (e.g. patient groups and charities).We have focused on two patient groups whose use of blood products is expected to increase:1) Patients with acquired haematological disorders2) Patients with haemoglobinopathiesThe incidence and prevalence of haemoglobinopathies and acquired haematological disorders is increasing. This is due to changes in the ethnic mix of the UK population (sickle cell disease is the commonest serious genetic disorder) an ageing population (cancer and myelodysplasia incidence rising) and improved management and treatment of patients with these disorders leading to increased life expectancy. Usage in other patient groups e.g. surgical patients is decreasing (due to improved surgical techniques and use of alternative agents e.g. tranexamic acid). Also both of these patient groups can receive large numbers of transfusions often over very prolonged periods they are therefore much more likely to develop complications from blood transfusions.In detail are reviews will consist of:RED BLOOD CELL(RBC) TRANSFUSION REVIEWS. Sickle cell disease(SCD) is the commonest serious genetic disorder in England and the number of babies born with SCD globally is expected to increase by 32% by 2050 [4]. Patients with SCD required RBC transfusions to treat and prevent complications but they are at increased risk of developing alloantibodies that can make it difficult and expensive to find future compatible RBC components. Currently there is great uncertainty about when RBC transfusions should and should not be given and our reviews will focus on these areas.PLATELET TRANSFUSION REVIEWS. Demand for platelet components has risen by 24% over the last ten years [56]; given this level of increase there is a significant risk to the future supply of platelet components [7]. This growing demand is due to an increase in the incidence and prevalence of haematological disorders. Approximately 60% of all platelet transfusions issued are given to haematology patients [8] and the commonest indication (69%) in this patient group is to prevent bleeding [9]. In the UK there has been an 11 to 14% increase in new cases of lymphoma and myeloma over last decade[10]. The UK population is ageing and the incidence and prevalence of myelodysplasia rises markedly with age[11]. The Department of Health has projected that the largest increase in blood component demand is for patients with myelodsyplasia (57% rise between 2012/13 and 2021/22)[12]. A third of our planned reviews will therefore focus on the use of platelet transfusions.FRESH FROZEN PLASMA(FFP) TRANSFUSION REVIEWS. Use of prophylactic FFP has been shown to be ineffective at preventing bleeding [13]. Physicians commonly administer FFP to “correct” a mild or moderate derangement in clotting results prior to an invasive procedure[14]. It is unclear whether this use of FFP has any beneficial effects. If our reviews showed no beneficial effects patients’ exposure to unnecessary blood products would be reduced.GRANULOCYTE TRANSFUSION REVIEWS. We will assess the effect and effectivness of granulocyte transfusions for the prevention and treatment of sepsis.TREATMENT OF TRANSFUSION COMPLICATIONS REVIEWS. Patients with thalassaemia and SCD can develop transfusional iron overload due to repeated RBC transfusions leading to severe complications due to liver and cardiac toxicity. This can be prevented by iron chelators. Howeverpatients often find these iron chelations therapies cause multiple side effects or have problems with the onerous chelation regimens required leading to reduced compliance. Our reviews will help to identify interventions that will improve compliance with these treatments.REDUCTION OF INAPPROPRIATE USE REVIEWS. Multiple national audits have shown that a significant proportion of blood components given are outside national guidelines[9]. However it has been shownthat changing physicians’ prescribing practices can be difficult[15]. We need to identify which interventions are the most effective and hence should be the practices implemented by the NHS. Blood components are expensive and limited resources. Any evidence that led to a reduction in blood component usage could have a significant impact on NHS costs. Within the UK 312000 units of platelets and 2.15 million units of red cells were issued last year at a total cost of £328 million [516]. According to recent national audits at least 20% of blood products were given outside national guidelines[8]. Any reduction in inappropriate usage due to evidence provided by our reviews would lead to a significant financial benefit.REFERENCES[1] WHO. Blood safety and availability Fact sheet N°279 2013. http://www.who.int/mediacentre/factsheets/fs279/en/[2] Stanworth et al. A no-prophylaxis platelet transfusion strategy for hematologic cancers. N Engl J Med 2013;368:1771-80.[3] Stainsby et al. Safety of blood donation from individuals with treated hypertension or non-insulin dependent type 2 diabetes – a systematic review. Vox Sang 2010;98(3):431–40.[4] Piel et al. Global burden of sickle cell anaemia in children under five 2010-2050:modelling based on demographics excess mortality and interventions.[5] Bolton-Maggs et al on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2012 Annual SHOT Report (2013).[6] Taylor et al on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2008 Annual SHOT Report (2009).[7] Williamson & Devine. Challenges in the management of the blood supply. The Lancet 2013;381:1866-75.[8] Pendry & Davies. An audit of the use and wastage in the North West of England and North Wales - where have all the platelets gone? . Blood and Transfusion Matters. 2011;34:17-19.[9] Estcourt et al. Platelet transfusions in haematology patients: are we using them appropriately? Vox Sang. Nov 2012;103(4):284-293.[10] Cancer Research UK 2013. Percentage Change in European Age-Standardised Three Year Average Incidence Rates Males UK 1999-2001 and 2008-2010 for the major types of haematological malignancies and all cancers excluding non-melanoma skin cancer.[11] Neukirchen et al. Incidence and prevalence of myelodysplastic syndromes; data from the Dusseldorf MDS-registry. Leukemia Research 2011;35:1591-6.[12] Andrew Parker Principal Operation Research Analyst Health Protection Analytical Team Department of Health[13] Yang et al. Is fresh frozen plasma clinically effective? An update of a systematic review of randomized controlled trials. Transfusion 2012 Aug; 52(8):1673-86.[14] Callum & Dzik. The use of blood components prior to invasive procedures: a critical appraisal. In: Transfusion Therapy: Clinical Principles and Practice. 3rd Ed. 2010.[15] Grimshaw et al. Changing physicians’ behaviour: what works and thoughts on getting more things to work. J Contin Educ Health Prof; 22(4):237-43.[16] NHSBT Price list 2013/2014. http://hospital.blood.co.uk/library/pdf/price_list_2013_14.pdf


Research activity codes: 6.4 SURGERY;6.1 PHARMACEUTICALS
Health categories: BLOOD