Guidelines for policies on alternatives to allogeneic blood transfusion. 1. Predeposit autologous blood donation and transfusion

This is the first of a series of newly prepared guidelines on alternatives to allogeneic blood transfusion. Further guidelines including the use of cell salvage and of pharmacological approaches to blood conservation will be published in due course. Decades of clinical application demonstrate that it is quite feasible to auto-transfuse blood that has been collected and stored for an interval of up to 6 weeks in standard storage media, and that up to three standard collection volumes (approximately 500 mL) can be collected from normal-sized adults (over 50 kg) during that interval. Furthermore, systems have been developed to reduce risk to participants and to boost haemoglobin (Hb) production during and after the procedure. However, such ‘pre-operative autologous donations’ (PAD) are not without risk, are of low clinical efficacy and are poorly cost-effective for the vast majority of patients in the UK. These guidelines update those previously issued by the BCSH and do not recommend the practice and use of PAD unless the clinical circumstances are exceptional. They also give an update on the legal regulatory circumstances pertaining to the UK following recent European Directives. Searches were carried out on Medline and PubMed using the following terms: autologous, blood transfusion, pre-operative, predeposit, EPO, iron, cardiac surgery, elderly, children, orthopaedics, directive and regulations. The recent European and UK legislations have also been scrutinized. The definitions of the types of evidence and the grading of recommendations used in this guideline originate from the US Agency for Health Care Policy and Research and are set out in the following Tables. Statements of evidence Grades of recommendations These guidelines comment on and update the policies for predeposit autologous blood donation and subsequent transfusion of the stored component described in the previous BCSH Guideline (1993). The terms predeposit autologous blood donation (PABD) and PAD refers to the collection and subsequent storage of blood in a manner similar to the collection and storage of blood from healthy unremunerated volunteers donating for general use except that the person from whom the blood is collected is intended also to be the recipient, the whole process being planned for the clinical benefit of that person by covering an expected loss of a significant amount of blood resulting from, for example, elective surgery. Although the term ‘donation’ in the autologous setting runs counter to logic, its use for this purpose has been widely accepted and will be continued where appropriate in the rest of this guideline, usually in the acronym PAD. The 1993 Guidelines referred specifically to blood ‘that is stored at 4 °C in CPD A1 for up to 35 days or in an optimal additive solution up to 42 days’ and covered many practical aspects including model proformas for obtaining referral letters obtaining consent labelling the packs collecting the blood. This included: timing (minimum intervals of a week and the ultimate collection 4 days before surgery) volume (no more than 12% estimated blood volume at each collection) oral iron therapy for all PAD patients They also stressed that PAD was only suitable for a minority of patients, principally those who could be expected to benefit from standard transfusion policies directed by ‘maximum surgical blood ordering schedule’ recommended that application should accord to a standard operating procedure, which would include an assessment of fitness to donate advised that patients infected with hepatitis B, hepatitis C or HIV/AIDS be excluded recommended minimum Hb concentrations of 110 g L−1 blood for men and women stated that the use of erythropoietin to encourage haemopoiesis ‘remains unclear’ referred to PAD in children, smaller adults and pregnant women recommended cardiological advice for patients with heart disease or receiving beta blockers or angiotensin-converting enzyme inhibitors recommended no PAD for patients with a history of epilepsy stressed that other ways of avoiding allogeneic transfusion should always be considered as an aside, specifically did not recommend directed donation. The 1993 Guidelines were prepared at a time when PAD was generally favourably and even enthusiastically undertaken in some quarters. For example, Isbister (1991) compared allogeneic – then often called ‘homologous’– transfusion with bank loans, which were easier to get, whereas PAD was analogous to the implicitly more worthy but harder work of saving money up for oneself. Hardy et al. (1994), who advocated the use of erythropoietin in PAD, stated that PAD ‘must become an integral part of strategy for centres where cardiac surgery is performed’. However, more recent opinion has been somewhat more guarded. Regulations regarding PAD ‘collection’ are now covered by Directives from the European Commission and the UK Blood Safety Regulations 2005, which are legally binding. The ‘clinical use’ of PAD blood is not so regulated, being subject more to professional judgement as to clinical need: this will also be covered in these Guidelines, particularly where practice has changed and parts of which are now legally regulated. These Guidelines, which should be shared with patients who request or enquire after this form of transfusion therapy, are aimed at and have been approved by Clinicians who may wish to undertake this form of therapy Senior representatives of blood establishments in the UK and Hospital blood banks considering applying for valid appropriate authorization. These Guidelines deal almost entirely with the collection, testing, processing and use of whole blood collected by procedures that closely follow those for standard allogeneic blood collection and stored for up to 35 days prior to autologous transfusion. Red cell and platelet components collected by apheresis are referred to briefly. Part 1: UK Legislation and Relevant European Directives Part 2: Literature review and current clinical practice Part 3: Recommendations based on an analysis of the above The UK Blood Safety Regulations 2005, which came into effect on November 8th 2005, transpose the European Commission Directive 2004/33/EC into UK law. This Directive in turn implements European Commission Directive 2002/98/EC. Two additional technical Directives were adopted by the European Commission on 30 September 2005 and according to the Medicines and Healthcare Regulatory Authority (MHRA), following public consultation will be transposed into UK legislation. These are: European Commission Directive 2005/61/EC regarding traceability requirements and notification of serious adverse reactions and events; European Commission Directive 2005/62/EC regarding community standards and specifications relating to a quality system for blood establishments. The Regulations and the Directives describe the legal requirements for collecting, processing, testing, transporting and storing blood components. They legislate principally for allogeneic transfusion, but there are several references to ‘autologous donation’ and ‘autologous transfusion’. Although they do not mention the terms ‘pre-operative’, ‘PAD’ or ‘PABD’, the context in which they are used clearly signifies that PAD is to be included. Although in general they require the same standards for allogeneic and autologous blood, they therefore do include additional ways of collecting and using autologous blood. The Regulations apply to blood establishments and to hospital blood banks. From 8th November 2005, UK hospital blood banks are required to submit an application for authorization to become a blood establishment if they collect or intend to collect autologous blood and blood components. In these Regulations Autologous transfusion means a transfusion in which the donor and the recipient are the same person and in which predeposited blood or blood components are used. Autologous donation means blood and blood components collected from an individual and intended solely for subsequent autologous transfusion to that same individual. In summary, the Regulations and Directives indicate that where blood and blood components are collected and tested for the sole purpose and exclusive use in autologous transfusion and are clearly identified as such, the requirements to be complied with shall be in accordance with those for allogeneic blood donation described European Commission Directive 2004/33/EC, which include testing for hepatitis B (HBs-Ag) hepatitis C (anti-HCV) HIV 1/2 (anti-HIV 1/2). Furthermore, autologous donations ‘shall be’ clearly identified and kept separate from allogeneic donations. With reference to information to be provided to donors, the Regulations require the reasons for requiring an examination and health and medical history, and the testing of donations, and the significance of ‘informed consent’ the possibility of deferral and the reasons why the donation would not in the of a health risk to the individual as donor or recipient of the autologous blood or blood components information on the of the procedures in the allogeneic or in the autologous donation process and for autologous donations, the possibility that the autologous blood and blood components may not for the intended transfusion requirements information as to why autologous blood and blood components will be and not to other patients The requirements set out in the Regulations and Directives include the be specifically as The possibility of deferral and reasons why the donation would not in the of a health risk to the individual as donor or as recipient of the autologous blood or blood The possibility that the autologous blood and blood components may not for the intended transfusion why autologous blood and blood components will be and not to other The reasons for requiring an examination and health and medical history, and the testing of donations, and the significance of The following deferral for autologous donation are in the cardiac disease on clinical setting of blood blood testing requirements are – above more than these and can from this legislation. Autologous blood donations should be in the same as allogeneic blood donation. when in the autologous blood is usually collected and in the same as allogeneic whole blood. may not be for PAD, but processing of PAD whole blood in the UK will include and blood components collected by apheresis – for autologous or allogeneic use – are to the same may be that autologous blood is to be blood will on storage and may transfusion reactions even in the autologous et al. patients that of PAD blood by is there are more of and of the reasons are not from the same were or However, as the are patients than donors, blood may be more to European Commission Directive 2005/61/EC to be transposed to UK in the requirements for traceability and notification of serious adverse reactions and and that Blood and Hospital for not than 30 the pertaining to traceability of blood, from collection from the donor to the ultimate of all components from that donation being to the required are in of the The Directive also the of serious adverse and serious adverse reactions to the in the in standard as in of the of PAD use is also covered by the Regulations and European Commission Directive 2005/62/EC to be transposed to UK in out all the standards and specifications for quality systems for blood establishments those hospital to to This Directive that all be stored from allogeneic donations. not to the donor be and the allogeneic blood all medical the use of PAD is and The of PAD in the medical of may be by the quality of the for standard allogeneic blood transfusion in that this the of allogeneic blood the and general standards of clinical to these into Although the Guidelines described are to the in the UK in of the from and include from Although PAD has been advocated for and such published was in the production of previous BCSH Guidelines more recent have been quality have been published and from the so the and benefit of PAD are described by Hardy In the published by et al. of the patients for surgery and who a Hb of g L−1 or more who the 42 were autologous and were The Hb concentrations at hospital and 6 weeks were not the Hb g and Hb in the g were in the autologous than in the and g L−1 in required an allogeneic transfusion. of the 42 an autologous transfusion. of the autologous were a of autologous there was an additional of for each in the donor et al. that autologous donation provided no benefit for patients without surgery. this a of of a using the series of from on the use of erythropoietin to boost haemopoiesis in adults and receiving surgery et will be The blood guidelines for is and but refers to no work published after They recommend that the for allogeneic blood should be with the and that patients healthy to elective surgery and with no medical to donation or storage of blood are healthy to PAD. Hb than 110 g L−1 is They recommend that PAD should only be considered when the of transfusion is more than elective surgery can be at several weeks in the is for which blood is usually for PAD with who are not or with where allogeneic blood may be in to for those with an a the may apply when medical heart disease disease They that PAD can be for the volume collected should be for – as they a blood loss to be of the estimated blood They no for PAD in but PAD in of should be as the for transfusion can be being an for the of by in estimated of were autologous, PAD, but there is and are The of has several the efficacy and of used to blood including PAD et et They the and relating to the use of alternatives to transfusion and that PAD, and cell salvage are with only in terms of the for allogeneic blood. Although PAD to allogeneic blood transfusion, it is with an in transfusion. are to transfusion in for a of surgical of procedures will not the of a These include a review on transfusion in elective surgery by the Guideline and the by et al. The guidelines that PAD should be only when it is to and which they a of PAD can be used to reduce allogeneic blood it the of transfusion which they an of PAD can be used in with which they a of PAD should be to men with Hb of g L−1 and to women with Hb of g L−1 which they a of PAD is not for patients Hb is g L−1 or more and are or surgery which they an of The guidelines also the of PAD with erythropoietin and that recommendations are based on three In patients surgery, they recommend that erythropoietin can be used in with autologous blood collection to reduce allogeneic transfusion, to which they a of This is also by the In patients surgery, they that erythropoietin can be used to cell donations an Hb on the of surgery. et al. that PAD the risk of receiving an allogeneic blood transfusion by interval The in risk of allogeneic transfusion was In the that the risk of receiving blood transfusion is by autologous blood donation risk were and was not described in of the They that the of PAD a in the for allogeneic blood, the quality of the was and the transfusion were and in those into the PAD This the benefit of PAD. In the of using clinical it is not to the of PAD the et al. a European in elective surgery, where the was low as of the PAD blood was used. to this to general in health European and recommend that PAD be and out that according to the of for Blood and of the of Blood which is by the PAD should be and to all This that to be indicate that the risk of by become so that become the of by blood could public health is three the of in three of the UK who blood by who developed Agency this risk has now become more but as of the UK before has been to this is not a current for the majority of UK This have to be as in the UK after to require surgery – the are to include requiring surgery during the that PAD is a form of They the reasons for the in PAD use from its in the and that are estimated quality of of than for all types of surgery, for et al. that of the PAD requiring a than that for allogeneic healthy donors, that use of PAD in with other blood conservation in referral of all patients for PAD is and should be They do not the for which they PAD to be They also comment that risk of be or if blood to with for blood, the may et al. the above and the same that in are to patients PAD, it is not without and is a and patients are on the of surgery, transfusion – autologous or even allogeneic – more they also it is to the of and that to may no be based on the of the blood but on evidence that blood conservation is and of for individual In an to the and of the Blood a of autologous collection provided from the at covering the from to They that and surgery have blood requirements and may benefit form PAD. PAD is use in other elective surgical However, the were not using cell salvage at that time it is now similar in the appropriate use of PAD and the recommendations in Blood for the Blood and the Blood which recommended that PAD be to patients with blood and for whom it would be to allogeneic blood PAD be to patients health be at risk using allogeneic blood blood transfusion, including PAD, at the time of allogeneic for cell be no In the of using clinical it is not to of PAD should be that et al. an adverse to autologous which was than that in allogeneic The Guidelines of 1993 recommend that iron should be to all patients who predeposit before the first donation and continued recent on the efficacy of oral iron particularly in the of prior et al. from that oral iron the of autologous blood collection in patients with Hb above g et al. from that oral iron therapy in patients a of three autologous is not Although et al. from that oral iron the production of Hb in autologous blood more than additional iron did not to a in a for elective surgery to transfusion is to be iron clinical practice for the of the and so that the is iron prior to surgery et Guideline Although the Guidelines of 1993 that the for erythropoietin in PAD are and do not recommend several before and have this and particularly a of erythropoietin and iron or In the et al. describe for to boost haemopoiesis and reduce the for allogeneic for days days or three and on of surgery. are of benefit and in and In with PAD, et al. haemopoiesis in healthy also comment that erythropoietin to allogeneic transfusion in and cardiac surgery but recommended to the of erythropoietin to the optimal of erythropoietin and to its efficacy and with other of transfusion. However, et al. that the in cell volume could be with erythropoietin therapy according to the volume where erythropoietin of The erythropoietin was on a to an in a of erythropoietin are in to the in the of September this would et al. in a of healthy men erythropoietin for weeks – a of that it was in healthy men to donate blood mL) a week for weeks also et that the use of iron with erythropoietin to be to and to reduce the of Furthermore, they that oral iron may be to patients who it as there are no and a efficacy be The review that the optimal of erythropoietin to a PAD is not it is that is in these However, these are The indicate that for patients the recommended by et al. would for the of and for the of three has always been by oral or iron therapy, but an optimal iron has not been et al. in a of adults and surgery advocated PAD with erythropoietin but of in and in et al. children, with of 6 surgery for or but could not of – and The participants were Two recent et al. and et al. a of PAD and erythropoietin in and surgery. et al. receiving PAD without erythropoietin – – to have Hb required allogeneic blood more often than those PAD was by The were to donate more blood and more were to the PAD of autologous were by of more so the The of in those who were on to the and with each and on the of surgery for the In a of patients who were et al. (1991) that PAD from the is and and the in elective of They also that iron therapy three with or without three the of Hb compared with those who no such Although the were for a from with is that autologous blood donation is in patients is by and by et al. as PAD can be with of up to of autologous blood In an as Health et al. describe of PAD with allogeneic blood et et that PAD was not et al. that PAD in patients a health at some of the was on of hepatitis but so on They also that as blood the of PAD and that even a of risk with PAD in a cardiac all of PAD. et al. also that the of PAD use was and may not the and that PAD was not more cost-effective than a In the other three of the that PAD was These were by et al. (1994), who compared with use of allogeneic blood a of and transfusion et al. based on hospital in which the of autologous blood was whereas hospital by allogeneic and that patients allogeneic blood on of autologous hospital to which of They also that in which they such patients were more as a of receiving allogeneic also to The of the three was that of et al. in a that even if there were a in the risk of following allogeneic transfusion, PAD would in at a that favourably with health has to be in that these were undertaken in several in circumstances that may not in the UK at or in the The of erythropoietin therapy, even when by iron therapy, to the of PAD. From the et on PAD is by the significant to be of the in the a for to the recommendations described in the UK recommendations described in Blood the with this as by the current in of allogeneic to in in to an estimated for the that all blood are volunteers the current of of by transfusion of allogeneic blood components from UK in the of the UK which are in 500 for in for HIV in 30 for in surgical resulting in blood requirements use of autologous transfusion which BCSH guidelines are being for alternatives to allogeneic blood transfusion The use of PAD is not recommended unless the clinical circumstances are exceptional. circumstances may include blood where allogeneic to with at serious risk if blood transfusion is to be to elective surgery who to consent to allogeneic transfusion but who would consent to PAD PAD of whole blood is the following are required but do not of it if they can be considered for the be for elective surgery, where blood transfusion is expected to be The and days be time to optimal collection of the blood be prior to surgery but should not the time for storing the collected blood For this is in practice at weeks time should be from the and time of the ultimate PAD collection prior to surgery for the to a and The of the of the of Blood recommend a interval of should be by a to be to the loss of the volume of blood at each this should be no more than of estimated blood volume should be provided with information the for PAD and the reasons such by the the PAD should be considered for with erythropoietin should with the following Hb before on PAD g L−1 g L−1 For each individual there should be a for PAD to allogeneic blood as PAD is not for patients the above the clinical for collecting and using PAD are for the majority of patients elective surgery of a to require transfusion to surgical and blood allogeneic blood is the PAD is not recommended for than of technical in of and it can be to means of use of allogeneic blood should be such as cell who the for PAD but who are for of for collecting and processing the donations and also for and other For these the not recommend that PAD be to such patients unless they also into of the the of its to PAD be as The therefore not recommend that erythropoietin be used unless the clinical circumstances are exceptional. Although iron therapy prior to PAD has effect on subsequent transfusion in who are iron there are of iron therapy during PAD on a there is no clinical evidence on which to such the not recommend iron to PAD and that PAD be to who are iron and receiving iron therapy they have been and iron the collection of allogeneic cell component donations by apheresis more autologous cell component collection by apheresis may also be for cell component collection by may also be for volume and of donation and therefore be have a blood Hb than Hb for standard allogeneic donation g and have iron However, there are no of such systems applying to PAD. The not recommend that PAD be by apheresis and unless become with those for standard donation collection and processing, and even only the circumstances pertaining to PAD by standard collection Although the advice and information in these guidelines are to be and at the time of to the the for the legal for the of these