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Guidelines for pre‐transfusion compatibility procedures in blood transfusion laboratories

2012; Wiley; Volume: 23; Issue: 1 Linguagem: Inglês

10.1111/j.1365-3148.2012.01199.x

1365-3148

Clare Milkins, J. Berryman, Clark V. Cantwell, C. Elliott, R. Haggas, J. Jones, M Rowley, Mark Williams, Nay Win,

Blood donation and transfusion practices

Contents The effective development and maintenance of satisfactory standards in pre-transfusion testing requires a structured approach in the adoption of a quality management system. Technical errors, clerical errors, the use of non-validated techniques or equipment and non-compliance with established procedures may result in missed incompatibilities and immediate or delayed haemolytic transfusion reactions (SHOT, 1996–2010; Stainsby et al., 2006). The purpose of these guidelines, which replace those published in 2004 (Chapman et al., 2004), is to define the laboratory processes and procedures that should be adopted to undertake pre-transfusion testing. The guideline group was selected to be representative of UK-based medical, scientific and technical experts. The writing group produced the draft guideline which was subsequently revised by consensus by members of the Transfusion Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the BCSH (British Committee for Standards in Haematology) and the Transfusion Laboratory Managers Working Group of the National Blood Transfusion Committee and its equivalent in the other three countries, and comments incorporated where appropriate. These guidelines are formulated from expert opinion and based on the requirements of the Blood Safety and Quality Regulations (BSQR, 2005), and the recommendations of Clinical Pathology Accreditation (CPA, 2010), Guidelines for Blood Transfusion Services in the UK (UK Blood Transfusion Services, 2012), the UK Transfusion Laboratory Collaborative (Chaffe et al., 2009), and data from UK NEQAS (BTLP) (Knowles et al., 2002; UK NEQAS ANNUAL REPORTS) and the Serious Hazards of Transfusion (SHOT) haemovigilance scheme annual reports (SHOT, 1996–2010). Where evidence exists to support new and potentially contentious recommendations, this is referenced in the text. The quality section includes all of the quality recommendations from the whole guideline, so those using this guideline should refer back to the quality section for advice relating to individual sections. All aspects of testing relating to emergency situations have been put into a separate section – Section 8. Other sections now relate solely to routine testing. Efforts have been made to avoid duplication and overlap with other guidelines. This guidance is complementary to the BCSH guidelines that cover transfusion of paediatric patients, antenatal serology, information technology (IT) systems, administration of blood components and validation in the transfusion laboratory (BCSH, 2004, 2006a,2006b, 2009, 2010a), and these should be available for reference. The referenced versions of these guidelines were current at the time of publication of this document but it is recognised that they may be updated during the lifetime of this guideline, and reference should always be made to the current version. Where expansion on the decision making on the recommendations is required, this is covered in a series of appendices. Recommendations are based on overriding principles, but it is recognised that a safe outcome may be achieved using a different approach, whilst still complying with minimum standards. In these circumstances, a fully documented risk assessment is required. Exceptions to policy relating to individual patients are now covered by a statement relating to concessionary release and an example is given in Appendix APPENDIX 9. There is an additional section relating to what happens after components have been issued, and the serological investigation of a suspected transfusion reaction. There are new flow charts for anomalous D typing and selection of blood in this circumstance, and for anomalous ABO typing (Appendix APPENDIX 3). There are worked examples of antibody identification in Appendix APPENDIX 4. KEY RECOMMENDATION: The laboratory must identify all critical control points in pre-transfusion testing and build in security at these points. KEY RECOMMENDATION: Laboratories must have contingency plans for actions to be taken when normal systems are not available. KEY RECOMMENDATION: The laboratory should have a policy with respect to the manual editing and authorisation of test results. Errors in patient identification and sample labelling may lead to ABO-incompatible transfusions. Evidence for this is well documented in the annual reports of the SHOT steering group (SHOT, 1996–2010) and by others (Stainsby et al., 2006; Sazama, 1990). KEY RECOMMENDATION: Serological studies should be performed using blood collected no more than 3 days in advance of the actual transfusion when the patient has been transfused or pregnant within the preceding 3 months. Whole-blood samples will deteriorate over a period of time. Problems associated with storage include red cell lysis, bacterial contamination, decrease in potency of red cell antibodies, particularly immunoglobulin M (IgM) antibodies and the loss of complement activity in serum samples. Table 1 gives suggestions for working limits (if times are extended this must be supported by local risk assessment prior to implementation). KEY RECOMMENDATION: A pre-transfusion sample should be retained for at least 3 days post-transfusion, to ensure that repeat ABO grouping of the pre-transfusion sample can be performed in the event of an acute transfusion reaction. For more discussion on the recommendations regarding timing of sample collection, storage of samples and use of physical separators, see Appendix APPENDIX 2. KEY RECOMMENDATION: ABO grouping is the single most important serological test performed on pre-transfusion samples and the sensitivity and security of testing systems must not be compromised. KEY RECOMMENDATION: Fully automated systems should be used where possible to reduce the risks of interpretation and transcription errors. KEY RECOMMENDATION: Any abbreviation of the ABO group must be fully risk assessed. KEY RECOMMENDATION AND CRITICAL POINT: The patient demographics on the sample should be checked against the computer record prior to validation of results (preferably prior to testing), to ensure that they match and no errors have been made during data entry onto the LIMS. KEY RECOMMENDATION: If the patient is known to have formed a red cell alloantibody, each new sample should be fully tested to identify or exclude the presence of further alloantibodies. CRITICAL POINT: A check should be made to ensure that the panel results do not conflict with the antibody screening results which may reflect manual tests being performed on the wrong sample. KEY RECOMMENDATION: When one antibody specificity has been identified, it is essential that the presence or absence of additional clinically significant antibodies is established. KEY RECOMMENDATION: Unless secure electronic patient identification systems are in place, a second sample should be requested for confirmation of the ABO group of a first time patient prior to transfusion, where this does not impede the delivery of urgent red cells or other components. KEY RECOMMENDATION: The indirect antiglobulin test (IAT) crossmatch is the default technique which should be used in the absence of functioning, validated IT or when electronic issue is contra-indicated. KEY RECOMMENDATION: An IAT crossmatch must be used if the patient's plasma contains, or has been known to contain, red cell alloantibodies of likely clinical significance. KEY RECOMMENDATION: The overall process for determining eligibility for EI must be controlled by the LIMS and not rely on manual intervention or decision making. KEY RECOMMENDATION: Laboratories should have written protocols in place which define the responsibilities of all staff in dealing with urgent requests. KEY RECOMMENDATION: For genuinely unknown patients, the minimum identifiers are gender and a unique number. KEY RECOMMENDATION: Following an emergency rapid group, a second test to detect ABO incompatibility should be undertaken prior to release of group specific red cells. KEY RECOMMENDATION: If the DAT is positive, an eluate made from the patient's red cells should be prepared and tested for the presence of specific alloantibodies. It is not unusual for the causative antibody to be present in an eluate but absent in the plasma. None of the authors have declared a conflict of interest. While the advice and information in these guidelines is believed to be true and accurate at the time of going to press, neither the authors, the British Society for Haematology, nor the publishers accept any legal responsibility for the content of these guidelines. Table A1 shows examples of critical control points in the compatibility process and risk reduction strategies. The list is not exhaustive but gives examples of some critical control points. Mapping the full compatibility process in each laboratory will aid in identifying these points. • Checking sample barcode against LIMS system after booking in • Automated testing – possible interface / testing errors • Validation of testing system and interface • Special requirements missed • Labelling wrong donations – mix up between patients • Warning in LIMS system if wrong component is selected • Highlighting requirements on request form • Performing only one crossmatch / electronic issue labelling at a time There is a dearth of published data regarding when red cell alloantibodies form and are first detectable following a stimulating event (be it a primary or secondary response). Of the papers available for review it is clear that only a very small percentage of antibodies which are below detectable level pre-transfusion become detectable in the first 72 h, estimated at 2.3% (Schonewille et al., 2006), and supported by SHOT data (SHOT, 1996–2010). Mollison reports that red cell destruction does not begin before the 4th day post-transfusion (Klein & Anstee, 2005b). Following this time, most developing antibodies will manifest themselves within the next 30 days (there are occasional stragglers), and by 3 months post-transfusion very few antibodies will develop. SHOT data shows that the majority of delayed haemolytic transfusion reactions are noted 3–14 days post-transfusion. It was on this basis that the previous guidelines recommended a 24-h lifespan for a sample when the patient had been transfused within the previous 3–14 days. A survey of UK laboratory practice, undertaken by the writing group (through UK NEQAS), revealed that a minority of laboratories comply with this guideline. However, when taking into account the combination of the age of the sample and the length of time that the blood sits in the issue fridge, approximately 80% transfuse within 72 h of a new sample being taken (Milkins et al., 2010). The vast majority of all UK laboratories report through SHOT, and there do not appear to be significant numbers of additional delayed haemolytic transfusion reactions being reported as a result of this. It would seem that empirical evidence would point to the previous 24 h recommendation being unnecessarily tight. The writing group also noted recommendations from other countries which have longer times, e.g. the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) in the USA require an antibody test within 3 days prior to red cell transfusion, while the Canadian Society for Transfusion Medicine recommends that a specimen be collected within 96 h prior to transfusion. With a significant number of laboratories unable to achieve the existing guideline combined with the empirical evidence above, the writing group felt that a change that represented a balance of safety with achievability was required. With this in mind, the group took the decision to change the model to the length of time of red cell units issued against a particular sample are available. With regard to the published data on alloantibody formation, transfusion reaction reporting, and the survey, it was felt that a blanket 3-day period up to 3 months post-transfusion, offered the best balance of safety and achievability. A laboratory could interpret this as a 24-h sample life + 48-h reservation period, or as a 48-h sample life with 24-h dereservation period, or some other combination as they felt best met local conditions. It is recognised by the group that the scientific evidence for such a decision is limited and that this should be considered as a baseline only. Those laboratories wishing to have stricter time frames more in line with the existing guidance could do so; those wishing to use more lenient time frames would have to support their decision through a local risk assessment. It may be that some feel able to accept these new time frames for patients with no previous antibody history but may be more reluctant for patients with existing antibody histories (there is some evidence that the presence of an antibody is likely to predict further formation of antibodies as it indicates ‘good responders’) or those in high risk groups, e.g. those with sickle cell disease. One size fits all does have the benefit of being understandable by all staff (clinical and laboratory). There is almost no published data on storage times, storage temperature or length of time a sample remains suitable for testing, so the writing group has decided not to significantly alter the existing recommendations until new data become available. Because of a number of unpublished communications within and outside the writing group where patients not seen for some time appear for treatment and have, unknown to laboratory, been transfused elsewhere, it was felt that a period of no more than 3 months should be recommended as a maximum for samples to remain suitable for issue of red cells. This should allow laboratories to cater for electronic issue of blood on preoperative assessed patients' samples while limiting the possibility of unexpected transfusion at an alternative site. The availability of pre-transfusion samples to investigate transfusion reactions varies considerably from site to site. The group felt that having such a sample to test as part of a transfusion reaction investigation represented best practice, allowing determination of whether the antibody was previously undetectable or had been missed as a result of system frailty. It is usual in Good Manufacturing Practice (GMP) industries to ensure sample availability for testing in the event of subsequent product problems. The group particularly felt that having a pre-transfusion sample to test for ABO status in the event of an acute transfusion reaction was highly desirable and so recommended that systems are put in place to ensure that a sample for testing was available for a minimum of 3 days post-transfusion. The writing group suggests that being able to retain a plasma/serum sample for up to 14 days post-transfusion would be desirable for delayed transfusion reaction testing for similar reasons to those of an acute transfusion reaction. This would require separation and freezing of the plasma from the red cells. Laboratories are, for good reasons, not comfortable with separation and the risk associated with the labelling, into separate plasma pots. However, if physical separators (these are devices that are commercially available that can be introduced post routine testing into the primary sample, inserting a physical barrier between the red cells and plasma) are used this then negates the need for plasma separation while retaining plasma for testing and the original sample tube for inspection of patient ID as necessary. The writing group noted that other countries also required retention of samples post-transfusion (e.g. JCAHO in USA requires samples to be retained for at least 7 days following a transfusion and 10 days following a crossmatch). The writing group recognises that implementation of these recommendations and suggestions may entail changes in laboratory procedures and investment in new equipment. However, it feels that the benefits of ensuring a full audit trail of transfusion reaction events to patient, individual laboratories and transfusion medicine as a whole (by allowing collection of data in an area of non-existent data) are substantial enough to support their inclusion. Figure A1 shows a flowchart for the resolution of ABO grouping anomalies. In the following examples, the shaded cells show specificities which can be excluded with one or more examples of homozygous expression (or in the case of Kell, Kk) on ID panel or screening panel. In addition, antibodies to antigens of unlikely clinical significance or low incidence are also shaded where appropriate, to demonstrate their exclusion. However, it is not necessary to routinely exclude such specificities, unless there are positive reactions unaccounted for once all antibodies of likely clinical significance have been identified. Where reference is made to exclusion based on negative results using an enzyme panel, this assumes that a validated two-stage test has been used, i.e. using enzyme pre-treated cells. Figure A2 shows the results of the identification panels for Example 1. Interpretation: Shaded cells show that all antibodies of likely clinical significance can be excluded on the identification panel except anti-s, anti-c and anti-E. Anti-s can be excluded by considering the negative result with the c-, ss screen cell 1. Specificities which still cannot be excluded are: anti-c, -E. Positive IAT with all c+ cells (>2 available) and negative with all c- negative cells (>2 available including screen cell 1). Identification: anti-c Unable to exclude anti-E, however, if CCDee cells are selected for transfusion it is unnecessary to do so. Use of CCDEe cells may be required for antenatal samples. Additional work: Rh phenotype Figure A3 shows the results of the identification panels for Example 2. Interpretation: Rh specificities can be excluded using negative enzyme panel results. Shaded cells show that all other specificities can be excluded except anti-M. Positive IAT with all M+ cells (>2 available) and negative with all M- negative cells Identification: anti-M Additional work: M phenotype Figure A4 shows the results of the identification panels for Example 3. Interpretation: Rh specificities other than anti-D and -C can be excluded using negative enzyme panel results. Anti-M, -S, are excluded using screening cell 3. Shaded cells show that all other specificities of likely clinical significance can be excluded except anti-D, -C, -Jkb Anti-D identified using enzyme panel results: all D+ cells (> 2 available) positive and all D- cells (>2 available) negative except r′r suggesting additional anti-C. Positive with all Jk(b+) cells (>2 available) and negative with all Jk(b-) negative cells (>2 available, which are also D- and C-). Anti-Lea cannot be excluded but the reactions do not interfere with the identification criteria for the above antibodies. Identification: anti-D+ Jkb+ probable anti-C Additional work: Jkb phenotype; test plasma vs additional D-, C+ cell to confirm anti-C. Figure A5 shows the results of the identification panels for Example 4. Interpretation: IAT positive with all cells Enzyme positive with all cells Identification: Unable to identify Exclusion: Unable to exclude Additional work: Auto IAT result negative, indicates one or more alloantibody, rather than pan-reacting/autoantibody Patient phenotype: C+c-D+E-e+, M-N+, S-s+, P1+, K-, Le(a-b+), Fy(a+b-), Jk(a+b-). Patient can therefore produce alloanti-c, -E, -M, -S, -K, -Fyb, -Jkb Figure A6 shows the results of the additional panel cells used to Identify/exclude additional specificities: Alloantibodies excluded either on patient phenotype, or cells 15 (anti-M, -S) and 16 (anti-Fyb), except anti-c, -E, -K, -Jkb. Identification Anti-c+(+/− anti-E), -K, +Jkb Table A2 gives examples of additional techniques than can be useful for antibody identification. Table A3 shows the likely clinical significance of red cell alloantibodies, and recommendations for the selection of blood for patients with their presence. This recommendation is based on the evidence from the BEST studies as referenced in 7.2, and on data from the IBCT and the Near Miss chapters in recent SHOT reports (SHOT, 1996–2010) – 386 cases of ‘wrong blood in tube’ (WBIT) were reported as near misses in 2010. Whenever possible a second sample should be obtained. The urgency of the situation should always be considered, as delays in provision of blood could compromise patient outcome. When, in an urgent situation only, it is not possible to obtain a second sample, group-specific red cells should not be issued without a second ABO check for ABO compatibility. The options for this are a second group on the same sample, preferably undertaken using a different method/reagents from a fresh sampling and/or a serological crossmatch. In these circumstances a local risk assessment, including identification of clinical areas where WBIT errors have previously originated, systems currently in place for training of clinical and laboratory staff, and electronic systems for patient identification and sample collection, should be undertaken. Depending on the outcome of the local risk assessment consideration should be given to whether it is safe to issue group-specific red cells or whether group O units should be transfused in an emergency until a second sample has been processed. It should be noted that this could make it difficult to obtain a clear ABO/D group from subsequent samples as mixed field reactions may be obtained. Where the patient groups as O on the first sample, there is an argument for not requiring a second sample prior to transfusion, as the patient will safely receive group O red cells. There are two issues to consider and risk assess before implementing such a strategy: the first is whether this decision can be controlled by the LIMS (a requirement for electronic issue); the second is the potential for transfusion of large volumes of incompatible, potentially high-titre, group O plasma, and consideration should be given to selection of group AB fresh frozen plasma (FFP) and group A platelets in these circumstances, until the ABO group has been confirmed on a second sample. Concerns have been expressed that the two samples may be taken at the same time, but one ‘saved’ to send to the transfusion laboratory at a later time. It is important to have a policy and process in place to assure that the two samples have been taken independently of one another, and those taking samples for transfusion, need to understand the reasons for requesting a second sample and the risk of WBIT. As discussed in Section 7, the LIMS needs to be in full control of the algorithms associated with selection of patients for electronic issue, and one of the main exclusions are patients with clinically significant red cell antibodies, whether in the current sample or historically. This makes it difficult to safely issue blood by EI if the antibody screen is positive. MHRA recommends that there are no manual workarounds for selection of patients (MHRA, 2010). It is recognised that the scenario of a positive screen due to prophylactic anti-D is likely to be contentious: As described above, the main difficulty is managing the algorithm for patient acceptance for EI. Some laboratories use a set of rr screening cells in these circumstances, which would result in a negative antibody screen, allowing the sample to meet the criteria for EI. However, this in itself requires a human decision process which is not controlled by the LIMS, and is reliant on the correct clinical information being provided. Patients with immune anti-D could be missed. It should also be remembered that there is no reliable way of distinguishing serologically between immune and prophylactic anti-D, and mistakes have been made both ways as described in various SHOT reports (SHOT, 1996–2010). If electronic issue is undertaken in these circumstances there should a full risk assessment. It should be recognised that these patients are a small minority of those requiring transfusion support and for these few patients it should not be onerous to perform a serological crossmatch. However, in a major obstetric haemorrhage, concessionary release could be used to rapidly issue D negative red cells without a serological crossmatch. Concessionary release of blood components or blood products, or acting contrary to an SOP, is sometimes the necessary and appropriate course of action in the best interest of patients. To act contrary to an SOP requires prior authorisation, or justifiable authorisation as soon after as is practicable, preferably by a haematologist or other suitably competent person who should discuss the clinical consequences with the clinicians in charge of the patient. An example is shown in Fig. A7.