Transfusion Medicine
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LETTER TO THE EDITOR
HPA-1a(−), 5b(−) platelets for use in neonatal alloimmune thrombocytopenia – from ‘Cinderella’ product to standard component Dear Sir, Antibodies against human platelet antigen (HPA)-1a and HPA-5b together account for ∼95% of serologically confirmed cases of neonatal alloimmune thrombocytopenia (NAIT) in the UK (Ghevaert et al., 2007). The transfusion of HPA1a(−), 5b(−) platelets to neonates in suspected cases of NAIT is therefore the logical clinical intervention to correct the platelet count and immediately reduce the risk of intracranial haemorrhage. The first intentional use, as opposed to serendipitous use (Murphy et al., 2001), of neonatal HPA1a(−) platelets in a case of suspected NAIT in the UK occurred in the early 1980s (Prof. M. Murphy, NHS Blood & Transplant (NHSBT), Oxford – personal communication). ‘The Guidelines for the Blood Transfusion Services in the UK (2013)’ advise that the affected infant in suspected NAIT cases should be transfused with HPA selected platelets suitable for neonatal use. The platelet count should be maintained above 30 × 109 L−1 , or greater if there is evidence of bleeding (UK Blood Transfusion and Tissue Transplantation Service Handbook, 2007). Intravenous IgG (IvIgG) used either alone or in conjunction with platelet transfusions has also been used in this setting but, when IvIgG is used in isolation, there is often an unacceptable delay of between 24 and 72 h before the platelet count increases (Murphy and Bussel, 2006). Since 2000, the English Blood Transfusion Service has adopted a policy of providing HPA1a(−), 5b(−) neonatal platelets as an ‘off-the-shelf’ product in five designated stock locations – currently, NHSBT centres in Colindale, Filton, Manchester, Sheffield and Tooting. The ready availability of HPA-1a(−), 5b(−) platelets means that optimal platelet provision can be given to neonates with suspected NAIT within a few hours. This avoids any delay in waiting for laboratory results, although these investigations should be initiated immediately to confirm the diagnosis and prevent unnecessary use of HPA-1a(−), 5b(−) platelets in cases where there is no laboratory evidence for NAIT. HPA-1a(−), 5b(−) platelets are obtained from accredited donors that have been shown to be negative for anticytomegalovirus antibodies, high titre anti-A and anti-B, other red cell antibodies, HPA-specific antibodies, HLA antibodies and, for female donors, granulocyte specific antibodies. This
Correspondence: Dr Geoff F. Lucas, PhD, FRCPath, Department of Histocompatibility and Immunogenetics, NHS Blood and Transplant, North Bristol Park, North Way, Filton, Bristol, BS34 7QH, UK. Tel.: +(44) 117 921 7536; fax: +(44) 117 912 5730; e-mail: [email protected]
© 2014 The Authors Transfusion Medicine © 2014 British Blood Transfusion Society
specification also enables these donors to donate platelets for intrauterine transfusion (IUT). These donors are typed for HPA1, -2, -3, -4, -5, -6, -9 and -15, which means that these donations also have the potential to support NAIT cases due to other antibody specificities, e.g. anti-HPA-3a. The accredited donors are also occasionally used to supply platelets for IUT in cases where there is foetal thrombocytopenia due to other causes, e.g. parvovirus infection. Until recently, platelet donations from accredited HPA1a(−), 5b(−) donors were identified with labels that were attached to luggage tags by staff in the donor collection centre. This meant that the 14 character donation number had to be manually transcribed up to 12 times – as would occur when a donor donated three adult doses of platelets because each adult dose had the potential to be split into four neonatal units. Manual labelling was labour intensive and always at potential risk of human error. This risk was partly mitigated by restricting the collection of HPA-1a(−), 5b(−) platelets to eight donor centres where there were a significant number of accredited donors and staff could become familiar with the labelling process. However, this prevented labelling of donations at sites where there were only a few accredited donors. On rare occasions, it has not been possible to supply HPA1a(−), 5b(−) platelets when required either because stock was held in a different holding location and could not be seen literally or electronically, because of a lack of donor availability or because of high demand (or due to a combination of these factors). Consequently, maintaining neonatal platelet stock levels often required intensive management, including asking donors to reschedule appointments at short notice and moving donations between centres to maintain minimum stock levels. In a few cases, it has been necessary to provide neonates with random platelets rather than HPA-1a(−), 5b(−) platelets. This is acceptable practice in severely thrombocytopenic infants at risk of bleeding prior to the arrival of HPA-1a(−), 5b(−) platelets and has been shown to provide satisfactory increments in some cases (Kiefel et al., 2006). However, random platelets can often be ineffective resulting in reduced increments and with a shorter halflife compared with HPA compatible platelets (Allen et al., 2007). In an attempt to address the problem of product availability, two major information technology (IT) based initiatives have been introduced. The first of these was to assign a blood characteristic (accredited HPA donor – ACHPA) to all active accredited HPA-1a(−), 5b(−) platelet donors so that the associated donations could be searched using the national blood component and donor management IT system (PULSE) and located anywhere in the country, irrespective of stock location. The
doi: 10.1111/tme.12108
128 Letter to the Editor • A total of 97 of 105 (92.4%) of donors made at least
• •
•
•
Fig. 1. Computer generated HPA-1a(−), 5b(−) label produced at validation. The label includes an eye-readable and barcode-readable donation number and the donor’s HPA genotype.
second initiative introduced computer controlled labelling so that a label is produced at product validation after all mandatory tests have been completed – in exactly the same way as for other blood components. The label produced identifies that the donation is HPA-1a(−), 5b(−) and provides the HPA genotype of the donor (HPA-1 to -5 and -15), see Fig. 1. The instruction to produce this label is centrally controlled by staff with responsibility for managing and monitoring donor accreditation. The introduction of computer controlled HPA-1a(−), 5b(−) labelling was introduced over a period of 10 months and five phases of work. Manual labelling was maintained as a ‘fail-safe’ procedure to ensure operational continuity. Phase 1 established that the labelling worked in practice and identified potential problems. Phase 2 introduced computer controlled labelling for donations collected from donor centres in Bristol, Oxford and Plymouth and was carefully monitored over a 10-week period to refine the new procedure. Phase 3 established that the labelling also worked in practice for platelet hyperconcentrate donations destined for IUT. Phase 4 introduced labelling for donations collected from donor centres in Lancaster, Liverpool and Manchester and later in the donor centres at Brentwood and Cambridge. In the fifth and final phase, the results of the project were reviewed and the manual labelling procedure was withdrawn in favour of the computer-based system. The key results of the project were as follows: • A total of 105 of 115 accredited donor records were
‘activated’ for computer labelling; the remaining 10 donors had been temporarily deferred.
REFERENCES Allen, D.A., Verjee, A., Rees, S., Murphy, M.F. & Roberts, R.J. (2007) Platelet transfusion in neonatal alloimmune thrombocytopenia. Blood, 109, 388–389.
Transfusion Medicine, 2014, 24, 127–129
one donation which was successfully computer labelled at validation. A total of 80 (76.2%) donors made two or more donations which were successfully computer labelled at validation. A total of 8 (7.6%) donor records were ‘activated’ but labels were not produced during the study period either because the donor did not attend after ‘activation’ or because the product was discarded prior to validation. At least three platelet hyperconcentrates were prepared using donations from accredited donors and labels were successfully produced. Donations from seven accredited donors who had moved to a different donor centre could be computer labelled thereby increasing the total number of accredited donors by 6% to 122.
These changes have increased the availability and awareness of HPA-1a(−), 5b(−) platelets because labelling is more secure and accredited donors can be recruited at additional donor collection sites. The donations are automatically labelled after product validation reducing manual intervention and increasing operational efficiency without the potential errors associated with manual transcription. Increased product availability combined with the ability to locate HPA-1a(−), 5b(−) platelets in different stock locations will result in improved clinical outcome for neonates with suspected NAIT.
ACKNOWLEDGMENTS GL planned and oversaw all the changes for this study and wrote the manuscript. NB made changes to and carefully reviewed the donor records and labelling and contributed to the manuscript. Many NHSBT staff contributed to the success of this work. We especially wish to thank: Helen Cerullo, Annmarie Endicott, Ann Green, Jeremy Kellington, Adrian Marsh, Edwin Massey, Nuru Mwandoro, Jessica Tovey, Stuart Penny, Julia Sault, Kelly Venus and David Winstone for their support.
CONFLICT OF INTEREST The authors have no competing interests. G. F. Lucas & N. Bendukidize Department of Histocompatibility and Immunogenetics, NHS Blood and Transplant, Filton, UK
Ghevaert, C., Campbell, K., Walton, J., Smith, G.A., Allen, D., Williamson, L.A., Ouwehand, W.H. & Ranasinghe, E. (2007) Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia. Transfusion, 47, 901–910.
‘Specifications for blood components’. In: Guidelines for the Blood Transfusion Services in the United Kingdom (Red Book) (8th edn). (2013) (ed. MaClennan S.), 7, Sections 29 & 30. The Stationery Office, Norwich.
© 2014 The Authors Transfusion Medicine © 2014 British Blood Transfusion Society
Letter to the Editor Kiefel, V., Bassler, D., Kroll, H. et al. (2006) Antigen – positive platelet transfusion in neonatal alloimmune thrombocytopenia (NAIT). Blood, 107, 3761–3763. Murphy, M.F. & Bussel, J.B. (2006) Advances in the management of alloimmune thrombocytopenia. British Journal of Haematology, 136, 366–378.
Murphy, M.F., Knechtli, C., Downie, C., Rogers, S.E. & Lucas, G.F. (2001) Serendipity and the use of random donor platelets in fetomaternal alloimmune thrombocytopenia (FMAIT). British Journal of Haematology, 113, 1076–1089. ‘Transfusion in antenatal obstetric and neonatal care’. In: UK Blood Transfusion and Tissue
© 2014 The Authors Transfusion Medicine © 2014 British Blood Transfusion Society
129
Transplantation Service Handbook (4th edn). (2007) (ed. MacLennan, D.B.L.) Section 6, p51–57. The Stationery Office, Norwich.
Transfusion Medicine, 2014, 24, 127–129
|
LETTER TO THE EDITOR
HPA-1a(−), 5b(−) platelets for use in neonatal alloimmune thrombocytopenia – from ‘Cinderella’ product to standard component Dear Sir, Antibodies against human platelet antigen (HPA)-1a and HPA-5b together account for ∼95% of serologically confirmed cases of neonatal alloimmune thrombocytopenia (NAIT) in the UK (Ghevaert et al., 2007). The transfusion of HPA1a(−), 5b(−) platelets to neonates in suspected cases of NAIT is therefore the logical clinical intervention to correct the platelet count and immediately reduce the risk of intracranial haemorrhage. The first intentional use, as opposed to serendipitous use (Murphy et al., 2001), of neonatal HPA1a(−) platelets in a case of suspected NAIT in the UK occurred in the early 1980s (Prof. M. Murphy, NHS Blood & Transplant (NHSBT), Oxford – personal communication). ‘The Guidelines for the Blood Transfusion Services in the UK (2013)’ advise that the affected infant in suspected NAIT cases should be transfused with HPA selected platelets suitable for neonatal use. The platelet count should be maintained above 30 × 109 L−1 , or greater if there is evidence of bleeding (UK Blood Transfusion and Tissue Transplantation Service Handbook, 2007). Intravenous IgG (IvIgG) used either alone or in conjunction with platelet transfusions has also been used in this setting but, when IvIgG is used in isolation, there is often an unacceptable delay of between 24 and 72 h before the platelet count increases (Murphy and Bussel, 2006). Since 2000, the English Blood Transfusion Service has adopted a policy of providing HPA1a(−), 5b(−) neonatal platelets as an ‘off-the-shelf’ product in five designated stock locations – currently, NHSBT centres in Colindale, Filton, Manchester, Sheffield and Tooting. The ready availability of HPA-1a(−), 5b(−) platelets means that optimal platelet provision can be given to neonates with suspected NAIT within a few hours. This avoids any delay in waiting for laboratory results, although these investigations should be initiated immediately to confirm the diagnosis and prevent unnecessary use of HPA-1a(−), 5b(−) platelets in cases where there is no laboratory evidence for NAIT. HPA-1a(−), 5b(−) platelets are obtained from accredited donors that have been shown to be negative for anticytomegalovirus antibodies, high titre anti-A and anti-B, other red cell antibodies, HPA-specific antibodies, HLA antibodies and, for female donors, granulocyte specific antibodies. This
Correspondence: Dr Geoff F. Lucas, PhD, FRCPath, Department of Histocompatibility and Immunogenetics, NHS Blood and Transplant, North Bristol Park, North Way, Filton, Bristol, BS34 7QH, UK. Tel.: +(44) 117 921 7536; fax: +(44) 117 912 5730; e-mail: [email protected]
© 2014 The Authors Transfusion Medicine © 2014 British Blood Transfusion Society
specification also enables these donors to donate platelets for intrauterine transfusion (IUT). These donors are typed for HPA1, -2, -3, -4, -5, -6, -9 and -15, which means that these donations also have the potential to support NAIT cases due to other antibody specificities, e.g. anti-HPA-3a. The accredited donors are also occasionally used to supply platelets for IUT in cases where there is foetal thrombocytopenia due to other causes, e.g. parvovirus infection. Until recently, platelet donations from accredited HPA1a(−), 5b(−) donors were identified with labels that were attached to luggage tags by staff in the donor collection centre. This meant that the 14 character donation number had to be manually transcribed up to 12 times – as would occur when a donor donated three adult doses of platelets because each adult dose had the potential to be split into four neonatal units. Manual labelling was labour intensive and always at potential risk of human error. This risk was partly mitigated by restricting the collection of HPA-1a(−), 5b(−) platelets to eight donor centres where there were a significant number of accredited donors and staff could become familiar with the labelling process. However, this prevented labelling of donations at sites where there were only a few accredited donors. On rare occasions, it has not been possible to supply HPA1a(−), 5b(−) platelets when required either because stock was held in a different holding location and could not be seen literally or electronically, because of a lack of donor availability or because of high demand (or due to a combination of these factors). Consequently, maintaining neonatal platelet stock levels often required intensive management, including asking donors to reschedule appointments at short notice and moving donations between centres to maintain minimum stock levels. In a few cases, it has been necessary to provide neonates with random platelets rather than HPA-1a(−), 5b(−) platelets. This is acceptable practice in severely thrombocytopenic infants at risk of bleeding prior to the arrival of HPA-1a(−), 5b(−) platelets and has been shown to provide satisfactory increments in some cases (Kiefel et al., 2006). However, random platelets can often be ineffective resulting in reduced increments and with a shorter halflife compared with HPA compatible platelets (Allen et al., 2007). In an attempt to address the problem of product availability, two major information technology (IT) based initiatives have been introduced. The first of these was to assign a blood characteristic (accredited HPA donor – ACHPA) to all active accredited HPA-1a(−), 5b(−) platelet donors so that the associated donations could be searched using the national blood component and donor management IT system (PULSE) and located anywhere in the country, irrespective of stock location. The
doi: 10.1111/tme.12108
128 Letter to the Editor • A total of 97 of 105 (92.4%) of donors made at least
• •
•
•
Fig. 1. Computer generated HPA-1a(−), 5b(−) label produced at validation. The label includes an eye-readable and barcode-readable donation number and the donor’s HPA genotype.
second initiative introduced computer controlled labelling so that a label is produced at product validation after all mandatory tests have been completed – in exactly the same way as for other blood components. The label produced identifies that the donation is HPA-1a(−), 5b(−) and provides the HPA genotype of the donor (HPA-1 to -5 and -15), see Fig. 1. The instruction to produce this label is centrally controlled by staff with responsibility for managing and monitoring donor accreditation. The introduction of computer controlled HPA-1a(−), 5b(−) labelling was introduced over a period of 10 months and five phases of work. Manual labelling was maintained as a ‘fail-safe’ procedure to ensure operational continuity. Phase 1 established that the labelling worked in practice and identified potential problems. Phase 2 introduced computer controlled labelling for donations collected from donor centres in Bristol, Oxford and Plymouth and was carefully monitored over a 10-week period to refine the new procedure. Phase 3 established that the labelling also worked in practice for platelet hyperconcentrate donations destined for IUT. Phase 4 introduced labelling for donations collected from donor centres in Lancaster, Liverpool and Manchester and later in the donor centres at Brentwood and Cambridge. In the fifth and final phase, the results of the project were reviewed and the manual labelling procedure was withdrawn in favour of the computer-based system. The key results of the project were as follows: • A total of 105 of 115 accredited donor records were
‘activated’ for computer labelling; the remaining 10 donors had been temporarily deferred.
REFERENCES Allen, D.A., Verjee, A., Rees, S., Murphy, M.F. & Roberts, R.J. (2007) Platelet transfusion in neonatal alloimmune thrombocytopenia. Blood, 109, 388–389.
Transfusion Medicine, 2014, 24, 127–129
one donation which was successfully computer labelled at validation. A total of 80 (76.2%) donors made two or more donations which were successfully computer labelled at validation. A total of 8 (7.6%) donor records were ‘activated’ but labels were not produced during the study period either because the donor did not attend after ‘activation’ or because the product was discarded prior to validation. At least three platelet hyperconcentrates were prepared using donations from accredited donors and labels were successfully produced. Donations from seven accredited donors who had moved to a different donor centre could be computer labelled thereby increasing the total number of accredited donors by 6% to 122.
These changes have increased the availability and awareness of HPA-1a(−), 5b(−) platelets because labelling is more secure and accredited donors can be recruited at additional donor collection sites. The donations are automatically labelled after product validation reducing manual intervention and increasing operational efficiency without the potential errors associated with manual transcription. Increased product availability combined with the ability to locate HPA-1a(−), 5b(−) platelets in different stock locations will result in improved clinical outcome for neonates with suspected NAIT.
ACKNOWLEDGMENTS GL planned and oversaw all the changes for this study and wrote the manuscript. NB made changes to and carefully reviewed the donor records and labelling and contributed to the manuscript. Many NHSBT staff contributed to the success of this work. We especially wish to thank: Helen Cerullo, Annmarie Endicott, Ann Green, Jeremy Kellington, Adrian Marsh, Edwin Massey, Nuru Mwandoro, Jessica Tovey, Stuart Penny, Julia Sault, Kelly Venus and David Winstone for their support.
CONFLICT OF INTEREST The authors have no competing interests. G. F. Lucas & N. Bendukidize Department of Histocompatibility and Immunogenetics, NHS Blood and Transplant, Filton, UK
Ghevaert, C., Campbell, K., Walton, J., Smith, G.A., Allen, D., Williamson, L.A., Ouwehand, W.H. & Ranasinghe, E. (2007) Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia. Transfusion, 47, 901–910.
‘Specifications for blood components’. In: Guidelines for the Blood Transfusion Services in the United Kingdom (Red Book) (8th edn). (2013) (ed. MaClennan S.), 7, Sections 29 & 30. The Stationery Office, Norwich.
© 2014 The Authors Transfusion Medicine © 2014 British Blood Transfusion Society
Letter to the Editor Kiefel, V., Bassler, D., Kroll, H. et al. (2006) Antigen – positive platelet transfusion in neonatal alloimmune thrombocytopenia (NAIT). Blood, 107, 3761–3763. Murphy, M.F. & Bussel, J.B. (2006) Advances in the management of alloimmune thrombocytopenia. British Journal of Haematology, 136, 366–378.
Murphy, M.F., Knechtli, C., Downie, C., Rogers, S.E. & Lucas, G.F. (2001) Serendipity and the use of random donor platelets in fetomaternal alloimmune thrombocytopenia (FMAIT). British Journal of Haematology, 113, 1076–1089. ‘Transfusion in antenatal obstetric and neonatal care’. In: UK Blood Transfusion and Tissue
© 2014 The Authors Transfusion Medicine © 2014 British Blood Transfusion Society
129
Transplantation Service Handbook (4th edn). (2007) (ed. MacLennan, D.B.L.) Section 6, p51–57. The Stationery Office, Norwich.
Transfusion Medicine, 2014, 24, 127–129
