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- Herausgeber: John Wiley & Sons
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- Serie: ABC Series
- Sprache: Englisch
ABC of Transfusion
ABC of Transfusion
Blood services and Transfusion Medicine have become more clinical, scientific, well organised and consolidated over the last 20 years. More is known about the real frequency and aetiology of the hazards of blood transfusions. The ABC of Transfusion is a well-established introduction for all staff working in blood services, blood transfusion departments, surgical units and intensive care, and all prescribers and users of blood. It is a comprehensive, highly regarded guide to all the practical aspects of blood transfusion, including the various complications that can arise.
This fourth edition of ABC of Transfusion includes five new chapters on all the latest issues including pre-transfusion testing, vCJD, stem cell transplantation, immunotherapy, and appropriate use of blood – reflecting the fact that transfusion medicine has been revolutionised.
Useful as a practical guide, a refresher or for quick reference, it covers allessential transfusion matters and is an ideal source of information for all health professionals involved with safe and efficient use of blood.
About the ABC series
The new ABC series has been thoroughly updated, offering a fresh look, layout and features throughout, helping you to access information and deliver the best patient care. The newly designed books remain an essential reference tool for GPs, GP registrars, junior doctors and those in primary care, designed to address the concerns of general practitioners and provide effective study aids for doctors in training.
Now offering over 40 titles, this extensive series provides you with a quick and dependable reference on a range of topics in all the major specialities. Each book in the new series now offers links to further information and articles, and a new dedicated website provides you with even more support.
The ABC series is the essential and dependable source of up-to-date information for all practitioners and students in general practice.
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Veröffentlichungsjahr: 2013
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Contents
Contributors
Introduction
CHAPTER 1 The Blood Donor: Demographics, Donor Selection and Tests on Donor Blood
Demographics
Donor selection
Donation testing for markers of infection
Serological testing
Further reading
CHAPTER 2 Supply and Demand for Blood and Blood Components and Stock Management
The blood supply
Demand for blood components
Inventory management
The future
Further reading
CHAPTER 3 Compatibility Testing Before Transfusion; Blood Ordering and Administration
Ordering blood components and compatibility tests
Blood grouping and antibody screening
From the blood bank to the patient
Ordering blood for surgical operations
Adverse events
Further reading
CHAPTER 4 Red Cell Transfusion
Recipients of red cell transfusions
Preparation of red cells
Storage of red cell units
Rationale for the use of red cell transfusions
Effects of anaemia
Appropriate transfusion thresholds for red cell transfusion
Administration of red cells
Expected benefits of red cell transfusion
Adverse effects of red cell transfusions
Red cell transfusion in an emergency
Further reading
CHAPTER 5 Platelet and Granulocyte Transfusions
Preparation of platelet and granulocyte concentrates
Platelet transfusions
Granulocyte transfusions
Conclusion
Further reading
Reference
CHAPTER 6 Haemolytic Disease of the Newborn and its Prevention
Aetiology and pathogenesis of haemolytic disease of the newborn
Immunoprophylaxis
Preparation, dose and administration of anti-D Ig to RhD-negative women
Other red cell alloantibodies causing HDN
ABO haemolytic disease of the newborn
Blood grouping and antibody screening in pregnancy
Post-delivery tests
The future
Further reading
CHAPTER 7 Fetal and Neonatal Transfusion
Fetal transfusion
Neonatal transfusion
Conclusion
Acknowledgments
Further reading
References
CHAPTER 8 Plasma Products and Indications for Their Use
Fresh frozen plasma, cryoprecipitate and cryosupernatant
Plasma exchange
Factor VIII and IX concentrates
Recombinant factor Vila
Prothrombin complex concentrates
Other coagulation factor concentrates
Immunoglobulins
Other plasma products
Acknowledgments
Further reading
CHAPTER 9 Human Albumin Solutions and the Controversy of Crystalloids Versus Colloids
Physiology of albumin
Clinical properties of albumin
Clinical associations of serum albumin
Prognostic value of serum albumin
Indications
The crystalloid/colloid controversy and the suggestion that the use of albumin is associated with a higher mortality
Conclusion
Acknowledgments
Further reading
CHAPTER 10 Treatment of Massive Haemorrhage in Surgery and Trauma
Initial resuscitation phase
Later complications of massive haemorrhage
Survival from major haemorrhage
Acknowledgments
Further reading
CHAPTER 11 Immunological Complications of Blood Transfusion
Reactions to incompatible red cells
Reactions to incompatible white cells
Reactions to incompatible platelets
Reactions to plasma proteins
Immunomodulatory effects of transfusion
Further reading
CHAPTER 12 Infectious Complications of Blood Transfusion: Bacteria and Parasites
Properties of infections transmissible by transfusion
Screening tests for blood donations
Bacterial complications of transfusion
Other complications of transfusion
Conclusion
Further reading
CHAPTER 13 Infectious Complications of Blood Transfusion: Viruses
Hepatitis B virus
Hepatitis C virus
Human immunodeficiency virus
Adult T-cell leukaemia and human T-cell leukaemia virus
Cytomegalovirus
Parvovirus B19
Prion diseases
Conclusion
Further reading
CHAPTER 14 Variant Creutzfeldt–Jakob Disease and its Impact on the UK Blood Supply
Prion diseases
Transmission of vCJD by blood
Impact of vCJD on the UK blood supply
Further reading
CHAPTER 15 Risks of Transfusion in the Context of Haemovigilance: SHOT – the UK Haemovigilance System
How SHOT works
What have we learned from SHOT?
Making transfusion safer
Incorrect blood component transfused: what goes wrong and how it can be prevented
The role of information technology
A developing safety culture
The need for an overarching view of transfusion risks
Further reading
CHAPTER 16 Alternatives to Allogeneic Blood Transfusion
Preoperative preparation
Operative haemostasis
Autologous blood transfusion
Red cell salvage techniques
Antifibrinolytics
Topical haemostatic sealants
Recombinant factor VIIa
Further reading
CHAPTER 17 Blood Substitutes and Oxygen Therapeutics
Why is there a need for blood substitutes?
The search for an effective blood substitute
Potential blood substitutes
Conclusion
Further reading
CHAPTER 18 Appropriate Use of Blood and Better Blood Transfusion
History of the Better Blood Transfusion initiative in the UK
Evidence base for the appropriate use of blood and alternatives to transfusion
Audit as a tool to improve transfusion practice
Better Blood Transfusion activities
Future prospects for the Better Blood Transfusion initiative
Further reading
References
CHAPTER 19 Stem Cell Transplantation and Cellular Therapies
Haemopoietic stem cell transplantation
Cellular therapies
Stem cell plasticity and non-haemopoietic stem cells
Conclusion
Further reading
CHAPTER 20 Blood Transfusion in a Regulatory Environment and the EU Directives
Why is regulation needed?
Regulatory framework
Where next with regulation?
Further reading
References
Index
This edition first published 2009, © 2009 by Blackwell Publishing Ltd
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Library of Congress Cataloging-in-Publication Data
ABC of transfusion / edited by Marcela Contreras. -- 4th ed.p. ; cm. -- (ABC series)Includes index.ISBN: 978-1-4051-5646-2 (alk. paper)1. Blood--Transfusion. I. Contreras, Marcela. II. Series: ABC series (Malden, Mass.)[DNLM: 1. Blood Transfusion. WB 356 A134 2008]RM171.A23 2008615′.39--dc222007048168
A catalogue record for this book is available from the British Library.
1 2009
Contributors
Shubha AllardConsultant HaematologistRoyal London HospitalNational Blood ServiceLondon, UK
Trevor BaglinConsultant HaematologistAddenbrooke’s NHS TrustCambridge, UK
John BarbaraEmeritus Microbiology Consultant to the NHSBTColindale Centre, LondonandVisiting Professor in Transfusion Microbiology atthe University of West of EnglandBristol, UK
Liz CaffreyClinical Director – DonorsNational Blood ServiceCambridge, UK
Judith ChapmanManagerBlood Stocks Management SchemeLondon, UK
Hannah CohenConsultant HaematologistUniversity College London Hospitals NHS Foundation TrustLondon, UK
Marcela ContrerasChairman of Blood Transfusion InternationalProfessor of Transfusion MedicineRoyal Free and University College Hospitals Medical Schooland retiredNational Director of DiagnosticsDevelopment and ResearchNational Blood ServiceLondon, UK
Modupe ElebuteConsultant HaematologistSt George’s HospitalLondon, UK
Peter GarwoodManaging DirectorNational Blood ServiceBrentwood, UK
Patricia HewittConsultant Specialist in Transfusion MicrobiologyNational Blood ServiceElstree Gate, UK
Beverley HuntProfessor of Thrombosis and HaemostasisKing’s CollegeLondon, UKandDepartments of Haematology, Pathology and RheumatologyGuy’s and St Thomas’ Foundation TrustLondon, UK
James IronsideProfessor of Clinical NeuropathologyWestern General HospitalEdinburgh, UK
Sue KnowlesConsultant HaematologistEpsom and St Helier University Hospitals NHS TrustCarshalton, UK
Sailesh KumarConsultant Obstetrician and GynaecologistQueen Charlotte’s and Chelsea HospitalLondon, UK
Kenneth C. LoweAssociate Professor and Reader in BiotechnologySchool of Biology SciencesUniversity of NottinghamNottingham, UK
Brian McClellandScottish National Blood Transfusion ServiceEdinburgh, UK
Aleksandar MijovicConsultant in Transfusion MedicineKing’s College HospitalLondon, UK
Mike MurphyProfessor of Blood Transfusion MedicineConsultant HaematologistNational Blood ServiceJohn Radcliffe HospitalOxford, UK
Cristina NavarreteHead of Histocompatibility and ImmunogeneticsNational Blood ServiceLondon, UK
Helen V. NewConsultant in Paediatric Haematology and Transfusion MedicineSt Mary’s HospitalLondon, UK
Derwood PamphilonConsultant Haematologist and Honorary Clinical ReaderNational Blood ServiceBristol, UK
Fiona ReganConsultant Haematologist/Transfusion Medicine SpecialistHammersmith Hospital and National Blood ServicesLondon, UK
Angela RobinsonRetired Medical DirectorNHSBTWatford, UK
Neil SoniConsultant in Intensive CareChelsea and Westminster HospitalLondon, UK
Dorothy StainsbyConsultant in Transfusion Medicine and SHOT National MedicalCoordinatorNational Blood ServiceNewcastle, UK
Simon StanworthConsultant HaematologistNational Blood ServiceJohn Radcliffe HospitalOxford, UK
Clare TaylorConsultant HaematologistMedical Director, SHOTLondon, UK
Dafydd ThomasConsultant in Anaesthesia and Intensive TherapyMorriston HospitalSwansea, UK
Tim WalshConsultant Anaesthetist and Honorary ProfessorRoyal Infirmary of EdinburghEdinburgh, UK
Jonathan WallisConsultant HaematologistFreeman HospitalNewcastle, UK
Suzanne WattHead of Stem Cells and ImmunotherapyNational Blood ServiceOxford, UK
Introduction
In this era of super-specialization, it is difficult to find experts writing clearly about the basics of their specialties, making their subjects accessible to other doctors and healthcare workers. I feel that my collaborators have covered the fundamentals of transfusion medicine in an admirable, easy-to-read, comprehensible way.
This fourth edition of ABC of Transfusion has been expanded, with changes to previous chapters and four additional chapters to cover topics which are now established in transfusion medicine, such as haemovigilance, variant CJD, blood stocks management, appropriate use of blood and alternatives to allogeneic transfusion, as well as the increasing involvement of the regulatory environment. The wider breadth of the subject shows that this is not an area devoted exclusively to haematologists, but to all those colleagues collecting, processing and screening blood, prescribing blood components, preparing compatible safe blood for transfusion and administering it.
During my visits abroad in the last ten years, it has been rewarding to learn about the many colleagues worldwide who have encountered transfusion medicine for the first time when reading previous editions of ABC of Transfusion. Some of them have become leaders in the field as medical doctors, scientists, medical technologists, nurses, managers and marketers.
Blood transfusion continues to be life-saving in special situations, such as massive surgical haemorrhage, post-partum haemorrhage and severe malarial anaemia in young children. In addition, the safety of the blood supply and transfusion medicine have progressed considerably in the last few years. However, as the message from this book shows, we should only transfuse when the benefits outweigh the risks, yet we are still lacking evidence that blood transfusion works, or that it is the best therapy in a number of the clinical situations in which it is used.
I am grateful to the many colleagues who have contributed to this updated edition of ABC of Transfusion; they have patiently awaited its long gestation. I have no doubt that they, as well as the readers, will be satisfied with the outcome.
Professor Dame Marcela Contreras
CHAPTER 1
The Blood Donor: Demographics, Donor Selection and Tests on Donor Blood
Liz Caffrey, Patricia Hewitt and John Barbara
Demographics
In the UK all cellular and fresh frozen blood components are sourced from donations made by voluntary unpaid blood donors. A sufficient supply of components for transfusion to patients is therefore reliant upon these altruistic donors continuing to donate. Between 4% and 6% of the eligible adult population donate blood and, in 2005, 1.2 million English donors gave 2.1 million donations. The age range for regular whole blood donation is from 17 to 70 years. New donors are accepted up to their 66th birthday (Figure 1.1).
Donors come from all walks of life but are more commonly from social groups with stable, established lifestyles. Family tradition, peer pressure and personal or professional experience of transfusion are strong motivators.
In recent years it has become more difficult to maintain donor attendance at adequate levels to meet hospital demand. Donor numbers are falling despite heavy investment in recruitment and marketing activity. There are many reasons for this, but the pace of modern living and loss of community spirit are major factors.
Figure 1.1 Age profile of English donors, January 2005.
Others include lack of time, inadequate opportunities to donate, inconvenient venues and/or opening times, fear of needles and simple apathy. Lack of general awareness of the constant need for blood to support routine medical and surgical treatments is another factor. Volunteers flock to donate at times of ‘emergency’ but tend not to continue once the perceived need is over.
Donor selection
The possibility that donations might present a risk from transfusion transmissible infections or other conditions is minimized through two essential, complementary steps:
Decisions about donor acceptability and screening tests must take into account the characteristics of the donor population and the prevalence of infections transmissible by blood, the susceptibility of the recipient population, and any emerging risks. Two recent examples of the latter are variant Creutzfeldt–Jakob disease (vCJD) and West Nile virus.
Donor selection has two purposes: to protect the donor from harm and the recipient from any ill effects of transfusion. Potential donors should be provided with sufficient information to allow them to exclude themselves; they are required to read essential material before each donation (Figure 1.2).
Figure 1.2 National Blood Service blood safety leaflet. (Reproduced by kind permission of the National Blood Service.)
It is not practical to carry out a full medical examination on every volunteer. Therefore reliance is placed on simple visual assessment and answers to questions about general health, medical history and medication. These are administered using a questionnaire (Figure 1.3) and face-to-face structured interview with a trained member of staff. Confidentiality throughout this process is key to encouraging donors to provide truthful answers. All donors must give informed consent to donation and are required to sign to confirm this before every donation (Box 1.1).
Donor selection criteria
These have been developed and agreed throughout the UK for over 15 years. In November 2005, many selection criteria (particularly with respect to recipient safety) became legal requirements when the EU Blood Directive (2004/33/EC) was incorporated into UK statute (The Blood Safety and Quality Regulations 2005).
Donor safety
Donors must be in good health, within the permitted age range, and meet the minimum requirements for weight, donation volume, haemoglobin and donation frequency (Box 1.2).
The weight and donation volume limits protect the donor from giving more than 13% of their circulating blood volume, to minimize the risk of vasovagal reactions. The minimum haemoglobin levels ensure that: (i) the recipient receives an adequate amount of haemoglobin (minimum 40 g per unit transfused); and (ii) the donor is not rendered anaemic. Before each donation the haemoglobin level is assessed, usually by a simple, semiquantitative, gravimetric method using a drop of capillary blood introduced into a solution of copper sulphate of known specific gravity. This may be supplemented or replaced by the use of portable haemoglobinometers.
Where the potential donor’s medical history or medication indicate that the donor is not in good health or that their own health may be adversely affected as a result of donating, they are deferred either permanently (e.g. in cardiovascular disease) or temporarily (e.g. in pregnancy, anaemia or unexplained symptoms awaiting diagnosis).
Medications are rarely a cause per se to prevent donation but may indicate underlying pathology that requires the donor to be deferred.
Adverse effects of donation
Most donors suffer no ill effects. The most commonly reported problem is bruising and/or a painful arm. The overwhelming majority of these donors require only reassurance and simple first aid, unless complicated by infection or nerve injury. Approximately one in 75 donors feels faint during or shortly after donation and 15% of these suffer syncope (rarely serious unless associated with physical injury or slow recovery). These vasovagal symptoms are more common in younger, first time and female donors. Some donors report fatigue in the days following donation. Iron depletion may also occur and blood donation should be considered in the differential diagnosis of unexplained iron deficiency in regular donors.
Recipient safety
The most important consideration in the selection of donors is to avoid the transmission of infectious agents. The voluntary, unpaid status of UK donors contributes to patient safety as there is no financial incentive to conceal relevant details of medical or personal history. In addition, the fact that most UK blood donors are regular donors is an added safety factor.
Donors whose activities are known to be associated with an increased risk of acquiring infections are deferred temporarily for a period that exceeds the incubation period of the infection or, if there is a screening test which is routinely performed, that exceeds the window period for detection by routine screening tests. Deferral is permanent if the activities are ongoing or the infection is chronic, i.e. the volunteer is a carrier of a blood-borne agent. It is very important to exclude individuals whose behaviours are associated with a high risk of acquiring human immunodeficiency virus (HIV), hepatitis B or hepatitis C, and all donors are asked about these sensitive, personal issues each time they donate (Figure 1.4).
In addition, selection criteria take account of other known infectious risks as well as the small (theoretical) risk that may be posed by diseases of unknown aetiology (Box 1.3).
Figure 1.3 National Blood Service donor health check questionnaire, 2006. (Reproduced by kind permission of the National Blood Service.)
Donation testing for markers of infection
Most of the infections that are transmissible by blood transfusion and present a risk to recipients in the UK are characterized by unapparent, chronic or persistent infection. A blood donor therefore presents as healthy, but is capable of passing on infection through the blood. Examples include hepatitis B and C viruses (HBV and HCV, respectively), HIV and human T cell lymphotropic virus (HTLV). These infections are all characterized by the existence of a persistent viraemia, and can be detected by appropriate screening tests.
Figure 1.4 UK high risk exclusions as detailed on the National Blood Safety Service blood safety leaflet. (Reproduced by kind permission of the National Blood Service.)
Currently, UK blood donations are screened for the presence of:
hepatitis B surface antigen (HBsAg)
HIV infection, through the use of combined antibody/antigen detection tests with supplementary genomic testing on pools of samples for HIV RNA in some areas
HCV infection, through the use of tests to detect antibody supplemented by genomic testing for HCV RNA on pools of samples
HTLV, through testing for antibody on pools of samples
treponemal infection, through specific antibody detection assays.
All these tests are mandatory, and must be performed on every donation using nationally validated assays, with national ‘working standard’ samples and full process control.
Additional tests may be indicated for certain donors in particular circumstances. The necessity for these tests is usually decided after considering the epidemiology of the relevant infection and the risk presented from the local blood donor population. For instance, testing for antibodies to hepatitis B core (anti-HBc) is performed on donations in many developed countries, but it is not a routine screening test in the UK. It is used, however, for donors who have a higher risk of recent exposure to HBV infection through, for instance, skin piercing. It is also indicated for donors with a history of past HBV infection. A further example of such additional testing would be for evidence of malaria antibodies, as a marker of past exposure and possible continued infection. The decision whether to test depends upon a careful assessment of the potential donor’s travel and residence history. A combination of history taking, postponement of donation until some months after the last possible exposure, and a negative malarial antibody test should ensure that malaria is not transmitted by blood transfusion. A second parasitic infection, Chagas’ disease, is treated similarly.
There are other infections that may present a special risk to only a subset of transfusion recipients. An example is cytomegalovirus (CMV) infection, which is a particular hazard for immunosuppressed recipients. Despite routine leucodepletion of all UK blood components, which would be expected to substantially reduce the risk of transmission of cell-associated agents such as CMV, screening of selected blood donations continues to be performed to provide a supply of CMV ‘safe’ blood components for susceptible recipients. In areas of the world where CMV seroprevalence is very high, such a step would be impractical.
Despite careful blood donor selection and donation screening tests, infection may still be transmitted. Rarely, microbial agents that are not associated with persistent infection, and not therefore included in routine screening tests, can be transmitted by blood transfusion. This is usually because a donor gives blood during the incubation period, and examples have been reported for both hepatitis A and hepatitis E. Transmission of bacterial infection (unapparent donor bacteraemia) has also been reported on rare occasions but most bacterial transmissions are due to (exogenous) skin contaminants. Donation during the incubation period of an infection, i.e. during the ‘window period’ of infectivity, before reactive screening tests were developed, has also accounted for very small numbers of transmissions of those infections for which blood is now routinely screened, e.g. HIV.
Finally, there are infections for which there are no suitable screening tests; for the UK, vCJD is the most significant example. As virtually the whole of the UK population has been at risk of vCJD infection through diet in the past, the development of suitable blood tests and/or prion removal filters is proceeding (see Chapter 14). Thus, although blood transfusions in the UK are exceedingly safe, there still remains a very small risk of transmission of infection, and this fact reinforces the need for testing to be combined with careful donor selection.
Serological testing
Serological tests are carried out on all donations to ascertain the blood group (A, B, AB or O) and for RhD typing; the results are checked against those previously obtained from that donor or by repeat typing with different batches of antibodies and test cells. Most UK centres also test for RhC, c, e, E and K antigens, and this information appears on the blood pack label. Blood units found negative for D antigen are labelled ‘RhD negative’. With the monoclonal typing antibodies in current use, most weak and variant forms of D antigen are detected on direct testing. Those below the limit of detection with monoclonal anti-D are labelled as RhD negative since they are not considered to be immunogenic to a D-negative recipient. Extended testing to detect, for example, weak D or Du in donors is not universally carried out. A proportion of the units is also typed for Cw, Fya, Fyb, M, S, s, Jka and Jkb, thus making the phenotyped red cell stocks readily available for alloimmunized patients in need of transfusion.
All donations are screened for clinically important red cell antibodies. Any donation found to have a high antibody titre should not be used for transfusion, although it may be a valuable source of red cell typing reagent. Low titres of antibodies should not automatically exclude a donation from therapeutic use as the antibody would be further diluted on direct transfusion. As well as this, about 90% of the plasma (and hence antibodies therein) from most donations is removed and the cells are resuspended in an additive solution such as saline adenine glucose mannitol (SAG-M); most of the remaining red cells just have most of the plasma removed (see Chapter 4). The comparatively unrefined antibody screening, possible on automated blood grouping machines, is therefore acceptable in the testing of blood donations, although it is not acceptable in the screening for antibodies of samples from potential recipients. An exception to this is the selection of blood for ‘massive’ transfusion of a neonate, when donor blood should be screened for antibodies using sensitive techniques.
Testing of group O blood for high titre haemolytic anti-A, anti-B and anti-AB is still carried out in some centres in the UK, so that plasma-rich components, such as platelet preparations, can be appropriately labelled. This practice should not be allowed to override the principle that a patient should receive blood of his/her own group and that group O donor blood (especially plasma-rich components) should not be given to patients of other groups except in an emergency.
In England, typing for human leucocyte antigen (HLA) or histocompatibility antigens is carried out on regular plateletpheresis donors, to satisfy the demand for HLA-matched platelets. Such platelets are used in the treatment of a severely thrombocytopenic patient who, because of many exposures to blood components, has developed multispecific antibodies to HLA antigens and has become refractory to random platelet transfusions. Normally, HLA-compatible donors would provide one or two adult doses of platelets by means of plateletpheresis. Typing for human platelet antigens HPA-1a and HPA-5b is also performed on regular plateletpheresis donors to supply compatible platelets for the transfusion of fetuses and infants affected by neonatal alloimmune thrombocytopenia. Occasionally, HPA-typed platelets are required for the transfusion of immunologically refractory patients with anti-HPA.
Further reading
Barbara JAJ, Regan F, Contreras M. Transfusion Microbiology. Cambridge University Press, 2008.
Klein HG, Anstee DJ, Blood Transfusion in Clinical Medicine, 11th edn. Blackwell Publishing Ltd, 2005.
Murphy MF, Pamphilon DH (Eds). Practical Transfusion Medicine. Blackwell Publishing Ltd, 2001.
CHAPTER 2
Supply and Demand for Blood and Blood Components and Stock Management
Judith Chapman, Peter Garwood and Sue Knowles
Ability to meet the demand for blood and blood components is a primary goal of blood services, and is achievable through the good will of voluntary donors, effective inventory management and the appropriate use of blood and its alternatives by clinicians. The blood supply chain (Figure 2.1) includes the voluntary blood donor, the blood services, the hospital laboratory, the prescribing clinician and the recipient of blood. It is the responsibility of the blood services to minimize production loss and wastage and to employ good inventory management practice in conjunction with the hospital laboratories, whilst clinicians are responsible for prescribing blood only when there are no alternative approaches and the benefits exceed the risks. Blood is a freely given resource and a collaborative approach along the chain is required to ensure that it is available and used for the maximum benefit to patient care.
The blood supply
Volunteer donors are the source of the blood supply chain; however, the donor base continues to fall despite recruitment efforts. Research in England and North Wales indicates that the active donor base is shrinking. Although the risk from transfusion-transmitted infections has never been lower, the demand for safety through additional screening tests has never been greater. All additional testing for pathogens has the potential to lead to false positive reactions, and further donor deferrals and disqualifications.
Figure 2.1 The blood supply chain.
Figure 2.2 The leucocyte depletion process showing red cells undergoing filtration for leucocyte depletion.
The appreciation that variant Creutzfeldt–Jakob disease (vCJD) is likely to be transmitted through the blood supply has led to the exclusion of donors who have themselves been transfused and who are therefore particularly motivated to donate. Increased foreign travel and its associated risks of disease (e.g. malaria and West Nile virus) have also had an impact on the blood supply.
Whole blood donations (450 ml ± 10% of blood) are processed and converted into concentrated red cells and, according to requirements, platelet concentrates, fresh frozen plasma and cryoprecipitate.
In many developed countries, blood undergoes universal leucodepletion (Figure 2.2) for a number of reasons: to reduce the risk of transmission of vCJD, to remove leucocyte-associated viruses (e.g. cytomegalovirus or CMV), and to reduce other complications of transfusions related to the white cell content (e.g. the development of antibodies against human leucocyte antigen (HLA)) causing refractoriness to platelet transfusions or problems with future transplants. Following leucodepletion, concentrated red cells are resuspended in an additive solution to maintain red cell viability, to a final volume of 220–340 ml (Figure 2.3). In the UK, concentrated red cells may be stored for up to 35 days, at a controlled temperature range of 2–6°C. Changes that occur during storage include loss of viability, changes in metabolism, a reduction in pH, and an increase in potassium levels in the plasma.
Figure 2.3 Leucocyte-depleted red cells in additive solution.
Platelets can either be derived from whole blood donations or by pooling buffy coats from four whole blood donations or from single donor apheresis. In England and North Wales approximately 50% of preparations are prepared by apheresis and 50% from buffy coat pooling. Apheresis platelets are provided for recipients up to the age of 16 years, to reduce the risk of transfusion-transmitted infections by reducing donor exposure. An additional benefit of collecting apheresis platelets is that donors typed for HLA and human platelet antigens (HPAs) can be used to meet the requirements of patients with immunological refractoriness to random platelets and to cater for the specific requirements of intrauterine or neonatal transfusions in fetuses and infants suffering from alloimmune thrombocytopenia. Apheresis platelets undergo the same stringent testing procedures as whole blood donations.
Platelet concentrates (Figure 2.4) are stored in plasma (or platelet storage medium) at 20–24°C, normally for up to 5 days, and must be kept agitated. Platelets have a short lifespan due to loss of viability during storage and the potential for bacterial contamination. Consequently they have their own inventory management requirements. To ensure sufficiency over busy public holiday periods, additional supplies are required. However, with the potential for screening platelets for bacterial contamination prior to issue and the improved storage of leucodepleted platelets, the shelf life can be extended to 7 days to cover holiday periods.
Figure 2.4 Leucocyte-depleted pooled platelets.
Figure 2.5 Fresh frozen plasma pack.
Fresh frozen plasma (FFP; Figure 2.5) is sourced from both this country and the USA. The use of imported plasma reduces the risk of transfusion-transmitted vCJD and is transfused to recipients up to 16 years old. Imported plasma is also used exclusively for the manufacture of plasma products. Because the risk of viral-transmitted infections is lower in the UK donor population than in most other countries, imported FFP needs to undergo viral inactivation. FFP may also be virus inactivated, using either methylene blue (MB) or solvent detergent (SD) treatment. MB treatment can be applied to single packs, whereas SD treatment can only be applied to large pools of plasma. Both methods offer good virus protection but are associated with loss of coagulation factors. MB-treated virus-inactivated plasma imported from the USA is currently recommended for recipients up to the age of 16 years, while SD-treated plasma is reserved for patients with thrombotic thrombocytopenic purpura undergoing daily large volume plasma exchange.
Figure 2.6 Demand for red cells in England and North Wales, 2000–2007.
Demand for blood components
Demand is difficult to forecast for many reasons, since it follows the net effect of changes in population demographics and the degree of uptake of blood conservation strategies. Tools such as environmental scanning, mathematical modelling and trending can be used to try to forecast demand more accurately. The red cell demand forecast is used to calculate and set blood collection targets, which then form the basis for collection session planning.
There has been a decline in red cell demand in England over recent years and, despite an estimated blood donation rate of about 39 units per 1000 of the eligible donor population (the range for high Human Development Index (HDI) countries is 10.4–74.0), England and North Wales are self-sufficient in red cells. All requests for red cells from hospitals have been fully met by the National Blood Service over the last 6 years. In England and North Wales the demand for red cells has fallen year on year since 2000. In 2000/01 red cell demand was 2.22 million, but in 2006/07 had fallen to 1.87 million, a fall of 15.8% in 6 years (Figure 2.6). Lower demand may be attributable to a number of reasons including the publication of the Health Service Circular (HSC) 2002/09 Better Blood TransfusionII (see Chapter 18), the year on year increase in red cell prices, concerns over possible blood shortages, and the establishment of the Blood Stocks Management Scheme (BSMS) (Figure 2.7).
The use of blood during surgery has fallen significantly due to several factors, including improved surgical and anaesthetic techniques, treatment of correctable anaemias at pre-assessment clinics, the use of antifibrinolytic agents, intra- and postoperative cell salvage, and protocols for transfusion thresholds (see Chapter 16). However, successive audits still show considerable variability in the blood used for a given surgical procedure between different hospitals. An increasing proportion of red cells is transfused to medical and haemato-oncology patients, some of whom may be entirely transfusion-dependent. Erythropoietin may alleviate the anaemia in some categories of patients (e.g. lymphoproliferative disorders or following chemotherapy for solid tumours), but in the absence of recommendations from the National Institute for Health and Clinical Excellence few trusts have opted to fund it. Nevertheless, erythropoietin may reduce the demand for blood in some medical patients with chronic anaemia.
Figure 2.7 Blood Stocks Management Scheme website home page, http://www.bloodstocks.co.uk.
Inventory management
Different factors influence inventory levels in hospitals and blood services. Blood services need to balance the need to have sufficient stock to meet demand against having an excess of stock that leads to older red cells being issued and wastage due to time expiry. High red cell stock levels in the blood services leads to hospitals receiving blood that has a reduced shelf life, giving the hospital less time for the unit to circulate through the reserved/unreserved, stock/issue loop, thus increasing time expiry losses. The National Blood Service in England and North Wales has a policy of moving stock from centre to centre to ensure an equitable supply throughout the country. However, because of the lack of cold chain validation for the whole supply chain including the hospital, stock cannot currently be moved back from the hospital to the blood centre.
Hospitals also need to balance their inventory levels in order to have sufficient red cells to meet clinical demand but not an excess that leads to increased time expiry wastage. Several factors influence a hospital’s red cell inventory levels, including its size, the time taken for blood to arrive from the local blood centre, and the presence of specialist clinical units including trauma and orthopaedics.
