Andrew Blann This chapter will outline: • the basics of blood grouping and variety of transfusion products • clinical assessment and management of patients requiring transfusion • the risks associated with blood transfusions • strategies to reduce the use of blood products perioperatively. The objective of blood transfusion has changed markedly over the decades, from being a crude instrument to maintain the haemoglobin level, to a targeted therapy to save lives. Additional changes have occurred following the realisation that blood transfusion is far from a simple and trouble-free treatment to one that can damage, possibly permanently, the health of the recipient. There are currently over two million packs of blood transfused each year in the UK, although changes in practice have brought this number down from nearly three million a decade ago. This decrease in usage is largely due to the reduced use of blood in surgical patients, with the widespread adoption of lower thresholds for transfusion than the haemoglobin level of 10g/dl that was traditionally quoted. It is often perceived that the majority of donated blood is transfused into patients undergoing surgery but recent studies show less than 40% of blood units are transfused into surgical patients. A further development has been the move from transfusing ‘whole’ blood, which therefore included plasma (with all its proteins, antibodies and other molecules), white blood cells and platelets, to transfusing only specific components, usually just the red blood cells. The latter, called ‘packed cells’, is not only more efficient, but also, without the white blood cells and plasma antibodies, produces fewer adverse reactions. The remaining plasma, once the red blood cells have been harvested, can provide other useful blood products (such as clotting proteins, although these can also be produced by genetic engineering). Laboratory staff can also help with albumin, fresh frozen plasma and transfusions of platelets (often needed by those at risk of, or with actual, haemorrhage) and, of course, a wealth of experience and advice. Why is blood transfusion needed? What do I need to do? Many possible reasons exist, but before we embark on the answers to these (and other) questions, a better understanding of the topic will be helpful. The major human blood groups are defined by the ABO system and the Rhesus (Rh) system. A patient’s blood group consists of two parts. First the blood group of a patient is determined by the presence or absence of specific ‘antigens’, molecules that are present at the surface of the cell. The presence or absence of an antigen is genetically determined, with the ABO locus being identified on chromosome 9, and these genomes code for specific glycoprotein, which is displayed on the cell surface. The second part relates to the presence or absence of specific antibodies. These are specialised proteins produced by lymphocytes and are thought to develop during the first year of life. The presence of these antibodies means that transfusion of blood containing specific blood antigens will lead to complement-mediated lysis of the red blood cell. Table 11.1 Determinants of ABO blood group
Chapter 11 The role of blood transfusion in preoperative assessment
The ABO system
This chapter will outline:
• the basics of blood grouping and variety of transfusion products
• clinical assessment and management of patients requiring transfusion
• the risks associated with blood transfusions
• strategies to reduce the use of blood products perioperatively.
The objective of blood transfusion has changed markedly over the decades, from being a crude instrument to maintain the haemoglobin level, to a targeted therapy to save lives. Additional changes have occurred following the realisation that blood transfusion is far from a simple and trouble-free treatment to one that can damage, possibly permanently, the health of the recipient. There are currently over two million packs of blood transfused each year in the UK, although changes in practice have brought this number down from nearly three million a decade ago.
This decrease in usage is largely due to the reduced use of blood in surgical patients, with the widespread adoption of lower thresholds for transfusion than the haemoglobin level of 10g/dl that was traditionally quoted. It is often perceived that the majority of donated blood is transfused into patients undergoing surgery but recent studies show less than 40% of blood units are transfused into surgical patients.
A further development has been the move from transfusing ‘whole’ blood, which therefore included plasma (with all its proteins, antibodies and other molecules), white blood cells and platelets, to transfusing only specific components, usually just the red blood cells. The latter, called ‘packed cells’, is not only more efficient, but also, without the white blood cells and plasma antibodies, produces fewer adverse reactions. The remaining plasma, once the red blood cells have been harvested, can provide other useful blood products (such as clotting proteins, although these can also be produced by genetic engineering). Laboratory staff can also help with albumin, fresh frozen plasma and transfusions of platelets (often needed by those at risk of, or with actual, haemorrhage) and, of course, a wealth of experience and advice.
Why is blood transfusion needed? What do I need to do? Many possible reasons exist, but before we embark on the answers to these (and other) questions, a better understanding of the topic will be helpful.
The major human blood groups are defined by the ABO system and the Rhesus (Rh) system. A patient’s blood group consists of two parts. First the blood group of a patient is determined by the presence or absence of specific ‘antigens’, molecules that are present at the surface of the cell. The presence or absence of an antigen is genetically determined, with the ABO locus being identified on chromosome 9, and these genomes code for specific glycoprotein, which is displayed on the cell surface. The second part relates to the presence or absence of specific antibodies. These are specialised proteins produced by lymphocytes and are thought to develop during the first year of life. The presence of these antibodies means that transfusion of blood containing specific blood antigens will lead to complement-mediated lysis of the red blood cell.
Table 11.1 Determinants of ABO blood group
|Blood group||Frequency (%)||Antigen structures on the red blood cell surface||Antibodies in the plasma|
|AB||3||A and B||None|
|O||46||None||Anti-A and anti-B|
Antigens A and B are protein structures with ‘sugars’ at the end that can be present on the surface of all body cells, including red blood cells. If you have only the blood group A structure on your red blood cells, you are blood group A. Similarly, if you have only group B molecules on your red cells then you are group B. People with both A molecules and B molecules on their red blood cells are group AB, and if you have neither of these structures on your red cells, you are group O.
We also have plasma antibodies that recognise blood group structures A and B, but in the healthy individual, these are the reverse of your blood group. So if you are group A, you will have antibodies that will recognise group B red cells (i.e. Anti-B). Likewise, group B people have antibodies that recognise group A red cells (i.e. Anti-A). Group AB people have no antibodies, but group O people have both anti-A and anti-B antibodies. Most people are blood group O, followed by group A. This is summarised in Table 11.1.
The Rhesus (Rh) system
The Rhesus system is more complicated, being composed of perhaps 48 recognised antigens, although practically, five different structures on the surface of the blood cell are commonly dealt with in the blood bank. A full explanation of this is beyond the scope of this chapter. However, in practice, focus is placed on the molecule known as D (i.e. Rhesus D), as it is this structure, and the antibodies that, if not correctly treated, give rise to haemolytic disease of the newborn (HDN). About 85% of white Europeans are Rhesus D positive. Other members of the Rhesus family of antigens are C, c, E and e.
The main distinction between the ABO and Rhesus systems is that in the normal person, there are always ABO antibodies to absent antigens. Anti-D antibodies are not normally found in blood, but these can easily be provoked by an incompatible transfusion or during childbirth. However, the fact that many of us naturally have anti-A and anti-B antibodies makes an ABO incompatibility potentially fatal.
Why order a blood transfusion?
Historically blood transfusions were requested to either maintain a patient’s haemoglobin at a specific level, commonly at greater than 10g/dl or in response to a volume of blood that was lost or envisaged to have been lost. Over the last two decades, this approach has been challenged and now the practitioner should consider the following questions:
• Does the patient really need it?
• What exactly is the clinical problem that requires resolution?
• Are there alternatives to resolve the problem rather than blood transfusion?
• Is iron therapy worth considering?
• Will erythropoietin be a possibililty?
• Would autologous transfusion be worth considering?
Common UK practice suggests that an otherwise seemingly healthy postoperative patient who has no particular symptoms, but has haemoglobin of 9g/dL, probably does not require a transfusion. As mentioned, historically a transfusion was often ordered simply because a physician considered it a good thing to do, with the belief that it would probably do the patient some good. This could, of course, be fine but this approach can lead to a number of problems.
• While the ABO/Rh systems are the most important blood groups, there are a host of other less frequent and (initially) less dangerous blood group antigens (with names such as Kidd, Duffy and Kell) that can cause a problem. The more transfused a person becomes, then the greater the likelihood that these problems will build up to become a real clinical and laboratory issue.
• We are programmed by evolution to collect and save iron in stores all over the body. People who are hyper-transfused often have problems in various organs as the build-up of this iron can cause damage to the tissues (a process called haemosiderosis). Since one unit of blood contains some 250mg of iron, 15 units can more than double the body iron stores.
• Transfused blood can contain pathogenic organisms (viruses, bacteria, parasites, nvCJD) although, through screening, this is becoming less of a problem.
• Infection can also occur via the site of the transfusion.
• Transfusion practice is not without errors as will be highlighted later.
Therefore, the present view is that transfusion should be reserved only for those in danger of losing their life, or for those who will show a measurable improvement not achievable by other means. It follows that the requirement for a transfusion can only be made clinically, not in the laboratory (by a particular haemoglobin result). The haematology laboratory provides the physician with this haemoglobin result, and the physician will then decide, after consideration of the patient’s state, whether or not the patient will benefit from a transfusion. However, much experience is available within the blood bank laboratory service and advice should be sought if cases fall outside established practice or guidelines.
Indications for blood transfusion
Reasons for ordering a transfusion can be many and varied, but major life-threatening indications include:
• chronic and serious anaemia unresponsive to other treatment, such as, severe cases of the haemoglobinopathies, sickle cell disease or thalassaemia
• life-threatening emergencies, such as rupture of an aortic abdominal aneurysm or massive blood loss after a road traffic accident
• haemorrhage, such as in haemophilia or because of overdoses of warfarin or heparin.
In surgery, there are other indications that need to be addressed.
• A curious response to many types of surgery is a fall in haemoglobin that cannot be accounted for by simple blood loss alone. This is presumed to have evolved to protect the body.
• Of course, if the operation is a ‘bloody’ affair, perhaps involving arteries or major organs, there may be significant blood loss, which needs to be replaced. However, blood volume can initially be replaced by an infusion of crystalloid or colloid intravenous fluids to maintain normal perfusion of organs.
However, transfusion should not be considered just because the haemoglobin result is less than a certain number. Various randomised controlled trials have failed to demonstrate any advantage of transfusing patients using an Hb trigger of 10g/dl compared to using lower triggers of between 7 and 8g/dl.
The mechanics of blood transfusion
Assuming the patient may need a transfusion, what are the next steps to be taken? Even before blood is taken, there must be an explanation of the process, and the patient’s consent must be obtained. We can view these in separate steps, although several may take place at the same time.
Explanation and consent
All patients undergoing operations, where there is a likelihood of receiving blood, must receive written information about blood transfusion. Information leaflets are available from the UK Transfusion Services (UKTS), though these should be tailored to provide local hospital-specific information depending on availability of services such as autologous transfusion (transfusion of patient’s own blood – see page 230). Information about blood transfusion is best given to patients at the time of preoperative assessment rather than on admission to hospital immediately prior to the operation.
Specific written consent is not currently required for blood transfusion in the UK but it is good practice to include mention of the possibility of transfusion in the consent for operation where there is a reasonable possibility of transfusion. These operations would be best defined as any operation where a ‘Group and Save’ or a ‘cross-match’ is routinely ordered. In addition, specific mention should be made on the consent form of any information leaflet given to the patient.
Once the requirement for a blood transfusion has been clarified, and the patient has received information and given consent, two allied blood tests are called for.
Group and Save
This is usually the first test that is done on the patient’s blood and allows the laboratory to identify the blood group of that particular patient, ideally in advance of their planned procedure. This is achieved with the request ‘Group and Save’ (GandS) – this instruction identifies the patient’s ABO blood group and often their Rhesus status (the ‘Group’ part of the process). The blood is then stored (the ‘Save’ part of the process, generally in a refrigerator) as this will be needed in the future to allow the laboratory to perform a ‘cross-match’. The ‘Save’ process may be time-limited and therefore, when planning a service, this time limit needs to be clarified to decide on the optimal time for taking blood from the patient.
Although the ‘Group and Save’ process identifies the patient’s ABO group and often their Rh status, administration of group-specific blood to a patient still puts that patient at risk of harm due to blood incompatibility. It is important therefore to match the blood group of the person needing the transfusion (the recipient) with the group of the blood that is to be transfused (the donor). This process is called a ‘cross-match’, and is done in the blood bank on a sample of the patient’s (recipient) anticoagulated or clotted blood – in the elective situation this sample will come from the specimen submitted for ‘Group and Save’.
The essential steps are:
(a) The patient must be ABO and Rh (D) typed – first part of the ‘Group and Save’ process.
(b) There must be screening for other clinically significant antibodies (this is as important as the cross-match).
(c) The actual ‘cross-match’ is where the patient’s plasma or serum is tested against a panel of potential blood from several different donors.
In practice, laboratory staff in the blood bank will mix red blood cells from the patient (recipient) with a series of plasma samples from stored bloods of five or six different donors, to see if there are any matches. Prior ‘Group and Save’ process allows the blood bank to identify the best possible matches and identify any other problems that may frustrate a good transfusion. Sometimes the laboratory may request a fresh blood sample from the patient, especially if the cross-match process is proving complicated due to the presence of numerous antibodies (common in patients who have received numerous blood transfusions).
A good match is where the red blood cells are unaltered by this mixing, and therefore should not react when in the patient. However, blood that does not match will aggregate, forming small clots, which indicates an incompatibility due to a cross-reaction with the red blood cell antigens and antibodies in the plasma. It is presumed that, if this mismatch blood is transfused, the same reaction may happen in the blood vessels of the recipient, which may kill them.
An example of this would be transfusing blood from someone of blood group A with some blood from someone of blood group B. The group A person has group A molecules on their red cells but also antibodies against B in the plasma (i.e. Anti-B). The group B person has the reverse – group B molecules on their red cells and anti-A antibodies in their plasma. So, when mixed, the group A red cells will be recognised by the anti-A antibodies, and so will react together. Similarly, the group B red blood cells will be recognised by the anti-B, and will also react. In an incompatible transfusion, the body has no way of knowing that the ‘foreign’ red bloods are actually being introduced to help the recipient.
Thus incompatibility is when the mismatched antibodies and red cells are mixed. One way of avoiding this is to always transfuse red blood cells which are group O and Rh negative – these cells lack antigens that the antibodies are designed to react towards, so there cannot be this kind of a problem with mismatching. Consequently, this ‘O-neg’ blood can be given to any patient in an emergency if cross-matching is not possible – hence it is a very valuable commodity. People who donate this kind of blood are called universal donors.
It follows that people who are Group AB do not have anti-A or anti-B antibodies in their plasma, so can receive A-neg, B-neg, O-neg or their own group (AB), and so are called universal recipients. However, they may still be susceptible to Rhesus and minor antigen reactions.
How much blood should be ordered?
Each healthcare organisation has developed a system, often called the Maximum Surgical Blood Ordering Schedule (MS-BOS), which determines the number of units of blood that will be needed for a particular operation. This is calculated from a review of average blood usage per type of operation over a reasonable period of time – this gives a figure which will determine the number of units required to be cross-matched for a given operation, usually cross-matching between one and two times the average number of units used per operation. For example, if an average of 1.4 units were used for a particular type of operation then two units would routinely be cross-matched. If an average of less than 0.5 units of blood were used for any type of operation, with only a minority of patients requiring blood, then a group and antibody screen (GandS) would usually be performed without any blood being routinely cross-matched preoperatively.
This MS-BOS system should be regularly reviewed and adjusted to allow for changes in surgical practice, which should be endeavouring to reduce perioperative blood loss if at all possible. The MS-BOS system, however, is only applicable to patients without any unusual red cell antibodies or increased risk of bleeding. If a patient has unusual antibodies, which may attack the incoming blood (normally fewer than 5% of routine surgical patients), then extra units are usually cross-matched, depending on the type of antibody. Similarly, in patients with increased risk of bleeding, cross-matching extra units of blood should be considered. Both of these situations require discussion between the surgical, anaesthetic and blood bank staff.
Risks of blood transfusions
The risk of blood transfusion in terms of morbidity and mortality is not clear, as invariably blood and its components are administered to patients with complex medical problems and in complex clinical situations. Patients may receive blood in a relatively stable situation and this transfusion may provide little or no clinical benefit, while when blood is administered during a life-saving operation the benefits are likely to far outweigh the risks.
The use of information from national reports of serious complications and transfusion-related deaths allows the practitioner to develop good practice to ensure that the risks to a patient are minimised. In the UK the Serious Hazard of Transfusion (SHOT) group (www.shotuk.org) produces annual reports of this information. The 2008 report found that of 1040 reported cases, with the issuing of 2,845,459 units of blood components in 2007–8 in the United Kingdom, there was one death reported as a direct consequence of the blood transfusion. There were 262 cases of incorrect blood transfused, in which 10 cases were due to ABO-incompatible red cell transfusion. Four of these cases were due to bedside administration errors, three due to ‘wrong blood in tube’ and three due to laboratory errors. The report also identifies 76 cases of inappropriate or unnecessary transfusion and 139 cases of handling or storage errors.
Clinical and laboratory problems in transfusion practice
Errors can and do occur at all places in the ‘journey’ from blood donor to blood recipient. However, it is generally recognised that most errors happen in the laboratory and/or once the blood has left the blood bank for its destination.
The packs of donor blood arrive from the National Blood Transfusion Service (NBTS) in good shape, having been typed for ABO and Rhesus, and screened also for major infective agents (hepatitis virus, HIV). However, the blood sample from the recipient may be labelled incorrectly. The next source of error may be the incorrect labelling of the small portion of each potential donor pack that is collected to take part in the cross-match.
Next, there may be error in the cross-match itself. These are very rare because the laboratory invests heavily in the technology and reagents to ensure that if an adverse reaction happens, it is detected. However, if the cross-match goes wrong, which is a false negative, a possibly incompatible unit of blood may be issued. If several packs are identified, the lab may assign an incompatible unit to the donor.
Post-laboratory errors are inevitably the wrong blood being given to the wrong patient. The wrong pack of blood may be collected from the blood bank issuing refrigerator, or the blood may be given in error to the wrong patient. A common confusion is that two or more patients are to be transfused at the same place at the same time, and that the bloods are switched.
Many of these are simply incorrect patient identification, generally by a misunderstood verbal recognition question, or by misreading the patient’s ID strip at the wrist. Effective checking is essential at all stages.
Prevention of transfusion reactions
Naturally, there are many steps designed to prevent a transfusion reaction: generally check, check and check again. Laser bar coding is being introduced so the sample can be traced from the requesting blood sample all the way back to the patient. Many hospitals have a policy of at least two members of staff checking the blood they are about to transfuse into one of their patients. This approach has proved to reduce mistakes and serious hazards of transfusion. Indeed, SHOT itself reports that ABO incompatible transfusions have shown a 54% reduction since 2001/2002. Blood transfusion outside core hours (mostly night time) is considerably less safe – and so it is a SHOT recommendation to avoid transfusion ‘out of hours’.
Many hospitals have their own formal policy, and professional bodies (e.g. the Royal College of Nursing, the Institute of Biomedical Sciences) generally offer guidelines. Checks must be made at each part of the pathway of the blood from the laboratory to the patient. These include:
• ensuring portering staff have collected the correct blood from the blood bank
• correct transfer of the blood to the requesting practitioner: the latter must take responsibility and sign the appropriate document
• if the transfusion is not immediate the blood must be placed in a blood-designated refrigerator to keep it cool – ideally blood should only be requested for immediate use
• finally, at the bedside, the details on the blood pack must be checked against the patient, not merely against the patient’s wristband, but also by confirming verbally (assuming the patient is conscious). These generally include name, sex, date of birth and hospital number and often home address.
The use of laser bar coding can help reduce errors that may arise. A further recent initiative is the requirement for a ‘cold chain’, which calls for blood being carried from the blood bank to the ward in cool bags. This is thought to be necessary for a number of reasons, such as to keep the blood cool and so reduce the opportunity for bacterial growth, and to maintain the integrity of the red cells.
There is a mandatory requirement that all blood must be traceable from ‘vein to vein’. Relevant documents include the EU Blood Safety Directive (2005/50). In the UK, the Medicines and Healthcare products Regulatory Authority (MHRA) is the EU-designated responsible authority to ensure all UK hospital blood banks are compliant.
Clinical management of transfusion problems
Adverse reactions to a blood transfusion may be classified as those happening within minutes or a few hours (that is, early reactions), and those happening perhaps after 12 hours to days later (that is, late reactions).
In an acute setting a transfusion reaction may not be easily diagnosed, as the patient may not recognise that there is a problem and the symptoms and signs of a transfusion reaction vary enormously (see Table 11.2).
Table 11.2 Symptoms and signs of early transfusion reaction