BLOOD TRANSFUSION

BLOOD PRODUCTS AND TRANSFUSION
24.18 FLUID RESUSCITATION IN CRITICALLY ILL PATIENTS
In patients in the ICU, use of either 4°r, albumin or normal salee v¬fluid resuscitation results in similar outcomes at 28 days.
* Finfer S, et al. Vex Sanguinis. 2004; 87 Suppl 2:5123-131.
24.19 RED CELL TRANSFUSION IN CRITICALLY ILL PATIENTS
In patients in intensive care, mortality and morbidity are similar or better in patients in whom Hb is maintained at 70-90 g/I than in those who received -twice as many red cell units to maintain Hb at 100-200 g/dl.
* Herbert PC, et al. N Engl J Med 1999; 340:409-417.
For further information: o www.transfusionguidelines.org.uk www.sign.ac.uk
Safe and effective clinical use of blood depends on:
• correct storage and handling throughout the life of the product right to the point of administration
• clinical protocols or guidelines for the management of patients at risk of transfusion
• a recorded assessment of the likely benefits and risks for each patient
• correct procedures for ordering and administration following the decision to transfuse.
 
A blood product is a therapeutic substance made from human blood. Transfusion may be needed when a patient has a deficiency or dysfunction of a blood constituent that causes symptoms or puts the patient at risk. It should only be prescribed if a useful improvement is likely to result. Patients who need transfusion require a safe and sufficient supply of blood. Transfusion from a donor is a form of allogeneic transplant and is never risk-free. Wherever possible, alternative treatments should be used (Boxes 24.18 and 24.19). For some patients, transfusion may be avoided by using strategies such as perioperative blood salvage or antifibrinolytic drugs.
A safe blood supply depends on a well-organised supply system that ensures regular donation by healthy individuals who have no excess risk of infections transmissible by blood. Every blood donation must be reliably tested to detect and exclude those containing transmissible agents. In the developed world, this includes hepatitis B, hepatitis C, HIV and human T lymphotropic virus (HTLV) which are detected with tests for antibody to the virus, viral antigen or nucleic acid. Platelet concentrates may be tested for bacterial contamination. The need for other microbiological tests depends on local epidemiology. For example, Chagas disease (p. 355) is transmissible by blood, and blood donations are tested for Trypanosoma cruzi in parts of South America where it is prevalent.
Effective control over the quality of safety testing, blood grouping, processing, storage and pre-transfusion testing of blood is also crucial. In the UK, blood services are licensed and regulated by the Pharmaceutical Regulatory Authority under European Union legislation. Figure 24.16 maps the main steps in blood collection, processing and storage.
BLOOD PRODUCTS
Blood products are subdivided as described below. In the UK, all blood components are processed to remove white cells. This is one of a number of precautions taken to minimise the risk of passing on the infective agent of variant Creutzfeldt-Jakob disease (vCJD, p. 1234) by transfusion, and blood donations are not accepted from individuals who have previously received a transfusion for the same reason.
Blood components are defined as whole blood or red cells, platelets, plasma or cryoprecipitate, prepared from single donations or by apheresis (Box 24.20).
Plasma derivatives are licensed pharmaceutical products produced from pooled human plasma obtained from many individuals. They are generally treated to remove or reduce virus contamination. Examples include the following:
• Coagulation factor concentrates factor VIII and IX for the treatment of conditions such as haemophilia and von Willebrand s disease. Coagulation factors made by recombinant DNA technology are preferred due to lack of infection risk.
• Intravenous immunoglobulin (IVIgG). This contains concentrated immunoglobulin and is used to replace IgG and reduce infective complications in hypogamma¬globulinaemia. It also modulates the immune response and is sometimes effective in immune thrombocytopenia (p. 1056) and Guillain-Barre syndrome (p. 1249). At present, there is no alternative to the plasma derivative. IVIgG can cause acute renal failure, especially in the elderly. Specific immunoglobulins to, for example,


 
 
 
Donor Education Recruitment Selection Donation
 
Plasma*
Fractionation
 
 
 
 
Plasma derivatives, e.g. albumin, immunoglobulin
Fig. 24.16 Blood donation, processing and storage. * In the UK, plasma for fractionation is imported as a precautionary measure against vCJD.
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hepatitis B, tetanus and varicella zoster are made from donors with high titres of antibodies to these, and are used to prevent the development of infection in exposed non-immune people.
0 Human albumin solution is available in two strengths. The 5% solution is indicated for replacement in plasma exchange. The 20% solution is used in the management of hypoproteinaemic oedema with nephrotic syndrome, and ascites in chronic liver disease. It is hyperoncotic and expands plasma volume by more than the amount infused.
RED CELL COMPATIBILITY
ABO RED CELL GROUPS
Transfusing red cells that have an ABO blood type that is incompatible with the recipient is the main cause of fatal, acute transfusion reaction.
There are four different ABO groups, determined by whether or not an individual s red cells express the A or B antigens. The frequency of ABO groups varies among
Testfor: HIV HTLV Hepatitis B Hepatitis C Syphilis ABO + RhD Other blood
groups Red cell antibodies
Process into blood components
Red cells Pooled platelets
Fresh frozen plasma
BLOOD PRODUCTS AND TRANSFUSION
24.20 BLOOD COMPONENTS  
 Properties Indications
Red cell components2 N.B. Red cell components must be compatible with To increase circulating red cell mass to relieve clinical
 the patient s ABO blood group features caused by insufficient oxygen delivery in patients
  with low Hb levels
Whole blood 450 ml donor blood collected into 63 ml anticoagulant/ Contains fibrinogen, other coagulation factors, and plasma
 preservative solution as a colloid volume expander. Whole blood is suitable for
 Stored at 2-6°C. Shelf life up to 5 weeks replacement of acute blood loss but red cell concentrates
  plus colloid or crystalloid are acceptable alternatives
Red cell concentrate Most of the plasma removed and replaced with a Most usual product in many countries, e.g. UK, US
 solution to optimise preservation of red cells Some restrictions on use in infants; otherwise suitable for
  any patient requiring red cell replacement
Platelet concentrate 3 One adult dose is made from four or five donations Treatment of bleeding due to thrombocytopenia and some
 of whole blood, or from a single platelet apheresis forms of platelet dysfunction
 procedure Prevention of bleeding due to thrombocytopenia in bone
 Stored at 20-24 C and must be agitated marrow failure
 Shelf life up to 5 days from collection 
 Platelets more effective if compatible with patient s 
 ABO type 
 Plasma in group 0 platelets can haemolyse red cells 
 of group A patient 
Plasma 150-300 ml plasma obtained from one donation Replacement of coagulation factor deficiency if a suitable
(Fresh frozen of whole blood. Shelf life usually 1 year licensed virus-inactivated product is not available, e.g.
plasma, FFP) Should be compatible with patient s ABO type multiple coagulation deficiencies in major haemorrhage
 Group 0 plasma particularly is at risk of causing Therapy of thrombotic thrombocytopenic purpura: by
 haemolysis in a groua A patient infusion or plasma exchange
  Do not use to replace circulatory fluid volume, to raise
  plasma albumin level or as an alternative to total parenteral
  nutrition
Virus-inactivated Plasma treated to reF- -_v` , r reduce infectivity of Indications as for FFP
plasma viruses from donor 
 Obtained from a pool of donors plasma treated with 
 solvent and detergettt or from single donations 
 treated with methylene blue and light 
Cryoprecipitate High molecular weight proteins are modesty Replacement of fibrinogen if a suitable licensed
 concentrated from plasma by precipitation near virus-inactivated plasma derivative is not available
 freezing point Used for von Willebrand disease and haemophilia if
 Each 10-20 ml pack of precipitate contains virus-inactivated or recombinant products not available
 fibrinogen. factor VIII and von Willebrand factor 
In the UK, all blood components are processed to reduce the leucocyte content to a level below 5 x 106 per pack.
2 Alternative oxygen-delivering fluids: perfiuorocarbon and haemoglobin solutions will NOT be licensed in the near future. 3 Platelet preparations treated to inactivate microbial pathogens are in clinical trial and may become available.
 
populations. Normal healthy individuals have antibodies (mostly IgM), from early childhood. against the A or B antigens that are not expressed on their own cells (Box 24.21). These anti-A or anti-B antibodies in the recipient s plasma will bind to transfused red cells that express A or B antigen, as follows:
• Anti-A reacts with red cells of group A or AB. v Anti-B reacts with red cells of group B or AB.
24.21 THE ABO SYSTEM  
Blood group Red cell A
or B antigens Antibodies in
plasma UK frequency ,
(%)
0 None Anti-A and anti-B 46
A A Anti-B 42
B B Anti-A 9 !
AB A and B None 3
ABO-INCOMPATIBLE RED CELL TRANSFUSION
If red cells of an incompatible ABO group are transfused, the patient s IaM antibodies bind to the transfused cells as above. This activates complement which damages the red cell membranes and causes lysis of the red cells. Fragments of ruptured cell membrane may initiate DIC and released haemoglobin may cause renal failure. The risk of a severe or
fatal reaction is greatest if group A red cells are infused to a
group O recipient.
THE RHESUS D BLOOD GROUP AND HAEMOLYTIC DISEASE OF THE NEWBORN
About 15% of Caucasians are Rhesus-negative: that is, they
lack the Rhesus D (RhD) red cell antigen. In other 1021
 
 
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BLOOD DISORDERS
populations only 1-5% may be Rhesus-negative: for example, in Chinese and Bengalis. IgG antibodies to RhD¬positive red cells are produced if such cells enter the circulation of an RhD-negative individual during pregnancy, via fetomaternal haemorrhage or transfusion. If a woman is so sensitised, during a subsequent pregnancy anti-RhD antibodies can cross the placenta and, if the fetus is RhD¬positive, severe fetal anaemia and hyperbilirubinaemia can result. This may cause severe neurological damage or death due to haemolytic disease of the newborn (HDN). Therefore an RhD-negative female who may subsequently become pregnant, should never be transfused with RhD-positive blood.
Anti-RhD immunoglobulin (anti-D) is the only effective product for preventing the development of Rhesus antibodies in RhD-negative women who are at risk. It acts by blocking the immune response to the RhD antigen. Anti-D is given after delivery and other potentially sensitising events during pregnancy. In some countries, routine prophylactic anti-D is recommended for all Rh-negative women in later pregnancy. There is no alternative to the human plasma derivative, although monoclonal antibody products are in development.
Other red cell antigen groups also may stimulate the development of red cell antibodies with the potential to cause haemolytic transfusion reactions or to cross the placenta and cause HDN. These include the other Rhesus antigens (RhC, c, E, e) and the Kell, Duffy and Kidd blood group antigens.
SAFE TRANSFUSION PROCEDURES
It is essential to ensure that no ABO-incompatible red cell transfusion is ever given. Such an accident is likely to kill or harm the patient and is avoidable. Errors leading to patients receiving the wrong blood are one of the main causes of mortality and morbidity due to transfusion. The patient s safety depends not only on correct pre-transfusion testing in the laboratory but also on the use of standard procedures for taking correctly labelled blood samples from the patient and for making sure that blood is infused into the correct patient. The proposed transfusion and any alternatives should be discussed with the patient, or if that is not possible with a relative, and this should be documented. Some patients, e.g. Jehovah s Witnesses, may refuse transfusion and require specialised management to survive profound anaemia following blood loss.
PRE-TRANSFUSION TESTING
The red cells from the patient s blood sample are tested to determine the ABO and RhD type. The patient s plasma is tested to detect any red cell antibodies that could haemolyse transfused red cells. This is done by checking the patient s serum for reaction against two or three different red cell types, specially selected to express the most important antigens. If the patient s serum contains an antibody to one of these, the red cells will agglutinate. The antibody can then be identified by further testing so that red cell units that lack the corresponding antigen can be selected.
The transfusion laboratory will perform either a `type and screen or a cross-match. In the `type and screen (or `group and hold or `group and save ) procedure, after testing as i above, the patient s sample is held in the laboratory for up  to a week. During this period, provided no antibodies have been detected, the hospital blood bank can prepare compatible blood for collection within about 15 minutes. In a further development of this approach (often called `electronic cross-match ) blood can be issued for suitable patients with no red cell antibodies on the basis of blood group information held in the laboratory s computer. In the cross-match (red cell compatibility testing) procedure, after pre-transfusion testing and a direct confirmation of compatibility ( cross-match ), red cell units are allocated to that patient for transfusion. Full cross¬matching takes about 45 minutes if no red cell antibodies are present, but may require hours or days if a patient has multiple antibodies, which is usually due to previous transfusions or pregnancies.
STANDARD PROCEDURES FOR PRE-TRANSFUSION SAMPLING AND ADMINISTERING OF TRANSFUSIONS
Most incompatible transfusions result from mistakes in taking or labelling the blood sample for pre-transfusion testing, or from failure to carry out standard checks before infusion to make certain the correct pack has been selected for the patient. Every hospital where blood is transfused should have a written transfusion policy that is used by all staff ordering and administering blood products.
It should give clear instructions on the following:
• Taking blood for pre-transfusion testing. Positively identify the patient at the bedside. Label the sample tube and complete the request form clearly and accurately after identifying the patient. Do not write forms and labels in advance.
• Administering blood. Positively identify the patient at the bedside. Ensure that the identification of each blood pack matches the patient s identification. Check that the ABO and RhD groups of each pack are compatible with the patient s. Check each pack for evidence of damage. If in doubt, do not use and return to the blood bank. Complete the forms that document the transfusion of each pack.
• Record-keeping and observations. The reason for transfusion, the product given, any adverse effects and the clinical response should be recorded in the notes. Transfusions should only be given in a situation where the patient can be observed. Blood pressure, pulse and temperature should be monitored before and
15 minutes after starting each pack. If the patient is conscious, further observations are only needed if the patient has symptoms or signs of a reaction. An unconscious patient should have pulse and temperature checked at intervals during the transfusion. Signs of abnormal bleeding during the transfusion could be due to DIC resulting from an acute haemolytic reaction.
ANAEMIAS
 
The UK haemovigilance study, SHOT, has collated reports of Serious Hazards of Transfusion for the years 1996-2003, during which about 23 million units of blood components were supplied. The incidence of adverse events reported (expressed per unit of blood supplied) is shown in Boxes 24.22 and 24.23.
Fever and allergic symptoms or signs, such as itch or urticaria, occur during about 1 % of transfusions, usually in patients who have had repeated transfusions. Usually these reactions are not serious but any new symptoms or signs that arise during a transfusion must be taken seriously as they may be the first warnings of a serious reaction. Infusion of fresh frozen plasma can rarely cause anaphylactic reactions.
Since it may be impossible to identify the cause of a severe reaction immediately, the initial supportive manage¬ment should generally cover all the possible causes. Figure 24.17 overleaf outlines the symptoms and signs, manage¬ment and investigation of reactions to blood products. Transfusion-associated graft-versus-host disease (TA GVHD) is a rare but always fatal complication. It occurs when there is sharing of an HLA haplotype between donor and recipient. Gamma irradiation of blood components prevents TA GVHD by preventing lymphocyte proliferation. Patients at risk of TA GVHD who must receive irradiated blood components include those with congenital T-cell immunodeficiencies, Hodgkin lymphoma, recipients of stem-cell transplants or blood from a family member, neonates and those treated with fludarabine (see www.transfusionguidelines.org.uk).
INFECT!
Over the past 30 years, the viruses that cause hepatitis B, AIDS and hepatitis C have been identified and effective tests introduced to detect and exclude infected blood units. Where blood is from `safe donors and correctly tested, the
24.22 INCIDENCE OF ADVERSE EFFECTS FROM
TRANSFUSION REPORTED TO SHOT  
• Wrong blood received 6.1 per 100 000
• ABO-incompatible blood received 1.0 per 100 000
• Transfusion-associated lung injury (TRALI) 0.6 per 100 000
• Transfusion-transmitted infections  
(mostly bacterial) 0.2 per 100 000
• Major morbidity 1.1 per 100 000
• Death probably due to transfusion 0.4 per 100 000
24.23 RISKS OF FATAL TRANSFUSION REACTIONS AS REPORTED TO SHOT
Data from the UK SHOT scheme estimates the risk of death at
- 0.4/100 000 blood component units supplied.The most common cause is transfusion of the wrong unit of blood leading to an incompatible red cell transfusion reaction and transfusion¬associated acute lung injury.
For further information: o www.shotuk.org www.transfusionguidelines.org.uk
ISIS TRANSMITTED BY TRANSFUSION
EBM
current risk of a donation being infectious is very small. In 2002-3 in the UK, the estimated chances that a unit of blood might transmit one of the viruses for which blood is tested, was 0.02 per 100 000 units for HIV, 0.005 for HCV and 0.24 for HB V More patients are put at risk by receiving an unintended blood component (6 per 100 000), including ABO-incompatible blood (1 per 100 000).
However, some patients who received transfusions before these tests were available have suffered very serious con¬sequences from these infections, and this is a reminder to avoid non-essential transfusions. Licensed plasma derivatives that have been virus-inactivated do not transmit HIV human T lymphotrophic virus (HTLV), HBV, HCV, cytomegalovirus or other lipid-enveloped viruses.
Several viruses that are transmissible by transfusion have recently been described, but have not been shown to be pathogenic. These include GBV-C (wrongly referred to as `hepatitis G ), TT virus and SEN-V They may prove to be `commensal agents.
There is great concern in the UK about variant Creutzfeldt-Jakob disease (vCJD), a human prion disease linked to bovine spongiform encephalitis (BSE, p. 1234). The risk of a recipient acquiring the agent of vCJD from a transfusion is uncertain, but of 16 surviving recipients of blood from donors who later developed the disease, one has died with clinical vCJD and another has died of unrelated causes but was found to have immunohistological signs of infection.
Bacterial contamination of a blood component may rarely occur, causing very severe and often lethal transfusion reactions. In the UK, 16 incidents with 9 fatalities were identified during the 5 years to 1999; about 80% of these occurred with platelet transfusion. Tests for contamination of platelet units may reduce the risk.
Transfusion-transmitted malaria is extremely rare in the UK and US but may be more important where malaria is prevalent. Donor selection procedures are designed to exclude potentially infectious individuals from donating red cells for transfusion. Blood testing for T. cruzi, in parts of South America where Chagas disease is endemic (p. 355), can reduce the risk of transmitting infection.