BLOOD TRANSFUSION

Blood transfusionShubha Allard

AbstractThe term ‘blood transfusion’ generally refers to the therapeutic use of

whole blood or its components (red cells, platelets, fresh frozen plasma

and cryoprecipitate). Careful donor selection and stringent testing by

the blood service is required to ensure a safe blood supply. Blood trans-

fusion may be essential for many clinical treatments where it can be life

saving. However, donated blood is a limited resource and hospital

blood transfusion practice must focus on ensuring safe and appropriate

use. Clinical guidelines are essential in all specialities using blood and

components, supported by education and training with regular audit of

practice. Particular emphasis must be placed on accurate patient identifi-

cation through the whole transfusion process from taking the initial blood

sample, through laboratory testing and the transfer of blood to clinical

areas to the final bedside check before transfusion to minimize errors.

The reporting and monitoring of all adverse events in relation to blood

transfusion via national haemovigilance schemes has highlighted key

areas for action resulting in improved transfusion safety. Transfusion

medicine must be practised within a strict regulatory framework; the Euro-

pean Union (EU) blood directives, in particular, have had far-reaching

implications for the UK blood services and for hospital transfusion

laboratories.

Keywords Better Blood Transfusion initiatives; blood components; EU

blood directive; haemovigilance; transfusion

Transfusion medicine has evolved over recent years with several

scientific and clinical advances. The introduction of more

advanced serological and molecular techniques for microbio-

logical testing and stricter criteria for selection of donors have

greatly reduced the risks of transfusion-transmitted infection

(Table 1). Additional steps during processing of blood and

components, including leucodepletion and, where feasible, viral

inactivation, have further improved safety.

The key priorities for clinical transfusion practice include

avoidance of unnecessary transfusion and reducing avoidable

transfusion errors wherever possible. A robust clinical gover-

nance infrastructure within a hospital, including an active

hospital transfusion team and hospital transfusion committee, is

essential for implementing key activities to ensure safe trans-

fusion practice and appropriate use of blood.

Blood donation and processing

Blood donation

All donors in the UK are unpaid volunteers. They are carefully

selected using a donor health questionnaire to ensure that they

can donate safely, and to exclude anyone at risk of transmitting

Shubha Allard MD FRCP FRCPath is Consultant Haematologist at Barts

Health NHS Trust and NHS Blood and Transplant, London, UK.

Competing interests: none declared.

MEDICINE 41:4 242

infection. Donors can give around 450 ml of whole blood up to

three times a year, which is separated into red cells, platelets and

plasma. UK plasma is no longer used for fractionation for

manufacture of blood products such as albumin, intravenous

immunoglobulin, anti-D or factor concentrates (see below).

Testing of donor blood

Transfusion-transmitted infection: the epidemiologyof infection in

the population of a particular country can help guide the testing

required to maximize safety of the blood supply. In the UK, all

donations are tested for syphilis, hepatitis B, hepatitis C, human

T-lymphotropic virus type 1 (HTLV1) and HTLV2 and human

immunodeficiency virus (HIV). Data available for 2008e2010, esti-

mating the risk of a potentially infectious unit entering the blood

supply in the UK, are shown in Table 1.

Where indicated by their travel history, donors are also tested

for malaria and Trypanosoma cruzi antibodies. Other discre-

tionary tests include anti-HBc (e.g. after body piercing). Some

donations are also tested for cytomegalovirus (CMV) antibody to

help provide CMV-negative blood for particular patient groups. In

the UK, the Advisory Committee on the Safety of Blood, Tissues

and Organs in the UK (SaBTO) has reviewed evidence available

and recommended that leucodepletion of all blood components

(other than granulocytes) provides adequate CMV risk reduction

for almost clinical situations, but CMV seronegative red cell and

platelet components should be provided for intra-uterine trans-

fusions and for neonates, and for pregnant women requiring

repeat elective transfusions during the course of pregnancy.

Variant Creutzfeldt-Jakob disease (vCJD): to date, there have

been three cases in the UK where blood transfusion may have

been implicated in transmission of vCJD and one case where an

abnormal prion was demonstrated at autopsy, in a patient who

did not have neurological symptoms but was known to have

received blood from a donor who subsequently developed vCJD.

A further transmission of vCJD prions was described in February

2009, in a patient with haemophilia who had received batches of

factor VIII to which a donor who subsequently developed vCJD

had contributed plasma. The patient died of other causes but was

found to have evidence of prion accumulation in his spleen.

There is no blood test currently available for detecting prions.

The full risk of vCJD in the UK population remains uncertain and

accordingly the UK blood services have taken a number of

precautionary measures to reduce the potential risk of trans-

mission of prions by blood, plasma and blood products, the latter

requiring fractionation of very large volumes of plasma. These

include:

� universal leucodepletion (removal of white cells) of all

blood donations since 1998

� importation of plasma for countries other than the UK for

fractionation to manufacture plasma products

� importation of fresh frozen plasma for use in children born

after January 1996

� exclusion of blood donors who have received a transfusion

in the UK since 1980.

Processing of blood

Donor blood is collected into plastic packs containing citric

phosphate dextrose, an anticoagulant that helps to support red

� 2013 Elsevier Ltd. All rights reserved.

Transfusion-transmitted infection in the UK: estimatedrisk in 2008e2010

Test Testing

introduced

Examples of testing

methods used

Approximate risk

of infection

Syphilis 1940s Antibody

Hepatitis B 1970

onwards

Surface antigen

(HBsAg)

1 in 1 million

HIV 1985/2002

onwards

Antibody/nucleic

acid testing

1 in 6 million

HCV 1991/1999

onwards

Antibody/nucleic

acid testing

1 in 72 million

HCV, hepatitis C virus; HIV, human immunodeficiency virus.

Table 1

BLOOD TRANSFUSION

cell metabolism. All units are then transported without delay to

the blood centre for processing, with initial leucodepletion to

remove white cells. Further processing is then undertaken to

produce red cells, platelets and plasma under stringent standards

of quality control.

The standard unit of red cells available in the UK has most of

the plasma removed and replaced by a saline solution containing

saline, adenine, glucose and mannitol (SAGM), also known as

optimal additive solution. Red cells are stored at 4�C with a shelf

life of 35 days.

An adult therapeutic dose (ATD) or one unit of platelets can

be produced either by single donor apheresis or by centrifugation

of whole blood followed by separation and pooling of the

platelet-rich layer from four donations suspended in plasma.

Platelets can be stored for 5 days at 20e24�C with constant

agitation to maintain optimal platelet function. Bacterial

screening of platelets before release can reduce the risk of

bacteriological contamination, with an extension of the shelf life

of platelet units to 7 days. Platelet components must not be

placed in a refrigerator.

Fresh frozen plasma (FFP) is produced by separation and

freezing of plasma at �30�C. In the UK, single donation units,

sourced from the USA and treated with methylene blue to reduce

microbial activity, are indicated for all children born after 1996.

Solvent-detergent plasma is prepared commercially from pools of

300e5000 plasma donations that have been sourced from non-

UK donors and treated with solvent and detergent to reduce

the risk of viral transmission.

Cryoprecipitate is prepared by undertaking controlled thawing

of frozen plasma to precipitate high-molecular-weight proteins

including factor VIII, von Willebrand factor and fibrinogen.

Cryoprecipitate consists of the cryoglobulin fraction of plasma

containing the major portion of factor VIII and fibrinogen. It is

obtained by thawing a single donation of FFP at 4�C � 2�C. Thecryoprecipitate is then rapidly frozen to e30�C. It is available as

pools of five units.

Blood transfusion regulation and the EU blood directives

The EU blood directive on blood safety set standards of quality

and safety for the collection, testing, processing, storage and

distribution of human blood and components. This was written

MEDICINE 41:4 243

into English Law as the UK Blood Safety and Quality Regulations

and was implemented in 2005.

Impact of blood safety and quality regulations in hospitals

The chief executive of each hospital with a transfusion laboratory

has to submit a formal annual statement of compliance to the

Medicines and Healthcare products Regulatory Agency (MHRA).

Hospital transfusion laboratories can be inspected by the MHRA

and, in the event of significant deficiencies, can be given the

order to ‘cease and desist from activities’. The key requirements

for hospitals include:

� a comprehensive quality management system based on the

principles of ‘good practice’, including stringent require-

ments for storage and distribution of blood and compo-

nents, with emphasis on ‘cold chain’ management

� traceability, requiring all hospitals to trace the fate of each

unit of blood/blood component (including name and

patient identification) with records being kept for 30 years

� education and training of staff involved in blood trans-

fusion, with maintenance of all training records

� haemovigilance, with reporting of all adverse events (see

below).

Hospital transfusion laboratories undertaking any processing

activities such as irradiation must have a licence from the MHRA

indicating blood establishment status.

Better Blood Transfusion (see Further Reading)

Although not a regulation, ‘Better Blood Transfusion’ health

service circulars published in 1998, 2002 and 2007 provide strong

recommendations for promoting safe transfusion practice within

hospitals, with particular emphasis on the appropriate use of

blood and components in all clinical areas.

All hospitals must have transfusion committees (HTCs), with

multidisciplinary representation. These committees are respon-

sible for overseeing implementation of guidelines, clinical audit,

and training of all staff involved in transfusion. The HTC has an

essential role within the hospital clinical governance framework

and must be accountable to the chief executive. The hospital

transfusion team (HTT), which comprises the transfusion nurse

specialist, transfusion laboratory manager and consultant hae-

matologist in transfusion, undertakes various activities on a day-

to-day basis to achieve the objectives of the HTC.

Patient Blood Management

Many of the above principles of the Better Blood Transfusion

initiatives have now been encompassed in Patient Blood

Management (PBM) an evidence-based, patient-focused initia-

tive, involving an integrated multidisciplinary multimodal team

approach, with the aims of optimizing the patient’s own blood

volume (especially red cell mass), minimizing the patient’s blood

loss, and optimizing the patient’s physiological tolerance of

anaemia, thereby reducing unnecessary transfusion.

Laboratory transfusion

Blood group serology e ABO groups

There are four different ABO blood groups, which are determined

by whether or not an individual’s red cells have the A antigen

(Group A), the B Antigen (Group B), both A and B antigens

(Group AB) or neither (Group O).

� 2013 Elsevier Ltd. All rights reserved.

BLOOD TRANSFUSION

Depending on theABOgroup, individuals produce anti-A or anti-

B antibodies in early life that are mainly immunoglobulin M (IgM)

andcan rapidly attackanddestroy incompatible cellswith activation

of the full complement pathway, resulting in intravascular hae-

molysis (acute haemolytic reaction). It is therefore essential that

only red cells of a compatible ABO group are transfused.

RhD group and antibodies

Individuals who lack the RhD antigen are called RhD-negative

and account for about 15% of the population, with the majority

who do have the RhD antigen called RhD-positive. RhD-negative

individuals can become ‘sensitized’ and develop anti-D after

being exposed to RhD-positive cells during transfusion or preg-

nancy. The clinical complications include haemolytic disease of

the newborn (HDN), the risk of which can be minimized by use

of anti-D immunoglobulin prophylaxis in RhD-negative mothers.

Transfusion of RhD-positive red cells to an RhD-negative indi-

vidual who is already sensitized can result in a ‘delayed trans-

fusion reaction’, in which the red cells become coated with IgG

and are removed by the reticulo-endothelial system by extra

vascular haemolysis. This can result in a failure of the haemo-

globin to rise together with jaundice.

There are around 300 human blood groups that belong to 30

separate red cell antigen systems as recognized by the Interna-

tional Society of Blood Transfusion. The ABO and RhD antigens

are particularly important but there are many other antigens on

red cells that may result in formation of antibodies following

pregnancy or transfusion, such as Kell, other Rh antigens (c, C, E

and e), Duffy antigens (fya, fyb), Kidd antigens (jka, jkb), and

these antibodies can also cause delayed transfusion reactions or

HDN.

Blood group and compatibility testing

The patient’s red cells are grouped for ABO and RhD type and the

plasma is tested for anti-A and anti-B antibodies. The majority of

laboratories in the UK now use automated blood grouping and

antibody testing with advanced information technology systems

for documentation and reporting of results.

Since errors related to having the ‘wrong blood in tube’ are

relatively common with potential risk of ABO mismatched

transfusions, the current British Committee for Standards in

Haematology (BCSH) guideline (2012) recommends that a

second sample should be requested for confirmation of the ABO

group of any new patient, provided this does not impede the

delivery of urgent red cells or components.

The hospital transfusion laboratory can readily provide red

cells that are ABO and RhD compatible using electronic issue (or

‘computer cross-match’), with no further testing needed,

provided the patient does not have any antibodies and that there

are robust automated systems in place for antibody testing and

identification of the patient. If a patient has red cell antibodies,

electronic issue should not be used and a full cross-match must

be carried out.

Special requirements

The hospital transfusion laboratory also needs to ensure that

appropriate blood and components are provided for patients with

special requirements such as CMV-negative blood (see above) or

irradiated blood. The latter is needed for immunocompromised

MEDICINE 41:4 244

patients to minimize risk of transfusion-associated graft-versus-

host disease. In addition to providing RhD-compatible blood, it is

important to avoid transfusing Kell-positive red cells to Kell-

negative girls and women with child-bearing potential, to

prevent formation of anti-K antibodies that can cause severe

HDN.

Certain patient groups, such as those with sickle cell disease,

are at very high risk of forming red cell alloantibodies, which

increases the risk of delayed haemolytic transfusion reactions.

Patients with haemoglobinopathy should therefore receive blood

that is matched for the patient’s full extended Rh type (c, C, D,

Ee) and K type, to prevent their forming antibodies to these

highly immunogenic antigens.

Clinical transfusion practice

All hospitals must have a transfusion policy with clear guid-

ance on correct patient identification and the safe administra-

tion of blood and components, including the detection and

management of adverse reactions. The National Patient Safety

Agency has issued a safe practice notice entitled Right Patient,

Right Blood, which states that all hospital staff involved in the

transfusion process, including phlebotomists, porters, medical

and nursing staff, must undergo training and competency

testing.

The decision to transfuse must be based on a thorough clinical

assessment of the patient and their individual needs, and the

indication for transfusion should be documented in the patients’

clinical records.

Errors in the requesting, collection and administration of

blood components (red cells, platelets and plasma components)

can lead to significant risks for patients. The Serious Hazards of

Transfusion (SHOT) scheme, launched in 1995, has shown

repeatedly that ‘wrong blood into patient’ episodes are an

important reported transfusion hazard; these are due mainly to

human error that can lead to life-threatening haemolytic trans-

fusion reactions and other significant morbidity.

All patients receiving a blood transfusion must wear an

identification band (or risk-assessed equivalent), with the

minimum patient identifiers including last name, first name, date

of birth and unique patient number. Positive patient identifica-

tion is essential at all stages of the blood transfusion process

including blood sampling, collection of blood from storage and

delivery to the clinical area and administration to the patient.

The detection and clinical management of acute transfusion

reactions is covered in Haematological Emergencies inMEDICINE

2013; 41(5) (Figure 1). Any adverse events or reactions related to

the transfusion should be appropriately investigated and reported

to local risk management, SHOT and the MHRA via the Serious

Adverse Blood Reactions and Events (SABRE) system.

Use of red cells: red cells are indicated to increase the haemo-

globin and hence the oxygen-carrying capacity of blood following

acute haemorrhage, or in chronic anaemia, with examples as

shown in Table 2.

There has been a trend in favour of lowering the haemoglo-

bin (Hb) threshold used as a ‘trigger’ for red cell transfusion

(e.g. Hb trigger of 7 or 8 g/litre for most patients with a trigger of

8 or 9 g/litre if there is a history of cardiac disease), but

� 2013 Elsevier Ltd. All rights reserved.

Patient exhibiting possible features of an acute transfusion reaction, which may include:fever, chills, rigors, tachycardia, hyper- or hypotension, collapse, flushing, urticaria, pain (bone, muscle, chest, abdominal),

respiratory distress, nausea, general malaise

STOP THE TRANSFUSIONUndertake rapid clinical assessment, check patient identification/blood compatibility label, visually assess unit

Evidence of:Iife-threatening Airway and/or Breathing and/or Circulatory problems and/or wrong blood given and/or evidence of contaminated unit

Yes No

Inform medical staffSEVERE/LIFE-THREATENING• Call for urgent medical help• Initiate resuscitation ABC• Is haemorrhage likely to be causing

hypotension? If not, discontinue transfusion (do not discard implicated unit/s)

• Maintain venous access• Monitor patient: e.g. TPR, BP, urinary

output, oxygen saturations

MODERATE• Temperature ≥ 39°C or rise ≥ 2°C and/or• Other symptoms/signs apart from pruritus/rash only

MILD• Isolated temperature

≥ 38°C or rise 1–2°C and/or

• Pruritus/rash only

• Consider bacterial contamination if the temperature rises as above and review patient’s underlying condition and transfusions history

• Monitor patient more frequently e.g. TPR, BP, oxygen saturations, urinary output

• Not consistent with condition or history

• Discontinue (do not discard implicated unit/s)

• Perform appropriate investigations

If consistent with underlying condition or transfusion history, consider continuation of transfusion at slower rate and appropriate symptomatic treatment

• Continue transfusion• Consider symptomatic

treatment (see text)• Monitor patient more

frequently as for moderate reactions

• If symptoms/signs worsen, manage as moderate/severe reaction (see left)

Continue transfusion

Document in notes that no HTT/HTC review/SHOT report necessary

Transfusion-related event

• Review at HTC• Report to SHOT/MHRA as appropriate

Transfusionunrelated

• If likely anaphylaxis/severe allergy, follow anaphylaxis pathway

• If bacterial contamination likely, start antibiotic treatment

• Use BP, pulse, urine output (catheterise if necessary) to guide intravenous physiological saline administration

• Inform hospital transfusion department

• Return unit (with administration set) to transfusion laboratory

• If bacterial contamination suspected, contact blood service to discuss recall associated components

• Perform appropriate investigations

Figure 1 Reproduced with kind permission of the British Committee for Standards in Haematology.

BLOOD TRANSFUSION

individual patient factors must be taken into account. The initial

assessment should include an evaluation of the patient’s age,

body weight and any co-morbidity that can predispose to

transfusion-associated circulatory overload (TACO), such as

cardiac failure, renal impairment or hypoalbuminaemia, and

fluid overload should be considered when prescribing the

volume and rate of transfusion, and in deciding whether

diuretics should be co-prescribed.

As a general guide, transfusing one unit of red cells gives an

Hb increment of 1 g/litre but only if applied as an approximation

for a 70e80-kg patient. The use of single unit transfusions in

small, frail adults (or prescription in ml, as for paediatric prac-

tice) is recommended.

MEDICINE 41:4 245

Blood for planned procedures

Patients undergoing surgery in which transfusion may be

required should have a group and screen sample taken in the

pre-operative assessment clinic. Providing the antibody screen

is negative, the transfusion laboratory can provide blood

components quickly as needed, without the need for reserving

cross-matched units. A maximum surgical blood-ordering

schedule (MSBOS) should be agreed. This specifies how many

blood units will be reserved (in the blood bank or satellite

refrigerator) for standard procedures, based on audits of local

practice.

Guidelines should also include strategies for blood conserva-

tion, including preoperative assessment (to detect and correct

� 2013 Elsevier Ltd. All rights reserved.

Use of red blood cells7

Acute haemorrhage, especially where >30% blood loss, following:

C surgery

C trauma

C childbirth

C gastrointestinal bleed

Bone marrow disorders causing anaemia, such as:

C myelodysplasia

C haematological malignancies (e.g. acute leukaemia, myeloma)

C bone marrow fibrosis

C bone marrow infiltration with secondary cancer

C aplastic anaemia

C chemotherapy/radiotherapy or bone marrow transplantation

Inherited anaemias:

C thalassaemia

C sickle cell anaemia (e.g. following stroke)

Haemolytic disease of the newborn

Autoimmune haemolytic anaemia

Table 2

BLOOD TRANSFUSION

iron deficiency anaemia or bleeding disorders) and cell salvage.

Routine preoperative autologous donation and storage of blood

prior to surgery is no longer recommended in the UK.

The use of erythropoietin is now well established in chronic

renal anaemia but the National Institute for Health and Clinical

Excellence does not support its routine use in patients with

anaemia secondary to cancer.

Use of platelets: platelets are indicated for the treatment or

prevention (prophylaxis) of bleeding in patients with thrombo-

cytopenia (low platelet counts) or with platelet dysfunction in

a number of situations (Table 3).

Indications for use of platelets

Situation

Bone marrow failure C To

o

Before invasive procedures C M

C M

C Ey

Massive blood transfusion (platelet count <50 x 109/litre

anticipated after 1.5e2 � blood volume replacement)

Aim t

Disseminated intravascular coagulation (DIC) C P

b

Platelet dysfunction C In

C A

Autoimmune thrombocytopenia Plate

Platelet transfusions are contraindicated in thrombotic thrombocytopenic purpura (T

Table 3

MEDICINE 41:4 246

Platelet refractoriness e a failure to obtain a satisfactory

increment to platelet transfusions may be due to immune or

non-immune causes. The main immune cause is human

leukocyte antigen (HLA) alloimmunization, which occurs

following previous pregnancy or transfusion. Non-immune

clinical factors include infection (and its treatment with anti-

biotics and antifungal drugs), disseminated intravascular

coagulation (DIC) and splenomegaly. HLA-matched platelet

transfusions are indicated if no obvious non-immune cause is

present and if HLA antibodies are detected.

Use of fresh frozen plasma and cryoprecipitate: there is a lack

of good evidence for the clinical use of FFP. In adults, the

therapeutic dose of FFP is 12e15 ml/kg body weight. FFP is

indicated in patients with acute DIC in the presence of bleeding

and abnormal coagulation results (see Acquired Disorders of

Coagulation on pages 228e230 of this issue). Solvent-detergent

treated plasma is indicated for patients undergoing plasma

exchange for thrombotic thrombocytopenic purpura. In the UK,

all children born after 1996 should receive non-UK sourced

plasma as a CJD risk reduction measure, methylene blue treated.

FFP sourced from outside the UK is available for paediatric use.

FFP should not be used for reversal of oral anticoagulation

(warfarin), where the use of prothrombin complex (prothrombin

complex concentrate) is indicated (BCSH anticoagulation guide-

lines) (see Acquired Disorders of Coagulation on pages 228e230

of this issue). The coagulopathy of liver disease is also complex,

with many studies showing the lack of evidence of clinical

benefit of prophylactic FFP transfusion in this setting.

The main indication for use of cryoprecipitate is in massive

haemorrhage for replacement of fibrinogen, where the concentra-

tion is below 1.5 g/litre. The adult dose is two pools of cry-

oprecipitate with five units in each pool.

Cryoprecipitate must not be used for replacement of coagu-

lation factors in inherited conditions such as haemophilia or

von Willebrand’s disease, since specific factor concentrates are

available for the treatment of these conditions.

prevent spontaneous bleeding when platelet count <10 � 109/litre

r <20 � 109/litre if there is an additional risk (e.g. sepsis)

inor surgery or procedures e raise platelet count to >50 � 109/litre

ajor surgery >80 � 109/litre

e surgery or neurosurgery >100 x 109/litre

o maintain platelet count >75 � 109/litre

latelet transfusion indicated in acute DIC if low platelets and bleeding

ut not in chronic DIC without bleeding

herited e Glanzmann’s thrombasthenia

cquired e antiplatelet drugs (e.g. aspirin and clopidigrel)

let transfusions should be used only if major haemorrhage present

TP).

� 2013 Elsevier Ltd. All rights reserved.

BLOOD TRANSFUSION

Patient information and consent

The last Better Blood Transfusion 1998, 2002 and 2007 health

service circular recommends that timely information should be

made available to patients, informing them of the indication for

transfusion, the risks and benefits of blood transfusion, and any

alternatives available. There is also a need to increase patient

awareness regarding the importance of correct identification.

In October 2011, the Advisory Committee for the Safety of

Blood, Tissues and Organs (SaBTO) in the UK re-enforced the

recommendation that valid consent for blood transfusion should

be obtained and documented in the patient’s clinical record by

the healthcare professional. A standardized information resource

for clinicians, indicating the key issues to be discussed by the

healthcare professional when obtaining valid consent from

a patient for a blood transfusion, is now available at: http://

www.transfusionguidelines.org.uk/index.asp?Publication¼BBT

&Section¼22&pageid¼7691 A

FURTHER READING

BCSH. Guidelines for the use of fresh frozen plasma, cryoprecipitate and

cryosupernatant. Br J Haematol 2004; 126: 11e28.

BCSH. Guidelines for the use of platelet transfusions. Br J Haematol2003;

122: 10e23.

MEDICINE 41:4 247

Better Blood Transfusion e safe and appropriate use of blood.

HSC2007/001. In: McLelland DBL, ed. Handbook of transfusion

medicine. 4th edn. London: HMSO, 2007.

British Committee for Standards in Haematology (BCSH). Guideline on the

Administration of Blood Components, http://www.bcshguidelines.com;

2009.

British Committee for Standards in Haematology (BCSH). Guideline on the

investigation and management of acute transfusion reactions. Br J

Haematol 2012; 159: 143e53.

British Committee for Standards in Haematology (BCSH). Guidelines for

pre-transfusion compatibility procedures in blood transfusion labo-

ratories, http://www.bcshguidelines.com; 2012.

British Committee for Standards in Haematology (BCSH) Guidelines. The

clinical use of red cell transfusion. Also available at: http://www.

bcshguidelines.com.

Health Protection Agency. NHSBT/HPA Infection Surveillance Reports. Also

available at: www.hpa.org.uk.

National Patient Safety Agency. London: HMSO. Also available at: http://

www.npsa.nhs.uk; 2007.

Serious Hazards of Transfusion: http://www.shotuk.org.

The Medicines and Healthcare products Regulatory Agency. Also available

at: http://www.mhra.gov.uk.

UK Blood Transfusion and Tissue Transplantation Services. Guidelines for

the blood transfusion services in the UK (RedBook). 7th edn. London:

HMSO. Also available at: www.transfusionguidelines.org; 2005.

� 2013 Elsevier Ltd. All rights reserved.