BLOOD TRANSFUSION

Blood transfusion

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).

Shubha Allard

Testing of donor blood

Transfusion-transmitted infection: the epidemiology of 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, estimating 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 discretionary 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 transfusions and for neonates, and for pregnant women requiring
repeat elective transfusions during the course of pregnancy.

Abstract
The 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 transfusion 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 identification 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 European 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

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 transmission 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.

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 microbiological 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 governance infrastructure within a hospital, including an active
hospital transfusion team and hospital transfusion committee, is
essential for implementing key activities to ensure safe transfusion 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

Processing of blood
Donor blood is collected into plastic packs containing citric
phosphate dextrose, an anticoagulant that helps to support red

Shubha Allard MD FRCP FRCPath is Consultant Haematologist at Barts

Health NHS Trust and NHS Blood and Transplant, London, UK.
Competing interests: none declared.

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BLOOD TRANSFUSION

into English Law as the UK Blood Safety and Quality Regulations

and was implemented in 2005.

Transfusion-transmitted infection in the UK: estimated

risk in 2008e2010
Test

Testing
introduced

Examples of testing
methods used

Syphilis
Hepatitis B

1940s
1970
onwards
1985/2002
onwards
1991/1999
onwards

Antibody
Surface antigen
(HBsAg)
Antibody/nucleic
acid testing
Antibody/nucleic
acid testing

HIV
HCV

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 requirements for storage and distribution of blood and components, 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 transfusion, 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.

Approximate risk
of infection

1 in 1 million
1 in 6 million
1 in 72 million

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

Table 1

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 nonUK 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. The
cryoprecipitate is then rapidly frozen to e30 C. It is available as
pools of five units.

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 responsible 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 haematologist in transfusion, undertakes various activities on a dayto-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 initiative, involving an integrated multidisciplinary multimodal team
approach, with the aims of optimizing the patients own blood
volume (especially red cell mass), minimizing the patients blood
loss, and optimizing the patients 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 individuals red cells have the A antigen
(Group A), the B Antigen (Group B), both A and B antigens
(Group AB) or neither (Group O).

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

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Depending on the ABO group, individuals produce anti-A or antiB antibodies in early life that are mainly immunoglobulin M (IgM)
and can rapidly attack and destroy incompatible cells with activation
of the full complement pathway, resulting in intravascular haemolysis (acute haemolytic reaction). It is therefore essential that
only red cells of a compatible ABO group are transfused.

patients to minimize risk of transfusion-associated graft-versushost disease. In addition to providing RhD-compatible blood, it is
important to avoid transfusing Kell-positive red cells to Kellnegative 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 patients full extended Rh type (c, C, D,
Ee) and K type, to prevent their forming antibodies to these
highly immunogenic antigens.

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 pregnancy. 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 individual who is already sensitized can result in a delayed transfusion 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 haemoglobin 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 International 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.

Clinical transfusion practice

All hospitals must have a transfusion policy with clear guidance on correct patient identification and the safe administration 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 transfusion 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 identification 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 in MEDICINE
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.

Blood group and compatibility testing

The patients 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.

Use of red cells: red cells are indicated to increase the haemoglobin 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 haemoglobin (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

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

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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 TRANSFUSION
Undertake 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

SEVERE/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

Inform medical staff

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

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

MILD
Isolated temperature
38C or rise 12C
and/or
Pruritus/rash only

Consider bacterial contamination if the

temperature rises as above and review
patients underlying condition and
transfusions history
Monitor patient more frequently e.g. TPR, BP,
oxygen saturations, urinary output

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)

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

Transfusion-related
event

Transfusion
unrelated

Continue transfusion

Document in notes that

no HTT/HTC review/SHOT
report necessary

Review at HTC
Report to SHOT/MHRA as appropriate

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

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 conservation, including preoperative assessment (to detect and correct

individual patient factors must be taken into account. The initial

assessment should include an evaluation of the patients 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 practice) is recommended.

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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 antibiotics 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 red blood cells7

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

surgery
trauma
childbirth
gastrointestinal bleed

Bone marrow disorders causing anaemia, such as:

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
C

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 guidelines) (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 concentration is below 1.5 g/litre. The adult dose is two pools of cryoprecipitate with five units in each pool.
Cryoprecipitate must not be used for replacement of coagulation factors in inherited conditions such as haemophilia or
von Willebrands disease, since specific factor concentrates are
available for the treatment of these conditions.

Inherited anaemias:
thalassaemia
C
sickle cell anaemia (e.g. following stroke)
C

Haemolytic disease of the newborn

Autoimmune haemolytic anaemia
Table 2

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 thrombocytopenia (low platelet counts) or with platelet dysfunction in
a number of situations (Table 3).

Indications for use of platelets

Situation
Bone marrow failure
Before invasive procedures

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

anticipated after 1.5e2  blood volume replacement)
Disseminated intravascular coagulation (DIC)
Platelet dysfunction
Autoimmune thrombocytopenia

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

or <20  109/litre if there is an additional risk (e.g. sepsis)
C
Minor surgery or procedures e raise platelet count to >50  109/litre
C
Major surgery >80  109/litre
C
Eye surgery or neurosurgery >100 x 109/litre
Aim to maintain platelet count >75  109/litre
C

Platelet transfusion indicated in acute DIC if low platelets and bleeding

but not in chronic DIC without bleeding
C
Inherited e Glanzmanns thrombasthenia
C
Acquired e antiplatelet drugs (e.g. aspirin and clopidigrel)
Platelet transfusions should be used only if major haemorrhage present
C

Platelet transfusions are contraindicated in thrombotic thrombocytopenic purpura (TTP).

Table 3

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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 laboratories, 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.

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 patients 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?PublicationBBT
&Section22&pageid7691
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.

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