Blood transfusion in children with

haematological/oncological disease










Haemato-Oncology (Schiehallion) Unit
Royal Hospital for Sick Children, Yorkhill
Women & Childrens Directorate


















Blood Transfusion Version: 1.1 Page 1 of 7
Author: Dr B Gibson Authorised by: Schiehallion
group
Issue Date: September 2006
Date of Review: September 2008 Q-Pulse Ref: YOR-Haem-001


Blood Transfusion Version: 1.1 Page 2 of 7
Author: Dr B Gibson Authorised by: Schiehallion
group
Issue Date: September 2006
Date of Review: September 2008 Q-Pulse Ref: YOR-Haem-001

Contents Page Number(s)
1. General Principles of Transfusion 2
2. Specification of Blood and Blood Products 2 - 4
3. Indications for Transfusion 4 - 6
4. Transfusion Reactions 7 - 8

1. General Principles of Transfusion
There is a Hospital Transfusion Policy with which everyone involved with the
transfusion process should be familiar.

The commonest error in the transfusion procedure is the transfusion of a blood
component or plasma product that does not meet the appropriate requirements
of the patient or which was intended for another patient. Both medical and
nursing staff should be familiar with the recommended specification for blood and
blood components in paediatric practice and should be scrupulous about accurate
patient identification.

Children with haematological/oncological disease are amongst the most
frequently transfused patients at RHSC and it is important to minimise their
exposure to blood and blood products wherever possible.

The EU Directive on Blood Safety requires that the fate of all units of blood and
blood products be traceable. Therefore the indication for the transfusion of every
unit of blood or blood product should be documented in the patients casenote
with the volume transfused and the unique unit identifier.

Medical and nursing staff involved in the transfusion process should know how to
recognise, manage and investigate a transfusion reaction.


2. Specification of Blood and Blood Products
It is the responsibility of the doctor ordering the blood or blood product to be
familiar with the specific requirements for any individual patient and to make sure
that the blood or blood product ordered meets these.

Blood Group:
Stem Cell Transplant (SCT) Patients
Recipients of stem cell transplants may be of a different blood group to their
donor and this can lead to a major or minor mismatch. The patients transplant
schedule will clearly state the blood group(s) of red cells, platelets and FFP that
should be transfused. The transplant schedule should always be checked and the
instructions followed.

Haemoglobinopathy and Bone Marrow Failure Syndrome Patients
These patients may be regularly transfused throughout life and, because of this,
are extensively red cell phenotyped to minimise the risk of allo-immunisation.
Their red cell phenotype should be documented in their casenote. The Blood Bank
will require advanced warning to provide appropriate blood.

IRRADIATED BLOOD AND BLOOD PRODUCTS:
All blood is now leucodepleted by the Scottish National Blood Transfusion Service
(SNBTS) immediately after donation to prevent the transmission of variant CJD.
However, even the very small number of white cells that remain after
leucodepletion can engraft in severely immunocompromised recipients and cause
Blood Transfusion Version: 1.1 Page 3 of 7
Author: Dr B Gibson Authorised by: Schiehallion
group
Issue Date: September 2006
Date of Review: September 2008 Q-Pulse Ref: YOR-Haem-001

Transfusion Associated Graft Versus Host Disease (TAGVHD), which is usually
fatal. In normal immunocompetent recipients these white cells are cleared by the
immune system and cause no clinical problems. Irradiation of blood and blood
products prevents the proliferation of transfused white cells in the recipient and is
universally effective in preventing TAGVHD. Table 1 lists some of the patient
categories that require irradiated blood products and these include:
All transplant patients (allogeneic and autologous), all patients
receiving Fludarabine containing regimens, all patients with
Hodgkins disease, all patients with or suspected of having
congenital immunodeficiency and all patients with Di George
syndrome or those undergoing cardiac surgery who may have Di
George syndrome
All platelet and granulocyte transfusions are routinely irradiated
by the SNBTS.
FFP contains very few white cells but has been reported to have
caused TAGVHD in congenital immunodeficiency and FFP should be
irradiated in this setting only.


CMV NEGATIVE BLOOD AND BLOOD PRODUCTS:
Leucodepletion significantly reduces the risk of transfusion related CMV
transmission. However, the British Clinical Standards for Haematology still
recommend that CMV negative products be transfused to SCT recipients. They
also recommend that CMV screened products be used for IUT, ET and infants
weighing <1.5kg.The evidence for the latter is weak and should not result in
unnecessary delay in transfusing platelets to the infant.

Table 1: Specification of Red Cells & Platelets
Irradiation CMV Negative
Children aged < 1 year No Yes
Suspected immunodeficiency (including Di George) Yes Yes
Solid Tumours:
Hodgkins Disease
Other solid tumours

Yes
No

No
No
Acute Leukaemias:
Fludarabine (FLAG) containing regimens only

Yes


No

2 weeks prior to marrow or stem cell harvesting Yes Yes *
2 weeks prior to conditioning for both Allo-SCT and
A-SCT
Yes Yes *
Post Allo-SCT continue indefinitely Yes Yes *
Post A-SCT 3 months post ( 6 months post if TBI
given)
Yes Yes *
SCID or severe congenital immunodeficiency states Yes Yes

Allo-SCT=Allogeneic stem cell transplant
A-SCT=Autologous stem cell transplant
* for CMV requirements refer to individual patients transplant protocols



Blood Transfusion Version: 1.1 Page 4 of 7
Author: Dr B Gibson Authorised by: Schiehallion
group
Issue Date: September 2006
Date of Review: September 2008 Q-Pulse Ref: YOR-Haem-001

3. Indications for Transfusion
ANAEMIA - RED CELLS:
The transfusion threshold for red cell transfusion is Hb <8.0 g/dl except during
radiotherapy when it should be >10 g/dl.

Formula for calculating the volume of red cells to be transfused:
mls of packed cells = desired rise in Hb x weight in kg x 3.
or
approximately 10ml/kg.
Blood should be prescribed in mls and not in units and with a specified
rate.
If CMV negative or irradiated blood products are required this should be
clearly written on the prescription chart.
Patients should not be routinely transfused after 8pm except in
exceptional circumstances. Patients with a haemoglobin level below the
transfusion threshold who are asymptomatic should be transfused the
following day.

THROMBOCYTOPENIA PLATELETS:
The Transfusion Threshold for Platelet Transfusion is

10 x 10
9
/L in stable afebrile thrombocytopenic patients. Spontaneous
bleeding from mucus membranes (eg into gut, skin, renal tract, brain)
may occur when the platelet count falls below 10 x10
9
/L. If the platelet
count is greater than 10 x 10
9
/L then the decision to transfuse should be
based on the clinical situation. Active bleeding (eg rapidly appearing
multiple petechiae, epistaxis, macroscopic haematuria, GI bleeding), or
possible bleeding (eg severe headache, seizure activity, retinal
haemorrhage, evolving focal neurology) are indications for platelet
transfusion in thrombocytopenic children.
20 x 10
9
/L in patients with fever, sepsis or other causes of increased
platelet consumption without bleeding. Salicylates (eg aspirin) and other
non-steroidal anti-inflammatory drugs should not be used.
50 x 10
9
/L prior to invasive procedures (line removal/insertion)
50 x 10
9
/L in CNS tumours to prevent intracerebral or spinal bleeding in
those with residual tumour. A lower threshold (30 x 10
9
/L) may be
appropriate in patients with no residual disease, or in those who are more
than 4 months from surgery.

Volume of Platelets to be Transfused
Children <15 kg 15 mls/kg
Children >15 kg - Apheresis Unit

Ordering Platelets
If a patient requires platelets check with Blood Bank whether or not they
have platelets in stock.
If not, order the platelets from SNBTS at Gartnaval (tel: 357-7802). You
will be asked to provide the patients name, blood group and Rhesus
status, and any special requirements (CMV negative or irradiated). A HISS
request is required for all blood products, including platelets.
Blood Transfusion Version: 1.1 Page 5 of 7
Author: Dr B Gibson Authorised by: Schiehallion
group
Issue Date: September 2006
Date of Review: September 2008 Q-Pulse Ref: YOR-Haem-001

If it can be anticipated that a patient will require platelets (e.g. requiring
platelets prior to surgery the following day) these should be ordered so
that they are available at the time of surgery. It is important to tell SNBTS
when the platelets will be transfused to avoid a unit being dispatched
which will expire before use.
Ideally the platelet requirements for all of the patients on the ward should
be ordered from SNBTS as soon as the ward blood counts are available. It
is useful to check with the other team before ordering platelets to prevent
numerous calls and platelet deliveries.

ABNORMAL COAGULATION - FRESH FROZEN PLASMA (FFP):
FFP should not be used indiscriminately. It should only be used to correct
an abnormal coagulation screen and not used for volume replacement.
Children under the age of 16 yrs should receive viral inactivated
methylene blue FFP.
Volume of FFP to be transfused : 10-15 mls/kg.

LOW FIBRINOGEN CRYOPRECIPITATE:

Cryoprecipitate may be used to correct a low fibrinogen.
Children under the age of 16 yrs should receive viral inactivated
methylene blue cryoprecipitate.
Volume of cryoprecipitate to be transfused : 5-10 mls/kg.

ALBUMIN:

4% albumin contains 4g of albumin in 100ml.
20% albumin contains 20g of albumin in 100 ml.
The amount of albumin infused should be precisely calculated in grams to
raise the childs albumin to the required level.

Example:
A child weighing 25kg with a blood volume of 80 ml/kg has a total
blood volume of 2000ml (25x80=2000).
To increment the albumin by 5 g/l will require 10g albumin, which is
50ml 20% albumin.

Increment required X Weight X 8
% albumin solution used
= Volume albumin solution
required (ml)


4. Transfusion Reactions
FEBRILE REACTIONS:
Febrile reactions are common and may be due to leucocyte or platelet antibodies,
cytokines or occasionally plasma proteins. Leucocyte depletion of blood usually
prevents febrile reactions associated with red cell transfusion but not those
associated with platelet transfusion.

Fever will normally resolve if the infusion is stopped and paracetamol given.
Restarting the infusion at a slower rate may allow completion without further
reaction.
Blood Transfusion Version: 1.1 Page 6 of 7
Author: Dr B Gibson Authorised by: Schiehallion
group
Issue Date: September 2006
Date of Review: September 2008 Q-Pulse Ref: YOR-Haem-001


URTICARIAL REACTIONS:
Urticarial reactions are also common and do not normally lead to more severe
reactions. Urticaria will usually resolve with an antihistamine.

ANAPHYLAXIS:
Anaphylaxis is rare but more common with blood components that contain large
volumes of plasma such as FFP or platelets. Signs include hypotension,
bronchospasm, periorbital and larnygeal oedema, vomiting, dyspnoea and
urticaria. Anaphylaxis occurs when a patient, who is pre-sensitised to an allergen
producing IgE or IgG antibodies, is re-exposed to that particular antigen. Patients
with severe IgA deficiency can develop antibodies to IgA and develop anaphylaxis
if exposed to IgA by transfusion. Treatment is similar to that of any patient with
anaphylaxis. Patients with IgA antibodies who require further transfusion should
have blood components from IgA deficient donors or washed red cells.

TRANSFUSION OF A BACTERIALLY CONTAMINATED UNIT OF BLOOD OR PLATELETS:
Platelets are more commonly implicated than red cells, but the infusion of any
bacterially contaminated blood product is likely to result in the rapid onset of
hypotension, rigors and collapse. When bacterial contamination is suspected the
unit should be inspected for discolouration.

TRALI - TRANSFUSION-RELATED LUNG INJURY:
Transfusion- related lung injury (TRALI) is defined as acute dyspnoea with
hypoxia and bilateral pulmonary infiltrates occurring during or within the 24 hr
period after a transfusion with no other apparent cause. TRALI results from a
reaction of donor leucocyte antibodies with recipient white cell antigens. This can
be life-threatening and is often misdiagnosed as infection or fluid overload. It is
commoner with the transfusion of FFP or platelets than with red cells and the
donor is usually female. Since 2004 FFP has been prepared from male donations
only.

Immune Haemolysis:
Intravascular haemolysis in response to an ABO incompatible transfusion
is rapid and severe and is due to IgM anti-A and anti- B complement fixing
antibodies in the recipient. The patient may develop fever, flushing,
sweating, abdominal pain, hypotension and vomiting. DIC and acute
tubular necrosis may follow.
The severity of the reaction depends upon the titre of antibody present
and the associated mortality is high.
Extravascular haemolysis, most often due to anti -D, Kell, Duffy and Kidd
antigens, does not involve complement fixing antibodies. The transfused
cells become coated with IgG antibody and are removed from the
peripheral circulation over several hours. Occasionally, haemolysis may
be due to undetectable levels of pre-existing antibodies (again usually
anti-Kidd, D, Kell or Duffy), which are boosted by the transfusion and
cause increasing haemolysis over the subsequent 2 - 10 days post-
transfusion as antibody levels rise.
With rapid haemolysis the haemoglobin level falls dramatically and the
bilirubin level rises. Haemoglobin released from red cells saturates the
plasma haptoglobins and excess free haemoglobin is eliminated in the
urine. Renal tubular cells become loaded with haemosiderin and
haemosiderin appears in the urine. Free haemoglobin is also removed by
hepatic macrophages, releasing Fe(III)-containing haem groups, which
bind to plasma albumin producing methaemalbumin.
Blood Transfusion Version: 1.1 Page 7 of 7
Author: Dr B Gibson Authorised by: Schiehallion
group
Issue Date: September 2006
Date of Review: September 2008 Q-Pulse Ref: YOR-Haem-001


Management of a Suspected Severe Haemolytic Transfusion Reaction
1. Stop the transfusion

2. Resuscitate the patient
3. Investigate the cause of the reaction.
Check patient and blood product identity is correct
Inspect the bag for any signs of discolouration, which might
suggest bacterial contamination.
Inform laboratory, who will repeat the blood group and cross
match on pre-transfusion sample.
Send samples from patient and blood product for investigation of
suspected antibody.
Send blood cultures from both patient and blood product.
Check the patients FBC count, coagulation screen with D-dimers,
direct antiglobulin test, U&E and creatinine, bilirubin and free
haemoglobin immediately and after an interval of several hours.
Repeat at 24 hours or sooner if reaction is severe.
At 1 week, perform screen for red or white cell antibodies.

4. Notify Consultant Haematologist so that incident can be appropriately
investigated and reported to SHOT.