Transfusion of
blood and blood products
The indications for transfusion in surgical
practice are as follows.
•
Following traumatic incidents where there has been severe blood loss, or
haemorrhage from pathological lesions, for example from the gastrointestinal
tract.
•
During major operative procedures where a certain amount of blood loss is
inevitable, for example abdominoperineal or cardiovascular surgery.
•
Following severe burns where, despite initial fluid and protein
replacement, there may be associated haemolysis.
•
Postoperatively in a patient who has become severely anaemic.
•
Preoperatively, usually in the form of packed cells given slowly (see
Blood fractions and Complications, later) in cases of chronic anaemia where
surgery is indicated urgently, i.e. where there is inadequate time for effective
iron or other replacement therapy, or where the anaemia is unresponsive to
therapy, for example aplastic anaemia.
•
To arrest haemorrhage or as a prophylactic measure prior to surgery, in a
patient with a haemorrhagic state such as thrombocytopenia, haemophilia or liver
disease (see Blood fractions, later).
Preparation of
blood products for transfusion
It is important that blood donors should be
fit and with no evidence of infection, in particular hepatitis and human
immunodeficiency virus (HIV) infection acquired immunodeficiency syndrome
(AIDS), which are transmitted in donor blood.
Blood
is collected into a sterile commercially prepared plastic bag with needle and
plastic tube attached in a complete, closed sterile unit.
With
the donor lying on a couch, a sphygmomanometer cuff is applied to the upper arm
and inflated to a pressure of 70 mmHg (9.3 kPa) or 80 mmHg (10.6 kPa). After
introducing 0.5 ml of local anaesthetic, a 15G needle is introduced into the
median cubital vein and 410 ml of blood allowed to run into the bag containing
75 ml of anticoagulant solution (CPD — citrate potassium dextrose).
During
collection, the blood is constantly mixed with the anticoagulant to prevent
clotting, and at the end of the procedure the tube is clamped and the needle
removed. Specimens for use in blood grouping and cross-matching procedures may
be obtained by clamping off small sections of the plastic tubing containing the
donor blood.
Blood storage
All blood for transfusion must be stored in
special blood bank refrigerators controlled at 40C ±
20C. Blood allowed to stand at higher temperatures for more
than 2 hours is in danger of transmitting infection.
CPD
blood has a shelf-life of 3 weeks (CPDA 1—5 weeks). The red blood cells, or
erythrocytes, suffer a temporary reduction (24—72 hours) in their ability to
release oxygen to the tissues of the recipient, so if a patient requires an
urgent and massive transfusion it is wise to give 1 or 2 units of blood which
are less than 7 days old.
White blood
cells
White blood cells are rapidly destroyed in
stored blood.
Platelets
At 40C the survival of platelets is
considerably reduced, and few are functionally useful after 24 hours. Platelets
which are separated (see Blood fractions below) show good survival even after 72
hours.
Clotting
factors
Like platelets, clotting factors VIII and V
are labile and their levels fall quickly.
Blood fractions
Whole blood may be divided into various
fractions. This is not only more economical of blood donors, but certain
fractions
are more appropriate than whole blood transfusion for certain clinical
conditions. Fractionation procedures are relatively safe and simple, using
sealed sterile plastic bag units.
Packed red
cells
Packed red cells are especially advisable in
patients with chronic anaemia, in the elderly, in small children and in patients
in whom introduction of large volumes of fluid may cause cardiac failure. Packed
red cells are suitable for most forms of transfusion therapy, including major
surgery, especially in association with clear fluids. Good packing can be
obtained by letting the blood sediment and removing the plasma, or by
centrifugation of whole blood at 2000—2300g for 15—20 minutes.
Platelet-rich
plasma
Platelet-rich plasma is suitable for
transfusions to patients with thrombocytopenia who are either bleeding or
require surgery. It is prepared by centrifugation of freshly donated blood at 15
0—200 g for 15—20 minutes.
Platelet
concentrate
Platelet concentrate for transfusion to
patients with thrombocytopenia is prepared by centrifugation of platelet rich
plasma at 1200—15 00 g for 15—20
minutes.
Plasma
This is removed after centrifugation of whole
blood at 2000—23 00 g for 15—20
minutes and it may be further processed or fractionated in various ways.
Human
albumin 4.5 per cent. Repeated fractionation of plasma by organic liquids
followed by heat treatment results in this plasma fraction, which is rich in
protein but free from the danger of transmission of serum hepatitis. This may be
stored for several months in liquid form at 40C and is suitable for
replacement of protein, for example following severe burns.
Fresh
frozen plasma. Plasma removed from fresh blood obtained within 4 hours is
rapidly frozen by immersing in a solid carbon dioxide and ethyl alcohol mixture.
This is stored at —400C and is a good source of all the coagulation
factors. It is the treatment of choice when considering surgery in patients with
abnormal coagulation due to severe liver failure. It may also be given in any of
the congenital clotting factor deficiency diseases in their milder forms,
especially Christmas disease (Factor
IX deficiency) or haemophilia (Factor VIII deficiency).
Cryoprecipitate.
When fresh frozen plasma is allowed to thaw at 40C a white glutinous
precipitate remains and, if the supernatant plasma is removed, this
cryoprecipitate is a very rich source of Factor VIII. It is stored at —400C
and is immediately available for treatment of patients with haemophilia
(Factor VIII deficiency). The advantage of cryoprecipitate treatment in
haemophilia is the simplicity of administering large quantities of Factor VIII
in relatively small volumes by intravenous injection. It is also a rich source
of fibrinogen, of value in hypofibrinogenaemic states.
Factor
VIII concentrate and Factor IX concentrate. Factor VIII concentrate and Factor
IX concentrate are stored in freeze-dried form.
Fibrinogen.
Fibrinogen is prepared by organic liquid fractionation of plasma and stored in
the dried form. When reconstituted with distilled water, it is used in patients
with severe depletion of fibrinogen (e.g. disseminated neurovascular coagulation or congenital afibrinogenaemia). It does, however, carry a high risk
of hepatitis.
SAG-mannitol
blood. Because of the need for blood products, there will be an increasing use
of SAG-M blood. A proportion of blood donations will have all the plasma
removed, which will be replaced with 100 ml of a crystalloid solution
containing: sodium chloride (877 mg), adenine (16.9 mg), glucose anhydrous (181
mg) and mannitol (525
mg).
This
allows good viability of the cells, but there is practically no protein
(albumin) present. For top-up transfusions for anaemia, this will not constitute
a problem.
For
healthy adults, the plasma albumin level will not be compromised by a
replacement transfusion of up to 4 units of SAG-M blood, after which whole blood
should be used. If this is not available, more SAG-M blood may be given,
supplemented by 1 unit (400 ml) of 4.5 per cent human albumin solution BP for
every 2 units of SAG-M blood. After 8 units of SAG-M red cells have been
transfused, the need for fresh frozen plasma and platelets should be considered,
after first checking the coagulation status and platelet count.
Blood grouping
and cross-matching
Human red cells have on the cell surface many
different antigens. For practical purposes, there are two groups of antigens
which are of major importance in surgical practice:
antigens of the ABO blood groups and antigens
of the rhesus (Rh) blood groups.
Antigens of the
ABO blood groups
These are strongly antigenic and are
associated with naturally occurring antibodies in the serum. Individuals show
four different ABO cell groups, as shown in Table
4.2.
Antigens of the
rhesus blood groups
The antigen of major importance in this group
is Rh(D), which is strongly antigenic and is present in approximately 85 per
cent of the population in the UK. Antibodies to the D antigen are not naturally
present in the serum of the remaining 15 per cent of individuals, but their
formation may be stimulated by the transfusion of Rh-positive red cells. Such
acquired antibodies are capable, during pregnancy, of crossing the placenta and,
if present in a Rh-negative mother, may cause severe haemolytic anaemia and even
death (hydrops fetalis) in a Rh-positive fetus in utero. The other minor blood group antigens may be associated
with naturally occurring antibodies, or may stimulate the formation of
antibodies on relatively rare occasions.
Incompatibility
If antibodies present in the recipient’s
serum are incompatible with the donor’s cells, a transfusion reaction will
result. This is the result of agglutination and haemolysis of the donated cells
leading in severe cases to acute renal tubular necrosis and renal failure. For
this reason, therefore, it is essential that all transfusion should be preceded
by:
• ABO and rhesus grouping of the recipient’s and donor’s cells so that only
ABO and Rh(D) compatible blood is given;
•
direct matching of the recipient’s serum with the donor’s cells to
confirm ABO compatibility and to test for rhesus and any other blood group
antibody present in the serum of the recipient.
Blood
grouping and cross-matching require full laboratory procedures and take 1 hour.
In emergencies it may be necessary to reduce this time, but the risk of doing
this must be weighed against the danger to the patient by the delay in
transfusion entailed by the full procedures. In such emergencies, it may be
advisable to restore the patient’s blood volume by saline, gelatin (e.g.
Haemaccel), dextran or human albumin 4.5 per cent until blood has been made
available. Alternatively, donor blood, group 0-negative, which is compatible
with the majority of individuals, should be given and this should always be
available in acute emergency situations.
Giving blood
Blood transfusion is commenced by:
•
careful checking of the donor blood: this should bear a compatibility
label stating the patient’s name, hospital reference number, ward and blood
group;
•
insertion of the needle or cannula — the latter may be valuable if
intravenous therapy is required for any length of time;
•
giving detailed written instructions as to the rate of flow, for example
40 drops/mm allows one 540 ml unit of blood to be transfused in 4 hours.
In
acute emergencies, it may be necessary to increase the rate of flow and it is
possible to give 1—2 units in 30 minutes using a pressure cuff around a
plastic bag of blood.
Warming
blood. During cardiopulmonary operations, the blood must be warmed before
reaching the patient by passing it through a carefully temperature-regulated
blood warming unit, thus reducing the risk of cardiac arrest from large volumes
of cold blood direct from the refrigerator.
Filtering
blood. A filter (Pall) with an absolute filtration rating of 40 micron will filter
off platelet aggregates and leucocytes membranes in stored blood.
Autotrans
fusion
This is an old, well-tried method of
immediately restoring a patient’s blood volume, by transfusion with his or her
own blood. In an emergency, for example, in a case of ruptured ectopic
gestation, the blood is collected from the peritoneal cavity and put into a
sterile container suitable for connecting to transfusion tubing. The classical
method of filtration of this blood to prevent the transfusion of any small clots
is to place a piece of sterile gauze within the container. Nowadays, special
autotransfusion apparatus is being marketed. For major elective procedures, the
patient may ‘donate’ his or her own blood, withdrawal and storage taking
place up to 3 weeks before it is required. Natural blood volume and most of the
red cell recovery will have taken place in that time.
Complications
of blood transfusion
Congestive
cardiac failure
This is especially liable to occur in the
elderly or where there is cardiovascular insufficiency, and may result from too
rapid infusion of large volumes of blood. It is advisable in the individual with
chronic anaemia to give packed red cells and, at the same time, give diuretic
drugs. The transfusion should be given slowly, i.e. I unit over 4—6 hours and,
if necessary, on two separate occasions.
‘Transfusion
reactions
These may be the result of the following
problems:
• Incompatibility. This should be avoided if the correct procedures of
grouping and cross-matching have been adopted but, in fact, it is nearly always
due to human error in the collection, labelling or checking of the specimens and
donor bags. The patient develops a rigor, temperature and pain in the loins, and
may become extremely alarmed. The transfusion should be stopped immediately, and
a fresh specimen of venous blood and urine from the patient sent together with
the residue of all the used units of
donor blood to the laboratory for checking.
A
close watch should be kept on the patient’s pulse, blood pressure and urinary
output. Frusemide 80—120 mg i.v. should be given to provoke a diuresis, and
repeated if the urine output falls below 30 ml/hour. Dialysis may be necessary.
• Simple pyrexial reactions in which the patient develops pyrexia, rigor and some
increase in pulse rate. These are the result of ‘pyrogens’ in the donor
apparatus and are largely avoided by the use of plastic disposable giving sets.
• Allergic reactions in which the patient develops mild tachycardia and
an urticarial rash; rarely an acute anaphylactic reaction may occur. This is the
result of allergic reaction to
• Sensitisation to leucocytes and
platelets. This
is not uncommon in those patients who have received many transfusions in the
past, for example for thalassaemia, refractory anaemia or aplastic anaemia. The
individual develops antibodies to donated white cells or platelets, which cause
reactions with each transfusion. They may be minimised by giving packed red
cells from which plasma and ‘huffy coat layers’ have been removed or by
‘washing’ of donor cells. Aspirin, antihistamines or steroids may also be
given to the recipient if necessary.
• Immunological
sensitisation. Only
the ABO, Kell and Rh(D) groups are considered for blood transfusion. Immune
antibodies may be stimulated by transfusion, and may give rise to difficulties
with compatibility tests or to haemolytic transfusion reactions.
Infections
There are four main reasons for blood
transfusion causing infection in the recipient.
• Serum hepatitis virus may
be transmitted from the donor and is usually a severe hepatitis arising
approximately 3 months after the transfusion. It should be avoided by adequate
verbal screening of the blood donor and by testing for the presence of the
hepatitis associated antigen in the blood prior to transfusion.
• HIV infection can be transmitted by blood and blood products. All donors must be
screened (see AIDS in Chapter 7). Haemophiliacs are at special risk because of
their more frequent requirements for blood products.
• Bacterial infection may result faulty storage. This arises most commonly
from the donor blood being left in a warm room for some hours before the
transfusion is commenced. This allows proliferation of any bacteria, and
transfusion of such infected blood may result in severe septicaemia in the
recipient and rapid death.
• Malaria can be transmitted by blood transfusion in areas where the disease is
endemic. Whenever possible, donors should be screened and the disease eradicated
(by treatment of the donors who are positive) before blood is obtained or
given. If the need for transfused blood is so urgent that precautions are
impossible before transfusion, then the patient should be given prophylactic
antimalarial drugs.
Thrombo
phlebitis
For more on thrombophlebitis see Chapter 16 of
this book.
Air embolism
For more on air embolism see Chapter 15 of
this book.
Coagulation
failure
Coagulation failure is due to:
• dilution of clotting factors/platelets due
to large volumes of stored blood being used to replace losses as stored blood is
low in platelets, Factor VIII and Factor V;
• disseminated intravascular coagulation (DIC) following an incompatible blood transfusion, particularly ABO
incompatibility. The further haemorrhage may be treated by replacement of the
deficient factors (usually fibrinogen, Factors VIII, V and II, and platelets),
with fresh frozen plasma, cryoprecipitate and platelet concentrates.
Paradoxically, heparin may be used sometimes for the treatment of DIC.
Haemophilia and
the congenital haemorrhagic diseases
Haemophilia
Haemophilia (haemophilia A) is a haemorrhagic
diathesis caused by the congenital deficiency in the blood of Factor VIII [antihaemophilic
globulin (AHG)]. It is a sex-linked characteristic, transmitted by the
asymptomatic female carriers, and manifest only in males.
The
levels of Factor VIII in the blood of severe haemophiliacs may be less than 1
percent of the average normal level. In the case of spontaneous haemorrhage
(e.g. into joints) treatment should aim at raising the level to at least 20 per
cent. Should surgery be anticipated in the haemophiliac, the level should be
raised to 50—100 per cent.
Factor
VIII concentrates are superseding cryoprecipitates. The amount of either
preparation depends on the problem and the level required for haemostasis, i.e.
more for surgery than for a haemarthrosis. Frequent monitoring of the Factor
VIII level will be necessary in cases involving surgery.
Additional
forms of therapy may include fresh blood, if necessary for blood loss, fresh
frozen plasma or, more rarely, dried concentrates of animal AHG (see also AIDS).
Christmas
disease
Christmas disease (haemophilia B) is a
congenital disease resulting from the deficiency of Factor IX (Christmas
factor). Clinically, the manifestations of the disease are similar to
haemophilia. Factor IX is replaced by the transfusion of fresh frozen plasma, or
by reconstituted dried concentrates of human Factor IX.
Haemophilic
joints
In both haemophilia and Christmas disease,
haemorrhage into joints is very common, and persistent and recurrent
haemarthrosis may result in permanent damage to the articular surfaces and
disorganisation of the joint. The most important feature of treatment is that it
should be prompt. Replacement of the clotting factor should be instituted
immediately and before severe tension is allowed to build up in the joint.
Von
Willebrand’s disease
Von Willebrand’s disease, with episodic
bleeding manifestations, is a type of haemorrhagic disease, with low plasma
levels of both Factor VIII complement and Factor VIII related antigen, and
platelet abnormalities.
Sickle-cell
disorders
Sickle-cell disorders can be a serious problem
in surgery, especially with children. All patients of the negroid ethnic type
should be screened for the presence of sickle haemoglobin. In sickle-cell
trait (HbA +
5) care to avoid hypoxia during anaesthesia is important. In sickle-cell anaemia, a preoperative partial exchange transfusion of
packed cells to reduce the haemoglobin S level to less than 30 percent may be
required, depending on the procedure and the length of the operation. Oxygen is
given for the prevention of hypoxia; hypothermia and dehydration must be
strenuously avoided. Spinal anaesthesia and tourniquets are contraindicated.
Pigments gallstone formation is common.
Blood
substitutes —
albumin, dextran, gelatin
One of the most urgent requirements in a
patient suffering from acute blood loss is the re-establishment of a normal
blood volume. This may be achieved satisfactorily with a number of plasma
substitutes.
Human albumin 4.5 per cent has superseded the use of dried plasma and can be
used whilst cross-matching is being performed. Two to three units (1.2 litres)
are given intravenously over 30 minutes. It is valuable in patients with burns
where there has been severe loss of protein. There is no risk of transmitting
hepatitis.
Dextrans are polysaccharide polymers of varying molecular weight producing an
osmotic pressure similar to that of plasma. They have the disadvantage of
inducing rouleaux of the red cells and this interferes with blood-grouping and
cross-matching procedures, hence the need for a blood sample beforehand.
Dextrans interfere with platelet function and may be associated with abnormal
bleeding, and for this reason it is recommended that the total volume of dextran
should not exceed 1000 ml.
Low-molecular-weight dext ran (40 000) (dextran 40, Rheomacrodex) has an immediate
effect in a restoring plasma volume, but it is transitory because the small
molecules are readily excreted by the kidney. It may be useful in preventing
sludging of red cells in small blood vessels, for example of the kidney, and
thus preventing the renal shutdown associated with severe hypotension. It is
less likely to induce rouleaux formation than the high-molecular-weight
compounds.
The
high-molecular-weight dextrans (110 000 and 70 000) (dextran 110 and
dextran 70) are less effective in the early phase of hypovolaemia but are longer
acting as they are retained for some time within the circulation.
Gelatin in a degraded form (molecular weight around