COLLEGE OF HEALTH – HAIL
Medical laboratory Dept.- Second term
THIRD YEAR – Blood banking
Compatibility test
PRACTICE -7
INVESTIGATION OF A TRANSFUSION REACTION
Adverse events related to transfusion can be acute (within 24 hours) or delayed (see
Table below ). Transfusion laboratories should immediately be informed of a suspected
transfusion reaction, being ideally placed to coordinate investigation, to communicate
with clinicians and transfusion services, and to advise about appropriate choice of blood
products for subsequent transfusions.
Acute transfusion reactions are easier to attribute to the transfusion than delayed
reactions, although, in patients who are already very ill, they can go undiagnosed. The
symptoms and signs of acute transfusion reactions are similar regardless of the cause;
treatment, and investigation of causes is simultaneous. It is easier to distinguish
between the causes of delayed transfusion reactions, but it may be more difficult to
recognise their relationship to the transfusion episode because of the delay in onset.
The following scheme outlines the role of the laboratory in investigation and
management of transfusion reactions, and a very useful algorithm can be found in the
Handbook of Transfusion Medicine.
Types of transfusion reaction
Acute transfusion reactions Delayed transfusion reactions
Acute haemolytic reaction Delayed haemolytic reaction
Anaphylaxis Transfusion transmitted infection
Bacterial contamination of blood product Transfusion-associated graft versus host disease
Transfusion-associated acute lung injury Posttransfusion purpura
Acute fluid overload Iron overload
Allergic reaction Immunosuppression
1
Acute transfusion reactions Delayed transfusion reactions
Febrile nonhaemolytic transfusion reaction —
Acute Transfusion Reactions
Acute life-threatening transfusion reactions can result from the following:
1. Acute intravascular haemolysis as a result of ABO incompatibility
2. Acute intravascular haemolysis can occur, although rarely as a result of other red
cell antibodies that activate complement through to the membrane attack complex
3. Severe extravascular haemolysis—this may happen where a strong antibody,
which does not bind complement or only binds it to the C3 stage, is missed in
pretransfusion testing and causes rapid extravascular clearance of incompatible
transfused red cells. These reactions are usually less severe than those caused
by ABO incompatibilities.
4. Anaphylaxis and severe acute allergic reactions—these are more commonly
associated with blood products containing large amounts of plasma where the
recipient has been presensitised to an allergen in the donor plasma. Recipients
with IgA deficiency can develop antibodies to IgA.
5. Transfusion of an infected blood product—this is more common with platelets
because they are stored at room temperature. If contamination is proven, the
blood centre must be informed so that other components from the same donor
can be traced.
6. Transfusion-associated acute lung injury is an acute respiratory disorder, with one
mechanism being passive transfer of antibodies in the donor unit that react with
the recipient's own white blood cells, resulting in noncardiogenic interstitial
pulmonary oedema.
Although rare, the onset of acute transfusion reactions is usually very dramatic and the
patient is acutely ill. Treatment is aimed at resuscitating the patient and elucidating the
cause to try and prevent any further incidents ( Table below ). In addition, there are
unpleasant but not life-threatening reactions that may occur during transfusion. They
include the following:
2
Allergic reactions—a mild urticaria or itching caused by a reaction to plasma proteins in
the donor unit
Immediate investigations in the case of an acute transfusion reaction
Check for haemolysis
Perform visual examination of patient's plasma and urine (plasma and urine
haemoglobin can be checked but this is not essential).
Blood film will show spherocytosis, red cell fragmentation.
Bilirubin and lactate dehydrogenase (LDH) levels will be raised.
Check for incompatibility
Check the documentation and the patient's identity.
Repeat ABO group of patient pretransfusion and posttransfusion and of the donor
unit(s).
Screen the patient for red cell antibodies pretransfusion and posttransfusion.
Repeat crossmatch with pretransfusion and posttransfusion samples.
Direct antiglobulin test (DAT) on patient.
Eluate from patient's red cells if DAT is positive.
Check for disseminated intravascular coagulation
Perform blood count and film, coagulation screen, and fibrin degradation products (or D-
dimers).
Check for renal function
Check blood urea, creatinine, and electrolytes.
Check for bacterial infections
Take blood cultures from the patient and donor unit including immediate gram stain.
Immunological investigations
Check immunoglobulin A (IgA) levels and anti-IgA antibodies.
Febrile non-haemolytic transfusion reactions—recipient's antibodies that react to
donor white cells and cause an increase in temperature of no more that 1°C;
alternatively, cytokines released from white cells in the donor units can cause a
similar reaction. These conditions usually settle on slowing the transfusion and
administration of antipyretics and antihistamines. They do not require detailed
investigation.
Acute Intravascular Haemolysis
3
Transfused red cells react with the patient's own anti-A or anti-B, and the red cells are
destroyed in the circulation, causing collapse, renal failure, and disseminated
intravascular coagulation. Transfusion of ABO-incompatible cells usually results from an
identification error. This can occur at point of blood sampling and labelling (wrong blood
in tube), laboratory testing (technical error), blood unit labelling (administrative error),
and collection from the blood refrigerator or inadequate bedside checking. If red cells
are mistakenly transfused to the wrong patient, there is approximately a 1 in 3 chance
that ABO incompatibility will occur. The reaction is most severe if group A blood is
transfused to a patient who is group O, and only a few millilitres of red cells are required
to cause this reaction. Prompt action in recognising this acute emergency and stopping
the transfusion may lead to a better outcome because the severity depends on the
volume of blood transfused. If an acute transfusion reaction is suspected, the laboratory
must be informed immediately and the unit of blood and giving set must be returned to
the laboratory with blood and urine samples from the patient ( Table 20.10 ).
Documentation Check
Patient identification, the compatibility form, and the compatibility label of the blood unit
should be checked again at the bedside. Any discrepancies must be notified to the
transfusion laboratory immediately. If the wrong blood has been administered, the units
intended for that patient must be withdrawn from issue to prevent another parallel error
occurring with another patient who may have the same or a similar name.
Serological Investigations
Serological investigations have a twofold purpose: (a) to check for any laboratory errors
in the pretransfusion sample group and compatibility check and (b) to repeat the group
and compatibility tests with the posttransfusion sample to see if the pretransfusion
sample was from the correct patient. Reactions in liquid-phase tests should be read
microscopically to detect any mixed-field reaction.
Tests for Haemolysis
Because not all acute transfusion reactions are the result of haemolysis, haematological
and biochemical tests as well as visual inspection of the plasma/serum and urine are
required (see Chapter 9 ). Further tests may be required to manage the resuscitation of
the patient and direct the use of blood products to treat disseminated intravascular
coagulation.
Microbiological Tests
If the cause of the acute transfusion reaction is still unclear, blood cultures should be
taken from the unit and the patient. Blood centres issue guidance for the investigation of
potentially contaminated units.
Delayed Haemolytic Transfusion Reaction
4
A delayed haemolytic transfusion reaction occurs when the recipient has been
immunised to a red cell antigen by a previous transfusion or during pregnancy but the
antibody is present at low or undetectable levels. A secondary immune response is
mounted to the incompatible antigen that has been transfused. The IgG- and/or
complement-coated red cells are destroyed in the spleen and liver. Kidd antibodies are
often implicated in delayed transfusion reactions because they are difficult to detect,
often displaying a dosage effect, fall rapidly to undetectable levels, and are frequently
present in combinations of antibodies.
Haematological Investigation
The following suggest a delayed haemolytic transfusion reaction:
Haemoglobin concentration falls more rapidly than would be expected after a red
cell transfusion
Increase in haemoglobin concentration is less than expected for the number of
units transfused
Blood film shows spherocytosis
Positive direct antiglobulin test
Unconjugated bilirubin raised
Serological Investigation
It is desirable to have the pretransfusion sample available to test in addition to a post-
transfusion sample, but this is not always possible because of the delay between the
time of the transfusion and the investigation. It has been recommended by some that
plasma/serum samples are saved on all patients who are transfused, but this is not
always practical. Unless the reaction is acute, the units transfused will not be available
for retesting. In the United Kingdom, the phenotype of each unit is provided by the
National Blood Service, and this information can help in the investigation of a delayed
transfusion reaction. The following tests should be carried out, preferably using different
or more sensitive techniques:
1. Confirm the ABO and D group of the patient on a pretransfusion and
posttransfusion sample.
2. Perform a direct antiglobulin test on the patient's pretransfusion and
posttransfusion washed red cells. In the event of a positive direct antiglobulin test,
elution of the antibody may aid identification or confirm specificities in cases of
non-ABO incompatibility.
3. Repeat the crossmatch, if possible, using pretransfusion and posttransfusion
samples.
4. Screen the pretransfusion and posttransfusion samples for red cell antibodies and
identify any antibodies. The immediate posttransfusion sample may have no
detectable red cell antibodies, al-though they may be eluted from the patient's red
cells if the direct antiglobulin test is positive. It is also possible to have a delayed
5
haemolytic transfusion reaction with a negative direct antiglobulin test because
the antibody-coated red cells have been removed from the circulation. If the
immediate posttransfusion investigation is inconclusive, repeat the tests 10 days
later to allow antibody levels to increase
6