Transfusion reactions

Fever with or without chills Blood-transmissible diseases

Chills with or without slight rise in temperature Graft Versus Host Disease (GVHD)
Allergy Post-transfusion purpura (PTP)
Acute haemolytic transfusion reactions (HTR) Transfusion related lung injury (TRALI)
Delayed HTR Other transfusion reactions

Fever with or without chills

This is the most frequent transfusion reaction.

Cause
This reaction is chiefly the result of leukocyte antibodies. Such a reaction is unpleasant but temporary.
These antibodies are formed as a result of pregnancy or previous blood transfusions.
Fever during or shortly after transfusion can also be caused by haemolysis of erythrocytes by (irregular)
antibodies against erythrocytes (see 10.4) or through bacterial contamination of the blood product that
can be an immediate cause of sepsis. These reactions can have a serious clinical course and demand
direct intervention (11.1.2). It is for this reason that these causes must also be excluded.
Fever reactions can also occur with the administration of thrombocytes as a result of antibodies against
thrombocytes (HLA or thrombocyte-specific) or cytokines in the product

Action
• (particularly with temperature increases of 20 oC) detach the blood product as rapidly as
possible, leave the infusion needle in situ, and attach a clean infusion system filled with
physiological saline;
• check to see if it was the blood products selected for the patient that are/were actually
administered;
• extract blood from the patient for a repeat of the compatibility study (with erythrocyte transfusions)
and blood culture;
• submit all blood products that were administered before or during the transfusion for blood culture
and a repeat of the compatibility study (with erythrocyte transfusion). Likewise repeat the
compatibility study with the erythrocyte products that have not yet been administered.
• if necessary, investigate the blood of the patient for HLA antibodies.

Future policy
If the fever reaction occurs repeatedly and investigation of irregular antibodies against erythrocytes and
bacterial contamination are negative, it is recommended that premedication be used prior to the
transfusion. The administration of selected HLA-compatible thrombocytes is indicated (see also Chapter
4) for patients that had no further increase in the number of thrombocytes after thrombocyte transfusion in
the absence of other thrombocyte metabolism-promoting factors.
NB: Fever reactions should occur less frequently due to the introduction of leukocyte removal for all
cellular blood products.

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Chills with or without slight rise in temperature

Cause
Chills occurring with the administration of thrombocyte concentrates can be caused by cytokines that are
released from leukocytes in the thrombocyte product during storage. As from 1 September 2001, Sanquin
has removed the leukocytes from thrombocyte concentrates before storage. See also 10.1.

Action
Administer antihistamines and/or corticosteroids (dependent upon the local policy), and continue the
transfusion under clinical guidance (with slower infusion, if necessary).

Future policy
If the chills occur repeatedly, and the introduced investigations have disclosed nothing of importance,
then consideration may be given to premedication. Fewer reactions have been described with
thrombocytes in storage fluids than with thrombocytes in plasma.

Allergy: itching, urticaria, glottal oedema, anaphylactic shock

Cause
These reactions are chiefly the consequence of antibodies in the patient against plasma proteins from the
donor, or the presence of atopes in the blood products.

Action
With itching and/or urticaria: in general, this is no reason for interrupting the transfusion. Antihistamines
may be considered. The transfusion rate can be reduced, if necessary.
Glottal oedema and/or anaphylactic shock: immediately end the transfusion. Administration of
antihistamines, corticosteroids and/or adrenaline, shock control. Examination: the patient’s IgA and anti-
IgA.

Future policy
With anti-IgA: washed erythrocytes; it is preferable that no plasma-containing blood products be
administered. In special cases and in consultation with the blood bank, consideration can be given to the
calling up of IgA negative donors. Rule out other causes with anaphylactic shock without anti-IgA: test
transfusion under intensive supervision.
For remaining cases: if the reaction is repeated with washed erythrocytes, consideration can be given to
administering antihistamines prior to transfusion.

Acute haemolytic transfusion reactions (HTR)

Cause
These reactions are the result of (irregular) antibodies from the patient directed against donor
erythrocytes with the corresponding antigen. The cause is usually a human error in the organisation, such
as a switching of cross-match tubes, an incorrect label on the cross-match tube, an incorrect label on the
blood bag, and the switching of patients or blood products.
With ABO incompatibility, an intravascular haemolysis (which lasts a few hours) can already occur within
a few minutes. With irregular antibodies against erythrocytes, the reaction begins only after a few hours
and can last for days.
Symptoms: warm feeling at the infusion site and in the face, cold chills, agitation, high fever, chest pain,
back pain, dyspnea, nausea, tachycardia, hypotension, tendencies towards bleeding as a result of
disseminated intravascular coagulation, icterus and reduced kidney function with oliguria/anuria.

Action
• Immediately halt the transfusion, leave the infusion needle in situ and attach physiological saline.
Check heart rate, blood pressure and temperature.
• Hypotension must be counteracted and the kidney circulation guaranteed. Fluid administration, if
necessary supplemented with 20% Mannitol and/or intravenous furosemide, must be directed
towards obtaining a urine production of a minimum of 1 – 2 mL/kg/hour. Alkalinisation of the urine
(by means of sodium-bicarbonate administration to the patient) should be considered. If
necessary, treatment of coagulation disorders and hyperpyrexia.
• Check to see if it was the blood products selected for the patient that are/were actually
administered. Check the entire administration line!
• Submit all blood product bags that were administered before or during the transfusion reaction to
the blood transfusion laboratory.
 • Patients’ blood from before and after transfusion must be investigated for antibodies (direct anti-
globulin test) and ABO blood group/Rhesus (D) factor, while screening for irregular antibodies
and matching tests must be repeated (from out of the matching tube as well as from out of the
blood bag[s]).
• Likewise repeat the compatibility study with the erythrocyte products that have not yet been
administered.
• Bacterial cultivation of donor blood and patient blood must also be instigated.
• Other laboratory investigations: haemoglobin, LDH, bilirubin, haptoglobin, thrombocytes,
haemostasis assays, fibrinogen, fibrinogen degradation products, creatinine, and free
haemoglobin in serum and urine.

Future policy
(Typed) compatible erythrocytes.
A life-long record of information about the presence of antibodies against erythrocytes (attached to the
patients’ data) must be kept in the blood transfusion laboratory on a blood groups card (with explanation
to the patient) and/or on a Medical Alert Bracelet.

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Delayed HTR
This reaction is the consequence of the rapid formation of irregular antibodies against erythrocytes. The
antibody production proceeds so rapidly that a reduction of the HB concentration occurs, or the expected
Hb increase fails to appear, 2 to 10 days afterwards There may also be the occurrence of icterus, fever
and, occasionally, haemoglobinuria.

Cause
The patient was immunised with a previous pregnancy or transfusion, but these antibodies are not
demonstrable at the moment of the compatibility study. The new erythrocyte transfusion acts as a booster
injection with secondary immune response and the production of a large titre of antibodies that result in
the breakdown of erythrocytes.

Action
Check the administrative procedure of the most recent transfusion (identification of patient and donor,
transfusion history of the patient, T/S report and or matching test, etc.). The patient’s blood is investigated
as rapidly as possible after transfusion for antibodies against erythrocytes (direct anti-globulin test,
screening against panel test erythrocytes).
Other clinical investigation: LDH, bilirubin, haptoglobin, and free haemoglobin in serum and urine.

Future policy
(Typed) compatible erythrocytes.
A life-long record of information about the presence of antibodies against erythrocytes (attached to the
patients’ data) must be kept in the blood transfusion laboratory on a blood groups card (with explanation
to the patient) and/or on a Medical Alert Bracelet.

Blood-transmissible diseases
The transfer of viral infections such as HIV and hepatitis currently occurs only rarely. The risk of
transmission of the hepatitis B virus in tested blood is estimated at one in 200,000 transfusions, while that
of HIV and hepatitis C virus are approximately one in 1 to 2 million transfusions. Bacterial contamination
of donor blood can lead in a few cases to the induction of bacteraemia or sepsis. Other blood-
transmissible infections such as malaria, toxoplasmosis, babesiosis and Chagas’ disease occur only
extremely rarely, or not at all, in the Netherlands. If the recipient of a transfusion/transfusions experiences
a blood-transmissible disease, then the Sanquin blood bank (alongside the hospital blood transfusion
laboratory) must be notified of this as quickly as possible (including time[s] of transfusions[s] with reports
of UIN and product code[s]). Blood products that are from the donor(s) and that are still in storage can be
blocked so that transfusions to other patients can still be prevented.
Cytomegalovirus (CMV) infection is a persistent infection that occurs in 50-60% of the Dutch population.
The virus is latently present in the leukocytes, as a result of which transfer of CMV can occur via
leukocyte-containing cellular blood products. CMV-safe blood products are therefore indicated for anti-
CMV-negative patients with reduced immunity. CMV-safe cellular blood products include: leukocyte-free
blood products or blood products from tested anti-CMV negative donors. As from 1 January 2002, all
standard cellular blood products from Sanquin are leukocyte-free.
Antenatal CMV infection can lead to serious symptoms of illness, including intra-uterine growth
retardation and microcephalia. Intra-uterine transfusions are tested for CMV.

Graft Versus Host Disease (GVHD)

GVHD can be prevented by radiating cellular blood products upon indication (see 8.3) with at least 25 Gy.
See the product description for radiated blood products.

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Post-transfusion purpura (PTP)

Post-transfusion purpura (PTP) is a temporary, acute and serious thrombocytopoenia that may arise 5 –
12 days after transfusion, chiefly as the consequence of anti-HPA1a (anti-thrombocytes) antibodies in the
recipient. PTP occurs mostly in older, HPA-1a negative women that were earlier immunised by
pregnancies or transfusions. PTP also occurs sporadically in men. The tendency towards haemorrhage
manifests itself as extensive purpura, but there may also be the occurrence of gastro-intestinal
haemorrhages or haemorrhages in the urinary tract. The mechanism of the breakdown of the patient’s
own (HPA-1a negative) thrombocytes is not clear. Treatment consists of the prevention of serious
haemorrhages. High doses of intravenous immunoglobulin (IVIG) and/or corticosteroids are sometimes
effective. Thrombocytes, even HPA typed, frequently have no effect. The administration of plasma must
be avoided because this frequently contains dissolvable thrombocyte antigens.

Transfusion related lung injury (TRALI)

TRALI involves an acutely arising elevated permeability of the pulmonary microcirculation with massive
leakage of fluid and protein in the alveolus and the interstitium, mostly within 6 hours after transfusion.
The occurrence of TRALI is in many cases associated with anti-granulocyte or anti-HLA antibodies in the
donor, and sometimes in the recipient. The precise mechanism is not known. Treatment consists of
aggressive respiration therapy.

Other transfusion reactions

Allo-immunisation: Allo-immunisation against erythrocytes can arise through transfusions and

pregnancies. It can cause problems with future erythrocyte transfusions and pregnancies (haemolytic
illness of the newborn); see 3.1.4. Allo-immunisation against HLA antigens can arise through transfusions
and pregnancies and be the provocation of refractoriness with future thrombocyte transfusions. Allo-
immunisation against HPA antigen can arise due to transfusions and pregnancies and can be the
provocation of post transfusion purpura with future transfusions and neonatal allo-immune
thrombocytopoenia with future pregnancies.

Circulatory overfilling leading to pulmonary oedema can occur after transfusion of an excessive volume
or an excessive speed of transfusion. This is chiefly a risk for the elderly and patients with serious chronic
anaemia for which a low erythrocyte volume is compensated by a high plasma volume. Small
concentrations of transfused product can elicit symptoms in patients that are actually already at risk and
have a positive fluid balance.

Under cooling can be a risk for cardiac arrhythmia or provoke cardiac arrest. Rapid transfusion of a large
concentration of blood can cause the body temperature to drop. The risk is particularly large in patients in
shock or those who have undergone a surgical procedure under anaesthesia that is already able to
influence the temperature regulation. A blood warmer may be considered with rapid transfusions. In order
to prevent the occurrence of haemolysis, only blood warmers that were intended for this should be used.

Citrate toxicity is caused by a reduction of ionised calcium through the presence of a large concentration
of citrate anticoagulants in the circulation.
Hypocalcaemia; the stock of calcium in the body is large, citrate is mostly immediately metabolised by
the liver, and furthermore, this complication is rare. Patients with serious hepatic disease or with shock
resulting in limitation of the hepatic circulation can develop physiologically significant hypocalcaemia after
rapid transfusions of large concentrations of blood products (in particular, plasma). It is recommended
that there be an assay of ionised calcium and monitoring with an electrocardiogram.

Other metabolic changes can arise with rapid transfusion or transfusion of large concentrations (chiefly
in patients with already existing circulatory or metabolic problems). This includes, among others, acidosis
or alkalosis (caused by the conversion of citrate to citric acid, and the subsequent conversion into
pyruvate and bicarbonate) and hyperkalaemia or hypokalaemia.

For small children with massive blood loss, people should be prepared for a high to very high potassium
in the supernatant if the erythrocytes have been stored longer (5 to 35 days). This potassium can lead to
rhythm disorders and cardiac arrest with rapid transfusions of large concentrations.

Nonimmunologic haemolysis rarely occurs, but can be provoked by intravenous administration of

hypotonic fluids, simultaneous administration of medicines or parenteral feeding, bacterial toxins,
physiologic damage of erythrocytes through freezing or heating, metabolic damage with
haemoglobinopathy, or enzyme deficiencies.

ALWAYS REPORT TRANSFUSION REACTIONS TO THE TRANSFUSION LABORATORY OF YOUR

HOSPITAL

ALL TRANSFUSION REACTIONS THAT MAY BE RELATED TO THE BLOOD PRODUCT MUST BE
REPORTED AS RAPIDLY AS POSSIBLE TO THE SANQUIN BLOOD BLANK.

Haemovigilance
In 2003 the national Foundation for Transfusion Reactions in Patients (TRIP) will take over the national
registration and reporting of complications and undesirable effects of blood transfusions.

7 ADVERSE REACTIONS TO
TRANSFUSION
Any adverse reaction to the transfusion of blood or blood components should be reported
to Blood Bank personnel as soon as possible.
Speed is essential in such situations because of the possible life-threatening nature of
acute transfusion reactions. The evaluation of all adverse reactions to transfusion is the
responsibility of the medical staff of the Blood Bank and the notification of such a
reaction by the patient unit serves as a request for Blood Bank physician consultation.
The Blood Bank is required to report any death resulting from transfusion to the Food
and Drug Administration.
Reactions may be separated into reactions that present in proximity to the transfusion and
those that present at some time subsequent to the transfusion. Suspected post-transfusion
disease, which may present at a considerable time following transfusion, must also be
reported to the Blood Bank. Investigation of these reports may result in identification of
"carrier" donors who are removed from the donor pool
 A Blood Bank physician should be consulted regarding the evaluation of patients with
reactions, as well as selection of appropriate blood components for future transfusion.
In the case of a mild urticarial and febrile reactions, with no other signs or symptoms
attributable to blood transfusion, it may be possible to reinitiate the blood transfusion
Such a decision must be arrived at through consultation between the physician reporting
the reaction and a Blood Bank physician
Premedication for Recipients of Granulocytes
It is suggested that patients receiving granulocytes who have a history of febrile reactions
to blood components be pretreated with antipyretic agents if there are no
contraindications to the use of these drugs. See Febrile Transfusion Reactions. In general,
transfusion of Granulocytes should be terminated only for such complications as severe
flank pain, chest pain, hemoglobinemia and hemoglobinuria, hypotension, laryngospasm,
or acute pulmonary injury.

Reaction Type Symptoms Cause Frequency Preven

Acute Hemolytic Fever, chills and fever, the Human error such as Rare proper
Reaction feeling of heat along the vein mislabeled of patie
in which the blood is being pretransfusion pretrans
transfused, pain in the lumbar specimen; the samples
region, constricting pain in the transfusion of properly compon
chest, tachycardia, hypo- labeled blood to the time of
tension, and hemoglobinemia wrong person, or
with subsequent hemoglo- clerical errors occurring
binuria and hyperbilirubin- within the Blood Bank
emia. transfused red cells react
A "feeling of impending with circulating
doom" is frequently reported antibody in the recipient
by the patient as an early sign with resultant
of this reaction. intravascular hemolysis

In an unconscious or anesthe-
tized patient: Uncontrollable
bleeding due to disseminated
intravascular coagulation may
be the only sign of a
hemolytic transfusion reaction
Most likely to occur
when a group O patient
is mistakenly transfused
with group A, B, or AB
blood. Patients
receiving a major ABO-
incompatible marrow or
stem cell transplant with
sufficient red cell
content will likely
develop an acute

DELAYED the most common signs are a
HEMOLYTIC falling hematocrit (due to
REACTIONDelayed extravascular destruction of
Hemolytic Reaction the transfused red blood cells)
and a positive direct
antiglobulin (Coombs) test
(DAT).
"delayed" hemolytic reactions
commonly occurs about 4-8
days after blood transfusion,
but may develop up to one
Notify the Blood month later. There may also
Bank at the time the be hemoglobinuria and a mild
reaction is suspected, elevation of the serum
to allow prompt bilirubin. . Symptomatic
investigation. Care patients may manifest fever
must be taken that and leukocytosis thus
subsequently appearing to have an occult
transfused red cells infection.
lack the antigen
corresponding to the
patient's antibody.
Febrile fever or chill fever A
temperature rise of 1.8 F or
1.0 C from the baseline
Allergic - urticaria allergic reactions may be
associated with laryngeal
edema and bronchospasm.
If coupled with another sign,
such as fever, evaluation for a
hemolytic reaction may be
indicated.
Allergic - anaphylactic or anaphylactoid
Anaphylaxis Respiratory involvement with
dyspnea or stridor may be
hemolytic reaction
Many delayed Uncomon
hemolytic reactions will
go undetected because
the red cell destruction
occurs slowly
Delayed hemolytic
reactions occur in
patients who have
developed antibodies
from previous
transfusion or
pregnancy but, at the
time of pretransfusion
testing, the antibody in
question is too weak to
be detected by standard
procedures. Subsequent
transfusion with red
cells having the
corresponding antigen
results in an anamnestic
antibody response and
hemolysis of transfused
red cells.
Cytokines and 1 in 8
antibodies to leukocyte transfusions
antigens reacting with
leukocytes or leukocyte
fragments
this reaction is caused 1% of recipients
by foreign plasma
proteins
may be due to anti-IgA Rare
 more pronounced than is
usually seen in typical allergic
reactions.
Reactions manifest
cardiovascular instability that
includes hypotension,
tachycardia, loss of
consciousness, cardiac
arrhythmia, shock and cardiac
arrest.

TRALI abrupt onset of TRALI has been TRALI is a rare Most ca

noncardiogenic pulmonary associated with the though under resolve
edema Severe cases may presence of antibodies recognized hours a
require assisted ventilation in the donor plasma complication of fatalitie
with high FIO2.. reactive to recipient transfusion approxi
leukocyte antigens or percent
with the production of
inflammatory mediators
during storage of
cellular blood
components

Volume Overlead transfusion-related Infuse s

volume overload volume

Bacterial hypotension, shock, fever and
Contamination chills, nausea and vomiting,
and respiratory distress.
Diagnosis is established by
Gram stain and blood culture
of both the blood component
and the recipient.distress
Bacterial contamination rare but difficult
occurs when a small to detect prior to
number of bacteria enter transfusion
a blood component Autologous blood
during collection or may be
processing.. During contaminated
storage, bacteria may with bacteria,
proliferate, resulting in a particularly if the
large number of patient had an
organisms, and possible active infection at
endotoxin, being given the time of
with the transfusion donation.

Hypotension A drop of at least 10 mm Hg Some reactions have

in systolic or diastolic arterial been associated with
blood pressure in the absence angiotensin converting
of signs or symptoms of other enzyme (ACE) inhibitor
 transfusion reactions drugs or the use of
if the immediate leukocyte reduction
pretransfusion blood pressure filters.
is elevated from the patient’s Hypotensive reactions
typical blood pressure, and the have been associated
arterial pressure does not fall with red cell and platelet
below the patient’s usual transfusions.
blood pressure, it should not
be considered a hypotensive
reaction. The onset of
hypotension is during the
transfusion, and resolves
quickly with discontinuation
of the transfusion.
If hypotension persists beyond
30 minutes after discontinuing
the transfusion, another
diagnosis should be strongly
considered.

Graft-vs-Host rash, fever, diarrhea, viable T lymphocytes in Rare Irradiat

Disease GVHD cytopenia and liver blood components are compon
dysfunction 3-4 weeks after transfused, engraft and The Blo
transfusion react against the be appr
recipient's tissues and immune
the recipient is unable to diagnos
reject the donor patient
lymphocytes because of compon
immunodeficiency, for tran
severe immuno
immunosuppression, or patients
shared HLA antigens compon
associated with bone directed
marrow transplantation. donors
Transfusion associated irradiat
GVHD occurs. It of blood
typically. Transfusion contain
associated GVHD compon
carries a very poor the red
prognosis. and inc
potassiu
compon
no appa
platelet
 Fresh F
(FFP) a
cryopre
(CRYO
irradiat
these co
not con
viable l
cause G

Non-immune hemoglobinemia and Lysis of red cells can Rare

Hemolysis hemoglobinuria Transient
hemodynamic, pulmonary and
renal impairment may occur.
cardiac arrhythmia due to
yyperkalemia may occur,
particularly in patients with
renal failure.
occur due to improper
storage, handling, or
transfusion conditions.
mishandling or storage
of blood components
the contents of the blood
bags are available for
study. The blood bag
together with attached
tubing and intravenous
fluids should be saved
for further
investigations.

Post-transfusion thrombocytopenia that is the patient makes an Rare Platelet

purpura (PTP) frequently profound, purpura, alloantibody in response of very
or bleeding to platelet antigens in PTP; ho
Febrile reactions have been the transfused blood that therape
reported retrospectively with for a period of time exchang
the implicated transfusion causes destruction of benefic
autologous antigen autolog
thrombocytopenia typically 7- negative platelets do not s
48 days after transfusion circulat
PTP must be differentiated expecta
from the far more common transfus
alloimmunization to platelet regardle
antigens. Consultation with a matchin
Blood Bank physician is better.
recommended in evaluating Reserve
such patients. transfus
patients
bleedin
 IF A TRANSFUSION REACTION IS SUSPECTED
Stop the transfusion immediately!
Disconnect the intravenous line from the needle. Do not disconnect the unit from the IV
set. Attach a new IV set and prime with saline, or flush the line with the normal saline
used to initiate the transfusion and reconnect the line. Open the line to a slow drip. In
certain cases, such as a mild urticarial reaction or the presence of repeated chill-fever
reactions, it may be possible to restart the blood transfusion after evaluation and
treatment of the patient. To reinitiate the transfusion using a new IV tubing set, enter the
second port to reduce the chance of bacterial contamination.
Seek medical attention immediately. If the patient is suffering cardiopulmonary
collapse, and medical attention is not immediately available, press the blue "Code" button
and telephone the Cardiac Arrest Team (dial 911).
Check to ensure that the patient name and registration number on the blood bag label
exactly with information on the patient's identification
wristband attached to his/her wrist. DO NOT BYPASS THIS STEP BY ASSUMING
THAT THE PATIENT'S TRUE IDENTITY IS KNOWN.
Do not discard the unit of blood that has been discontinued because it may be necessary
for the investigation of the transfusion reaction.
• Notify the Blood Bank that a transfusion reaction has occurred and briefly describe the
nature of the reaction.
• Blood Bank personnel will identify the Pathology House officer or staff pathologist who
will assume responsibility for investigation of the reaction.
• Delay the transfusion of additional units until the possibility of serological
incompatibility has been investigated. Consult a Blood Bank physician if there is an
urgent need or transfusion.
• Initiate the Transfusion Reaction Report Form after Blood Bank personnel have been
notified of a transfusion reaction. It is essential that this form be filled out completely,
including the unit numbers of all blood transfused. The form will serve as a written
request for investigation of the reaction by a Blood Bank physician.
• In the case of a suspected hemolytic transfusion reaction (not urticaria alone), the
following items should be submitted promptly to the Blood Bank:
completed Transfusion Reaction Form (white copy)
posttransfusion blood specimens (Adults: 10 mL clot and 5 mL EDTA, lesser
volumes for pediatric patients), and
incriminated unit(s) of blood and attached tubing.

Restarting a Transfusion If the Blood Bank physician, after review of the clinical
information, believes the transfusion can be restarted, do not disconnect the unit. This
may apply to patients who might manifest urticarial reactions or repeated chill-fever
reactions.
Additional blood specimens may be requested, depending on the serological findings.
The venipuncture to obtain these blood specimens must not be traumatic. Small lumen
 catheters should not be used to collect blood specimens for a transfusion reaction
investigation. If red cells are hemolyzed during the venipuncture or collection, the serum
will turn pink and it may be erroneously concluded that intravascular hemolysis has
occurred.
The IV tubing used to transfuse the blood components should be clamped and sent
without the needle attached. A urine sample is not required for the routine evaluation of a
transfusion reaction, but may be requested by the Blood Bank physician in the course of
further assessment.
Patient care personnel will be notified by telephone of significant findings of the reaction
evaluation as soon as possible. A written report of the investigation, on the Blood
Transfusion Reaction Form, will be returned to the patient care unit at a later date for
inclusion in the patient's chart.
TREATMENT OF TRANSFUSION REACTIONS
The following guidelines should be tailored to suit individual cases.

Reaction Type Treatment - Adult Pediatric Follow-up

Acute Diuretic therapy: Initially, give 40-80 Pediatric dose: 1-2 Treat shock and dissemina
Hemolytic mg Furosemide (Lasix) intravenously. mg/kg/dose. May intravascular coagulation
Reactions Acute This dose can be repeated once. Lack repeat once at 2-4 measures if and when they
Hemolytic of response to furosemide in 2-3 hours mg/kg.
Reactions indicates the presence of acute renal
failure.

Water loading: The patient should be Pediatric patients

hydrated to maintain urinary output of should receive a
at least 100 mL/hr until urine is free of smaller loading
hemoglobin. volume of fluid in
Infuse a loading dose of 0.9% sodium proportion to their
chloride or 5% dextrose in 0.45% body surface area.
sodium chloride. Chart hourly urine
output. Maintain the urine output by
administering intravenous fluid at 100
mL/hour until the urine is free of
hemoglobin. If the patient's urinary
output does not increase, with this
hydration any additional fluids should
be infused with caution.

Delayed Specific treatment generally is not Supplemental transfusion

Hemolytic necessary lacking the antigen corresp
Transfusion offending antibody may b
Reactions compensate for the transfu
have been removed from t
Allergic Antihistamines(e.g., Benadryl). Give
Transfusion 50-100 mg orally or intravenously. If
Reactions urticaria develops slowly,
antihistamines may be given orally.
Pediatric dose: 1-2 Routine use of Benadryl a
mg/kg intramuscularly for all transfusions, regard
or intravenously for of allergic reactions, is dis
25-50 mg per average
dose.

Aminophylline for wheezing, at a dose Pediatric dose: 3

of 125-250 mg intravenously slowly mg/kg/dose in
over a period of about five minutes intravenous drip over
of 20 minutes.

Epinephrine for severe, acute Pediatric dose: 0.03

reactions including laryngeal edema or mL/M2 (0.03 mg/M2
bronchospasm Give 0.1-0.5 mg (0.1- of a 1:1000 solution)
0.5 mL of a 1:1000 solution) given subcutaneously.
subcutaneously. Subcutaneous dose A single pediatric
may be repeated at 10-15 minute dose should not
intervals. The total subcutaneous dose exceed 0.3 mg.
in a 24-hour period, with rare
exception, should not exceed 5 mg.

Febrile Premedicate the patient with Aspirin will adversely affe

Transfusion acetaminophen or other antipyretic platelet function, so non-a
Reactions agents when previous reactions have antipyretic agents are pref
been extremely bothersome. Pediatric
dose: 10 mg/kg to a maximum of 600
mg.

Severe shaking (rigors) can be controlled by the Note: Demerol may cause
chills sedative effect of Benadryl or Demerol respiratory arrest. An opia
(25-50 mg given intramuscularly or (Narcan) should be immed
intravenously available.

Sepsis Due to Treatment of septic shock includes:

Bacterial terminating the suspected transfusion
Contamination immediately, cardio-vascular and
of Donor Blood respiratory support, blood culture of
the patient, and administration of broad
spectrum antibiotics including anti-
pseudomonas coverage if the blood
component involved is Red Blood
Cells.

POSTTRANSFUSION DISEASES
 • All cases of suspected posttransfusion disease transmission encountered among
inpatients or outpatients, in any context, must be reported to the Blood Bank so that
they can be investigated. This allows the Blood Bank to notify the regional blood supplier
so that blood donors who are thought to be infectious can be excluded from the list of
eligible donors.
• Because of the risk of posttransfusion infection, the benefits associated with blood
transfusion must always be weighed against possible risks.
• Units of blood and blood components transfused in the University of Michigan Hospitals
are obtained from volunteer donors. Screening tests are performed on all units, including
those obtained from designated/directed donors.
• Current testing: syphilis, HBsAg, antibodies to HIV-1/2, Hepatitis C virus, anti-HBc and
HTLV-I/II, as well as, nucleic acid testing (PCR) for HIV, hepatitis C virus and West
Nile Virus.
• Additional tests for transfusion transmitted disease will be implemented in response to
federal or accrediting agency regulations or changes in the standard of care.
Unfortunately, no specific screening test is currently available to detect all forms of
hepatitis.
• Under extremely rare circumstances it may be necessary to transfuse blood or a blood
component to a patient before the above screening tests for disease transmission have
been completed. In such situations, the physician treating the patient will be made aware
of the available options by Blood Bank medical staff and will be informed of the test
results as soon as they are available.
• Units of blood negative for anti-CMV can be provided for selected patients undergoing
allogeneic bone marrow homotransplantation. CMV safe components may be provided
through the use of leukocyte-reduced cellular blood components.
• Guidelines for treatment of hospital personnel who have accidentally inoculated
themselves with blood are available in Employee Health Service and Emergency
Services.
Look Back Notification
When donors of previously transfused units are found, at a subsequent donation, to be
positive for HIV, hepatitis C, HTLV or other diseases as determined by the public health
service, the Blood Bank is required by federal regulation to notify the patient. We usually
will notify the patient’s physician for assistance in contacting the patient. This process is
known as "look back".
Version July 2004

Transfusion Reactions
A. General.
The resident will generally only be contacted for a transfusion reaction report on the weekend or
at night for one of the following conditions:
1. Positive DAT on post-transfusion sample.
2. Evidence of free hemoglobin on post-transfusion sample.
 3. Clerical error (wrong blood given).
4. Life-threatening symptoms reported (e.g. cardiac arrest or death).
5. Second reaction reported in same patient in less than two weeks.
Do not delay investigation of a reported transfusion reaction because of incomplete paperwork.
The paperwork can be completed later. We do not need a physician's signature to proceed.
B. Materials needed for evaluation.
For all acute reactions other than rash/urticaria alone or volume overload alone, we request the
following:
1. Post-transfusion blood (red top tube and purple top tube)
2. Post-transfusion urine (collected ASAP after reaction)
3. Return of implicated blood bags with attached tubing and blood tags
4. Transfusion reaction report form
C. Need for further transfusions.
VERY IMPORTANT: If at all possible, further transfusions should be delayed until completion
of the transfusion reaction work-up. If a transfusion must be given right away, the patient must
receive uncrossmatched group O RBCs issued on a blue card (or group AB plasma). We must
assure the patient's ABO group is correct before issuing further ABO specific blood. Any ABO
group specific units that have already been crossmatched (but not transfused) cannot be used
unless they are group O. You must ask if any such units are present outside of the blood bank,
e.g. in the OR or ICU refrigerator. If so, THESE UNITS MUST BE RETURNED TO THE
BLOOD BANK IMMEDIATELY!!!! These units must not be transfused prior to completion of
the work-up, and if they are left up on the floor, the temptation to transfuse them may be too
great. The nursing staff/physicians may resist sending the units back, but you must be firm and
assure them that they can have group O blood if emergency transfusion is necessary. We must
assume they are ABO incompatible until proven otherwise.
D. Acute hemolytic transfusion reaction.
This is a life-threatening EMERGENCY. It is almost always due to the transfusion of ABO-
incompatible RBCs with resulting intravascular hemolysis, complement activation, and
coagulopathy. Stop whatever else you are doing and make sure the clinicians know that there is
evidence that incompatible blood was given, so that appropriate treatment can be rendered.
Hopefully, they will already know, but please make sure. Do not assign blame at this point. If the
clinicians ask for treatment advice, remember that vigorous hydration is the most important
therapeutic step at this point. Lasix may be administered to preserve renal function. Supportive
measures should be taken as appropriate (e.g. pressors). Document who you spoke to and when.
Make sure a Transfusion Service faculty member knows about the reaction (as time allows).
If the incompatible blood was issued due to mislabelling of a patient cross-match sample, it is
important to make sure we identify what patient is on the other end of that specimen switch. For
example, if patient X is blood group A and patient Y is blood group B and their pretransfusion
testing sample labels were switched, both patient X and patient Y are at risk of getting
incompatible RBCs. Even in a case involving groups A and O, for example, one patient is at risk
for incompatible RBCs and the other for incompatible plasma products.
E. Febrile, nonhemolytic transfusion reactions.
This is defined as a rise in patient body temperature by greater than or equal to1oC with no other
obvious explanation. We must always rule out the possibility of an acute hemolytic transfusion
reaction, bacterial contamination of the bag, and fever due to pre-existing underlying disease. If
no other explanation exists, fever may be due to the transfusion. Physicians should always take
the presence of fever seriously, stop the transfusion, and send the bag and post-transfusion
samples for work-up in the laboratory. Acute intravascular hemolysis may present as fever alone.
If the fever is quite high or accompanied by hypotension, or if you are very suspicious of sepsis,
make sure the blood bag is cultured. The blood bank techs will arrange this with the
microbiology lab at your request.
Following the occurrence of one febrile reaction, we recommend the use of antipyretics (e.g.
Tylenol) prior to future transfusions. Some physicians may already have used antipyretics, as
they can make the patient feel much more comfortable during the transfusion. If so, continued
use is suggested. If they choose not to administer antipyretics, that is their perogative. You might
reassure a reluctant physician, however, that the use of antipyretics prior to transfusion should
not mask the significant fever that would accompany a serious reaction such as acute hemolysis
or sepsis. Multiply transfused patients especially benefit from pre-medication.
Generally, we do not start using leukocyte-reduced blood components for a patient until they
have had two recorded febrile transfusion reactions. The statistics say that only 1 in 8 patients
will ever have a second febrile reaction, therefore the use of expensive, leukoreduced blood is
often unnecessary. However, you may want to make an exception to the rule in certain instances:
For example, in a patient who is particularly ill who has had numerous transfusions already (so
they are at relatively higher risk), or if the clinician is particularly insistent. Another instance
might be a patient with a complicated serological picture in whom working up a febrile
transfusion reaction would entail a lot of work. I would also probably issue leukoreduced blood
if the patient has a history of febrile reactions, but they have not all been formally work-up by
the blood bank, and thus are not documented by us.
DO NOT APPROVE THE USE OF WASHED RED BLOOD CELLS for the prevention of
febrile reactions!!!! This is an outmoded practice. The clinicians may ask for washed blood, and
some older texts may say to use it, but leuko-reduction filters are 100 to 1000 times more
efficient and easier for the staff. Plus, there should be no delay obtaining a leukoreduced unit
from inventory, where washing will take close to an hour to perform.
Patients having fever despite getting leukoreduced blood. Occasionally a multitransfused
patient will suffer a febrile reaction despite receiving a leuko-reduced unit of blood. This may
occur in individuals with particularly high anti-leukocyte antibody titers. Remember that
leukoreduction still leaves behind somewhere in the neighborhood of 100,000 WBCs in each
unit. This situation does not call for switching to the use of washed RBCs! As noted above,
washing is significantly less efficacious and will not improve the symptoms. Similarly, the use of
washed and leukoreduced RBCs is not likely to improve the patient's symptoms because of the
minimal increased WBC removal of washing and has the downside of giving the unit a 24 hour
shelf life and loss of some of the RBCs, as well.
The presence of cytokines is one of the latest theories to explain these reactions. If fevers persist
in spite of the use of leukoreduced blood, you may want to suggest that the freshest units be
selected for leukofiltration. Thus, fewer cytokines would theoretically be present in these units.
Fever in a patient with no prior transfusion or pregnancy history. Patients having their first
ever transfusion may experience fever even though they have had no opportunity to previously
be sensitized to WBC antigens. This phenomenon may be explained by the presence of cytokines
in transfused plasma.
F. Allergic reactions.
Mild reactions involving the skin only (rash, urticaria, itching) do not need to be worked-up by
the blood bank or even reported to us. The clinicians may administer an anti-histaminic agent
(e.g. Benadryl) and if the allergic symptoms subside, the transfusion of that unit may continue. If
the skin symptoms persist, we would suggest stopping that unit and trying a different one (in
addition to the use of anti-histamines). If a mild, skin-only reaction is reported to the laboratory
and specimens sent, we generally go ahead and complete a transfusion reaction investigation,
although it does not accomplish anything in nearly every case.
If symptoms beyond skin involvement are reported, the transfusion should be stopped, and the
remainder of that unit sent back to the laboratory. Examples to watch out for are facial swelling,
itching of the throat, or dyspnea. These symptoms may be the first inkling of a more serious
allergic reaction developing and should be taken seriously. Development of anaphylaxis is not
uncommon and is a life-threatening emergency. You may be contacted when this occurs. Your
job is to assess further transfusion needs and decide how to meet them. You may want to suggest
a work-up of the recipient for IgA deficiency. The work-up should first involve a total IgA level
and tryptase determinations (done in Immunology on a red top tube. The tryptase level should
preferentially be collected within 2-3 hours of the reaction). If that is within normal limits, a
more detailed evaluation for missing subtypes of IgA and the presence of corresponding
antibodies may be indicated. This is a send-out test through Immunology. In the meantime,
careful consideration should be given to additional transfusion needs. RBC components should
be thoroughly washed, but plasma and platelet transfusions will be problematic. Close
observation and slow infusion should be carried out in any case as well as premedication with
anti-histamines and possibly steroids. If IgA deficiency is diagnosed, refer to the section on IgA
deficiency for transfusion options.
G. Bacterial contamination.
When a patient has symptoms of high fever and shock or other symptoms suggestive of sepsis
(e.g. DIC) during or within 90 minutes of ending the transfusion, consider the possibility that one
of the transfused units of blood was contaminated with bacterial growth. RBC components are
especially at risk for the growth of gram-negative, endotoxin-producing organisms such as
Yersinia enterocolitica. These organisms thrive in a blood-rich medium at refrigerator
temperatures. Their growth generally reaches significant levels in blood stored for 21 days or
longer. Please remember to culture the blood bag (and have the recipient's blood cultured) if
suspicion is high for this situation, such as in the following clinical situations:
• Temperature increase > or = 2C and severe shaking chills or decrease in
systolic blood pressure > 30mm
• "Warm type" shock (hypotension and skin flushing)
• High fever (> or = 39C)
A culture utilizing a sealed segment from the blood bag is not adequate, as the segments may not
show bacterial growth. Ask for a gram stain of the remaining blood to be performed
immediately, if possible, to get immediate information about possible bacterial presence. Gram-
negative sepsis from transfusion can be devastating, and is fatal within hours in a high
percentage of patients. Initial treatment involves managing the septic shock, which may include
immediate i.v. administration of broad spectrum antibiotics and the use of steroids and
vasopressor drugs, such as dopamine. Antibiotic therapy concurrent with the administration of
the unit will not blunt the effects of the endotoxin. Platelet components may also be
contaminated with bacteria, although these are more commonly gram-positive organisms that
were skin contaminants on the donor.
H. Transfusion Associated Acute Lung Injury (TRALI).
The most significant feature of TRALI is bilateral pulmonary "white-out" on x-rays which is
most likely caused by trapped donor white cell antibodies/recipient WBC agglutinates.
Supportive care to maintain oxygenation as all that is required for treatment. The infiltrates will
slowly resolve with no harmful sequela.
I. Delayed hemolytic transfusion reactions.
You may be contacted if the blood bank discovers that a delayed hemolytic transfusion reaction
has taken place. Please make certain that the clinical team knows of the diagnosis and will
monitor the patient carefully for signs of ongoing hemolysis and worsening anemia. Otherwise,
no action is generally required.
J. Risk of all adverse effects of transfusion.
See appendix 7 in paper supplement for estimates of risk.
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