Transfusion Medicine Quality Manual
Guidelines for Investigation of Adverse Transfusion
Reactions
Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
1. Policy Statements
1.1
All adverse reactions shall be immediately reported to the Transfusion
Medicine (TM) Laboratory.
1.2
The TM Laboratory shall investigate all reports of adverse reactions. The
investigation shall determine the probable cause and shall include
appropriate laboratory tests.
1.3
Donor units and patient blood cultures shall be sent to the microbiology
laboratory whenever there is investigation of suspected transfusion
transmitted bacterial contamination.
1.4
The following tests shall be performed as soon as possible to rule out an
Acute Hemolytic Transfusion Reaction:
1.4.1
1.4.2
1.4.3
1.4.4
Clerical check;
Visual inspection of post-transfusion specimen for hemolysis;
Direct Antiglobulin Test, post-transfusion specimen;
Regrouping of recipient’s pre- and post-transfusion specimens,
implicated blood component unit and other units transfused within
6 hours of the reaction (if available).
1.5
The anti-human globulin (AHG) reagent used for a Direct Antiglobulin Test
shall contain antibodies to IgG and the C3 component of complement
(polyspecific AHG).
1.6
The following tests shall be performed on pre and post transfusion samples,
if pre-transfusion samples are available:
1.6.1
1.6.2
1.6.3
1.6.4
Direct Antiglobulin Test on pre-transfusion specimen (if not
performed during pre-transfusion testing) if post–transfusion
specimen is positive;
Repeat Indirect Antiglobulin Test (Antibody Screen) on recipient’s
pre- and post-transfusion specimens;
AHG crossmatch of implicated unit and other units transfused
within 6 hours of the reaction (if available) using recipient’s preand post-transfusion specimens.
Gram stain and culture of implicated unit(s) if required;
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
1.6.5
1.7
1.8
Blood cultures (from recipient prior to antibiotic therapy) if
required;
1.6.6 Urinalysis; and
1.6.7 Additional testing as requested by physician.
Transfusion reactions due to plasma protein products are documented on an
adverse events form and forwarded to the transfusion medicine laboratory.
Transfusion reactions with suspected hemolysis due to IVIG require the
following tests to be performed on the post-transfusion sample:
1.8.1
1.8.2
1.8.3
1.8.4
1.8.5
ABO/RH testing;
Indirect Antiglobulin test (IAT);
Direct Antiglobulin test (DAT);
Elution (if required). When testing the eluate ensure reagent A
cells and B cells are included. This will identify passively acquired
anti-A1 or anti-B as IVIG may contain blood group antibodies
which cause a positive (DAT) and hemolysis; and
Additional testing as requested by physician.
2. Linkages
Standard Operating Procedure for ABO Grouping Tube Method. Available at:
http://www.health.gov.nl.ca/health/bloodservices/pdf/sop_for_abo_grouping.pdf
Standard Operating Procedure for Rh Typing Tube Method. Available at:
http://www.health.gov.nl.ca/health/bloodservices/pdf/sop_for_rh_typing.pdf
Standard Operating Procedure for Performing the Direct Antiglobulin Test.
Available at:
http://www.health.gov.nl.ca/health/bloodservices/pdf/performing_the_direct_anti
globulin_test_ver3.pdf
Standard Operating Procedure for Indirect Antiglobulin Crossmatch. Available at:
http://www.health.gov.nl.ca/health/bloodservices/pdf/sop_for_Indirect_Antiglobu
lin_(AHG)_Crossmatch_ver2.pdf
Standard Operating Procedure for Patient History Check. Available at:
http://www.health.gov.nl.ca/health/bloodservices/pdf/patient_history_check.pdf
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
Standard Operating Procedure for Patient Identification and Specimen Labeling.
Available at:
http://www.health.gov.nl.ca/health/bloodservices/pdf/patient_id_and_specimen_la
beling.pdf
Guideline for investigation of suspected transfusion transmitted bacterial
contamination. Available at:
http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/08vol34/34s1/34s1-eng.php
Reporting Adverse Transfusion Events. Available at:
http://www.health.gov.nl.ca/health/bloodservices/pdf/reporting_adverse_events.p
df
Algorithm: Suspected Transfusion Reaction . Available at:
http://www.health.gov.nl.ca/health/bloodservices/pdf/algorithm_suspected_transf
usion_reactions.pdf
Canadian Blood Services requisition for TRALI investigation. Available at:
https://www.blood.ca/sites/default/files/TRALI_Patient_Data.pdf
Canadian Blood Services requisition for Patient Request for IgA/Anti-IgA
Testing. Available at:
https://www.blood.ca/sites/default/files/CL2012-D01_Patient-request-form.pdf
Canadian Blood Services requisition for Platelet Immunology. Available at:
https://www.blood.ca/sites/default/files/Diagnostic_Services/MB/MB-PlateletImmunology-Requisition.pdf
3. Scope
3.1 All transfusion medicine laboratory technologists.
3.2 Responsible Hematologist/Hematopathologist.
4. General Information
4.1 All adverse reactions must be documented. Serological investigation is not
required in the following circumstances UNLESS ordered by the attending
physician.
4.1.1
The only sign/symptom is a mild rash <2/3 of the body surface area,
pruritus, urticaria, or flushing; OR
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
4.1.2
The only sign/symptom is a temperature ≥ 38°C and <39°C and >1°C
above baseline.
4.2
Pink or red discoloration in the post-transfusion specimen but not in the pretransfusion specimen is suggestive of intravascular red cell destruction and
release of free hemoglobin.
4.3
If post-transfusion specimen is not collected until 5-7 hours after an acute
hemolytic episode, hemoglobin degradation products, especially bilirubin,
may cause a yellow or brown discoloration of the plasma. Bilirubin may
begin to rise as early as one hour post reaction, peak at 5-7 hours and
disappear within 24 hours if liver function is normal.
4.4
If transfused incompatible red cells have been coated with antibody and not
immediately destroyed, the post-transfusion reaction DAT will likely be
positive, frequently with a mixed field agglutination pattern. If there is a
delay in collection of the post reaction specimen and the transfused cells
have been rapidly destroyed, the DAT may be negative.
4.5
Examination should be performed on the centrifuged supernatant fluid of a
freshly collected urine specimen. In acute hemolytic transfusion reactions,
free hemoglobin released from damaged cells can cross the renal glomeruli
and enter the urine. If previously intact red cells in a specimen undergo invitro hemolysis during transportation or storage, misleading free
hemoglobin may be present.
4.6
Suspect a faulty infusion device or the addition of an incompatible solution
if blood in the administration tubing and/or the donor unit is hemolysed. For
example, 5% dextrose in water will hemolyze red cells.
4.7
Suspect the use of an incompatible solution if the blood in the
administration tubing is clotted. For example lactated Ringer's solution, can
cause clots to form in blood.
4.8
Platelets, due to their storage temperature, are the most common blood
component implicated in suspected bacterial contamination reactions.
4.9
Initiation of treatment for suspected bacterial contamination should be based
on the patient’s clinical presentation as a delay in treatment may result in
severe morbidity or death.
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
5. Process
5.1
Quality Control
5.1.1
5.1.2
5.1.3
5.1.4
5.2
All reagents are used and controlled according to the manufacturer’s
written instructions.
All reagent antisera and red cells are controlled each day of use.
All anti-sera must be visually inspected for contamination such as
discoloration, cloudiness, turbidity and/or particulate matter.
All reagent red cells must be visually inspected for hemolysis and/or
discoloration.
Procedure
5.2.1 Collect post-transfusion specimens, as required:
5.2.1.1 EDTA specimen;
5.2.1.2 Urine;
5.2.1.3 Specimens for other tests which may be requested by physician;
5.2.1.4 A minimum of one set of blood cultures (aerobic and anaerobic
bottles) should be collected if there is a combination of symptoms
which include fever, tachycardia, hypotension, chills, rigors,
nausea, vomiting, diarrhea, dyspnea, oliguria, other signs of shock
or a high suspicion of bacterial contamination without
sign/symptom presentation.
5.2.1.5 Obtain post- transfusion reaction specimens, facility adverse
transfusion reaction reporting form, blood unit with compatibility
tag attached, administration set and attached IV solutions, if
available. If several units have been transfused in succession, all
units given in the past six (6) hours will be investigated (if
available) as a possible source of the reaction. In certain
circumstances, such as a suspected delayed hemolytic transfusion
reaction, the physician or designate may request additional donor
unit testing.
5.2.2 Perform a clerical check:
5.2.2.1 Check compatibility tag attached to donor unit for errors. Ensure
the blood types of the recipient and donor unit are compatible and
that the correct tag is attached to the correct donor unit.
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
5.2.2.2 Ensure that the recipient’s name and unique identification number
on the pre-transfusion specimen, requisition and worksheet match
exactly with the name and unique identification number on the
compatibility tag.
5.2.2.3 If a clerical error is discovered:
5.2.2.3.1 Notify Transfusion Medicine Supervisor or designate, and
the attending physician or designate;
5.2.2.3.2 Initiate a search of records to determine if other patients are
at risk due to error; and
5.2.2.3.3 Review the recipient’s transfusion history (if available) for
previous adverse transfusion reaction.
5.2.3 Confirm proper labeling of the post-transfusion sample. The label
on the post-transfusion specimen(s) must include recipient’s name,
unique identification number, the date/time of collection and the
identity of the phlebotomist. Ensure the recipient’s name and unique
identification number on the post transfusion specimen(s) matches that
on the adverse transfusion reaction reporting form.
5.2.4 Perform a visual check for hemolysis. Centrifuge post-transfusion
blood specimen and visually compare the color of the plasma to pretransfusion specimen for evidence of hemolysis/ icterus. If hemolysis
is observed in post-transfusion specimen, a second specimen should be
obtained to confirm the hemolysis in the first specimen was not due to
improper collection technique.
5.2.5 Perform Direct Antiglobulin Test (DAT) on post-transfusion
EDTA specimen. If DAT on post-transfusion specimen is positive,
test specimen using monospecific IgG and C3 reagents. If DAT is
positive due to IgG and/or C3, perform elution.
5.2.6 Perform ABO/ Rh typing on pre and post-transfusion specimens.
If post-transfusion ABO/ Rh typing differs from the pre-transfusion
ABO/ Rh typing, notify Transfusion Medicine Supervisor or designate
and the attending physician or designate. Initiate appropriate search to
determine if another patient may be at risk.
5.2.7 Perform ABO/ Rh typing on donor unit(s). Notify blood supplier if
discrepancy detected.
5.2.8 Perform DAT on pre-transfusion specimen if not performed
during pre-transfusion testing. If DAT on pre-transfusion specimen
is positive, test specimen using monospecific IgG and C3 reagents. If
DAT is positive due to IgG and/or C3 and the recipient has been
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
5.2.9
5.2.10
5.2.11
5.2.12
5.2.13
5.2.14
transfused or pregnant within the past three months or the recipient’s
transfusion history is unknown, perform elution.
Perform an Indirect Antiglobulin Test (IAT) on pre and posttransfusion specimens using original pre-transfusion method.
5.2.9.1 If the post-transfusion IAT is positive, perform an antibody
identification;
5.2.9.2 If the pre-transfusion IAT is positive, perform an antibody
identification ; and
5.2.9.3 If an antibody identified, phenotype the transfused units for
the corresponding antigen.
Perform an Anti Human Globulin (AHG) crossmatch on donor
unit(s) using pre and post-transfusion specimens. The AHG
crossmatch method must be used for transfusion reaction investigation
regardless of original method, i.e. immediate spin, computer
crossmatch or AHG.
If indicated, following completion of the investigation, forward the
transfusion reaction donor unit(s) that have been transfused within
four (4) hours of the end of transfusion, administration set(s) and
attached IV solutions, if any, to the Microbiology / Bacteriology
Laboratory for culture. If transport to the Microbiology/ Bacteriology
Laboratory is delayed, refrigerate the donor unit(s), administration set
and attached IV solutions, if any.
Enter results if the transfusion reaction investigation into the LIS as
per facility policy.
Notify the attending physician/designate or nurse with results of
serological investigation.
Document details of date, time and the name of the person notified.
5.3 Guidelines
Refer to Public Health Agency of Canada link.
5.4 Materials
5.4.1
Blood component unit which was implicated in adverse transfusion
reaction, with the compatibility tag attached, the administration set
(without needle) and the IVsolutions (if any).
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
5.4.2
5.4.3
5.4.4
5.4.5
5.4.6
5.4.7
All blood component units (if available) transfused within 6 hours of
the reaction. If the units are not available, the testing may be
performed on the corresponding segments retained by the TM lab.
Pre-transfusion specimen.
Post- transfusion reaction blood specimens (EDTA specimen, blood
cultures, specimens for other tests requested by physician, correctly
labelled.
First voided urine post adverse transfusion reaction, correctly labelled
Blood banking reagents required for testing of specimens.
Facility adverse transfusion reaction reporting form or occurrence
form (computer or paper).
6. Acronyms
AHG
Antihuman globulin
ATR
Adverse transfusion reaction
DAT
Direct antiglobulin test
IAT
Indirect antiglobulin test
SOB
Short of Breath
TM Laboratory
Transfusion Medicine Laboratory
LIS
Lab Information System
ATR investigation profile
Adverse transfusion reaction investigation
profile. Tests as outlined in the procedure.
7. Definitions
Antibody screen
use of selected red cells with known
antigen composition for the major blood
groups to identify unexpected clinically
significant allo-antibodies detected in
plasma or serum
Bilirubin
a yellow bile pigment formed in blood
from haemoglobin during normal and
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
Bronchospasm
Crossmatch
Cyanosis
Diaphoresis
Direct Antiglobulin Test
Dyspnea
Edema
Elution
Erythema
Erythroderma
Fever
Hypertension
Hypotension
Hypoxemia
Oliguria
Orthopnea
Post-transfusion testing
abnormal destruction of erythrocytes by the
reticuloendothelial system.
contraction of smooth muscle in the walls
of the bronchi and bronchioles, causing
narrowing of the lumen
a procedure to detect incompatibilities
between a recipient and a donor prior to
transfusion
dark blue or purplish discolouration of the
skin due to deficient oxygenation of the
blood
profound sweating
a procedure used to detect in vivo
sensitization of red blood cells and
determine which protein is coating the red
blood cells.
shortness of breath (SOB)
swelling
the removal of antibodies absorbed onto
the red cell surface for the purpose of
antibody identification
redness of the skin
intense and widespread reddening of the
skin
an increase in temperature of > 1°C from
pre-transfusion value and ≥ 38°C
an increase of greater than or equal to
30mm Hg systolic
drop in systolic BP of greater than or equal
to 30 mmHg and systolic BP less than or
equal to 80 mmHg.
subnormal oxygenation of arterial blood,
PaO2/ FiO2 less than 300mm Hg or O2
saturation less than 90% on room air
new onset decrease in urinary output within
72 hours of the identification of the adverse
reaction (<500cc/ 24 hours)
discomfort in breathing brought on or
aggravated by lying flat
testing performed after a transfusion to
investigate a suspected adverse transfusion
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
reaction
itching
Pruritis
Rigors
Shortness of Breath (SOB)
Tachycardia
Tachypnea
Urinalysis
Urticaria
generalized, involuntary shaking that
occurs during a fever
a new onset or significant worsening of
shortness of breath or a significant increase
in respiratory rate, with or without
hypoxemia
increased heart rate greater than or equal to
120 beats/ minute or heart rate greater than
or equal to 40 beats/ minute from baseline
rapid breathing
examination of urine collected after a
suspected transfusion reaction for detection
of free hemoglobin and/ or bilirubinuria
raised red spots with or without pruritis
8. Records Management
8.1 The transfusion medicine laboratory shall retain the recipient administration
data file indefinitely.
8.2 All administration records in the recipient’s medical chart shall be retained in
accordance with the health care facility policy.
8.3 Temperature monitoring records for blood components and blood products
shall be retained a minimum of five years.
8.4 The report of an adverse transfusion reaction shall be placed in the recipient’s
health record:
8.4.1
The report of investigation of all serious adverse transfusion reactions
shall be retained in the transfusion medicine laboratory indefinitely;
and
8.4.2 Recommendations pertaining to special blood component requirements
or preparation requirements for subsequent transfusions shall be placed
in the recipient’s transfusion history
8.5 Each facility shall have a record system that ensures a copy of all information
relating to the patient and the administered blood component or blood product
forms a permanent record for the patient:
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
8.5.1
8.5.2
The record system shall be organized and maintained in such a way
that it is possible to trace blood components or blood products from
distributor to final disposition (i.e. transfusion, administration or
destruction); and
The records system shall also provide a means to locate and access all
records in the facility related to a given product.
9.0 Key Words
Adverse, Reaction, Transfusion
10.0 Supporting Documents
10.1 Tables/Charts
Table of Recommended Tests
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Guidelines for Investigation of Adverse
Transfusion Reactions
Provincial Blood
Coordinating Program
References .
Canadian Society for Transfusion Medicine. (2011). CSTM standards for hospital
transfusion service. Version 3. Ottawa: Author.
Health Canada. (2013). Blood regulations. Canadian Gazette, Part II, 147(22),
pp. 2247-2314.
AABB. (2014). Standards for blood banks and transfusion services (29th ed.).
AABB: Bethesda, Maryland.
Canadian Standards Association. (2010). Blood and blood components, Z902-10.
Mississauga, ON: Author
Mazzei, C.A., Popovsky, M.A., & Kopko, P.M. (2014). In M. K. Fung, B. J. Grossman,
C. D. Hillyer , & C. M. Westhoff (Eds.). Technical Manual (18th ed.),
Bethesda, MD: AABB Press.
Callum, J., Lin, Y., Pinkerton, P.H., Karkouti, K., Pendergast, J.M., Robitaille,
N…Webert, K.E. (2011). Bloody easy 3. Toronto, ON: Ontario Regional Blood
Coordinating Network.
Stedman, T. (2006). Stedman's Medical Dictionary (28th ed.). Baltimore, US: Stegman
Public Health Agency of Canada. (2008). Guideline for investigation of suspected
transfusion transmitted bacterial contamination. Retrieved February 16.2015,
from http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/08vol34/34s1/34s1-eng.php
Mazzei, C. A., Popovsky, M. A., & Kopko, P. M. (2014). Noninfectious Complications
of Blood Transfusion. In M. K. Fung (Ed.), AABB (18th ed., pp. 665-696).
Bethesda, MD: AABB Press
CSL Behring Canada Incorporated. (2014) Hizentra: Product monograph.
Retrieved from http://www.cslbehring.ca/canadian-products-monographs
AABB Center for Patient Safety. (2012) Retrieved from:
http://www.aabb.org/programs/safetycenter/Documents/AABB-Center-forPatient-Safety-Flyer.pdf
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