Download Slide 1

ADVERSE TRANSFUSION
EVENTS
HEMATOLOGY ROUNDS
August 23, 2012
D.K. Towns, MD, FRCPC (Anesthesia)
Medical Director
Canadian Blood Services
Calgary, AB
OVERVIEW OF THE
CANADIAN BLOOD SYSTEM
2
The blood system in Canada is complex
Regulator
Health Canada
Blood Suppliers
Canadian Blood
Services (CBS)
3
Hema-Quebec
(H-Q)
Government funding for CBS is approved by a provincial
committee.
The CBS Head Office is located in Ottawa and has overall
responsibility for:
a) developing policies and standard operating procedures
b) monitoring collection facilities and regional testing
laboratories
c) developing contracts with plasma fractionators to
fractionate CBS plasma and obtain fractionation
products
4
Regional CBS staff include administrative, medical,
nursing, technical, and recruitment personnel who are
responsible for:
a) recruiting, assessing, and monitoring donors during
blood or apheresis collections
b) processing, storing, distributing, and transporting blood
components and products to area hospitals
c) performing laboratory testing or arrange for centralized
laboratory testing
d) conducting quality control activities
e) maintaining lookback/traceback programs
5
Partners in the Health Care
system include:
1)
Hospital Transfusion Laboratories
2)
Clinical staff in hospitals
3)
The blood recipients’ physician who
orders blood transfusion
6
* Source: Courtesy of Canadian Blood Services, Clinical Guide to Transfusion, pg 13.
7
A few "facts”
• Canadian Blood Services has 43 permanent locations
and services 732 health facilities
• We have 1.74 million donors
• Only 3.7% of eligible Canadians are blood donors
(excluding Quebec)
• 21% of donors are aged 17-24
• 79% of donors are aged 25+
• 49% male/51%female
8
A few more "facts”
• Last year we collected:
–
–
–
–
–
910,220 units of whole blood
54, 432 units of apheresis plasma
54,432 units of apheresis platelets
963 units of autologous blood
189 units of blood for directed donation
• Each unit of whole blood can be made into up to
3 components:
– red blood cells
– plasma
– platelets or cryoprecipitate
9
10
Adverse Event
"An undesirable and unintended response to the
administration of whole blood or a blood
component that is considered to be definitely,
probably, or possibly related to the administration
of whole blood or blood component."
(also referred to as Adverse Transfusion Reaction,
or Adverse Transfusion Event)
11
Serious Adverse Event
• requires in-patient hospitalization or prolongation of
hospitalization directly attributable to the event
• results in persistent or significant disability or incapacity
• necessitates medical or surgical intervention to preclude
permanent damage to, or impairment of body function
• is life-threatening
• results in death
12
Unexpected Adverse Event
An adverse event that is not identified in
nature, severity, or frequency among the
currently known adverse effects associated
with the administration of blood, blood
components, or blood products (plasma
derivatives).
13
Canadian Blood Services requires that hospitals
report adverse transfusion reactions to us
We, in turn, report these reactions
to Health Canada
14
Why?
•
May result in product recall.
•
May result in donor notification and/or
investigation and/or deferral.
•
May result in recipient notification.
•
Also required for purposes of tracking and
trending (?something new; ?an unexpected
change in frequency)
15
Timelines
Serious Adverse Event resulting in Fatality:
• report immediately to MD and QAM
• report immediately to Director, Regulatory Affairs
Other Serious Adverse Event (non-fatal) or Unexpected
Adverse Event
• report as soon as possible after discovery of event to MD
and QAM
• report as soon as possible but no later than eight
working days from the discovery of the event to Director,
Regulatory Affairs
16
Canadian Blood Services’ Medical Director is
responsible for assessing the information:
• description of events preceding and following the reaction
including date, time, diagnosis, drug history, clinical
symptoms, and sequelae
• identify transfused components requiring investigation within
appropriate timeframes including donation numbers and dates
of collection
• identify and consult with the reporting facility (if required) the
feasibility of initiating additional patient/product testing
• determine ATE classification
• determine requirement for recall of companion components
and/or recall of previous donations, including final disposition
of recalled components
17
Canadian Blood Services’ Medical Director is
responsible for assessing the information (cont’d):
• determine requirement for donor deferral/notification
• determine requirement for surveillance event initiation
and addition of tests pending on next donation
• review donor record(s) in PROGESA to determine if any
associated donor(s) were ever associated with a
previous AR type of surveillance event
• determine additional comments/actions required
• defer donors if required
18
19
Clinical diagnosis
• When any unexpected or untoward sign or
symptom occurs during or shortly after the
transfusion of a blood component, a
transfusion reaction must be considered
as the precipitating event until proven
otherwise.
• Only a high index of suspicion will allow a
transfusion reaction to be diagnosed.
20
Immediate Adverse Events
Associated with Transfusion
• Acute hemolytic transfusion reaction
• Febrile non-hemolytic transfusion
reaction
• Allergic Reactions
– urticarial
– anaphylactic
• Transfusion-associated circulatory
overload (TACO)
• Transfusion-associated dyspnea
(TAD)
• Transfusion-related acute lung injury
(TRALI)
21
• Septic transfusion reaction
(bacterial contamination)
• Hypotensive reactions
–
ACE inhibitors
• Non-immune red cell hemolysis
• Metabolic disturbances
– hypothermia
– hyperkalemia
– acidosis
Risk of Complication
REACTION
RATE
Acute hemolytic transfusion reaction
1:25,000
Febrile non-hemolytic transfusion reaction
1:10
(platelets)
1:40,000
Allergic reaction: Anaphylactic
Allergic reaction: Minor
1:100
TRALI
1:5,000
TACO
1:700
22
Delayed Adverse Events
Associated with Transfusion
• Delayed hemolytic transfusion reaction
• Alloimmunization
–
–
–
–
•
•
•
•
•
Red cell antigens
HLA
Leucocytes
Platelets
Graft versus host disease (TA-GVHD)
Post-transfusion purpura (PTP)
Hemosiderosis
Viral and parasitic infections
Transfusion-related immunomodulation (TRIM)
23
Signs and Symptoms of
Transfusion Reactions
• fever/chills/rigors
• pain
• dyspnea/
respiratory distress
• bleeding
• hypotension
• hypertension
• headache
24
• nausea and
vomiting
• rash/hives
• angioedema
• flank pain
• anaphylaxis
• cyanosis
• bronchospasm
• tachycardia
• abdominal
cramps
• diarrhea
• cough
• red eye
• anxiety
• jaundice
• hematuria
Often difficult because:
• there is more than one predominant
presenting symptom
• more than one reaction going on
• atypical presentation
• underlying comorbidities unrelated to
transfusion
25
Shortness of Breath
26
Differential Diagnosis of
transfusion reaction with
shortness of breath:
•
•
•
•
•
•
•
TRALI
TACO
TAD
Anaphylaxis
AHTR
Bacterial contamination
Other etiology (unrelated to transfusion)
27
TRALI
•
•
•
•
•
Acute onset (within 6 hours of transfusion)
Hypoxemia
Bilateral infiltrates on CXRay
No evidence of circulatory overload
No pre-existing acute lung injury or other risk factors for ALI
May also have
– hypotension
– fever
– transient leucopenia
Minimal findings on chest auscultation
28
TRALI continued
TTISS (2004-2005) - 2nd highest cause of transfusion-related
morbidity and mortality
Treatment: ventilation support
80% of patients show clinical improvement within 48-96 hours
5 - 10% fatality
29
TACO
•
Acute pulmonary edema secondary to congestive heart failure precipitated by
transfusion of a blood volume greater than what the recipients circulatory
system can tolerate
(** do not need a "sick heart" to suffer iatrogenic CHF**)
•
•
•
Hypertension
Tachycardia
Positive fluid balance
Likely the most under-recognized and potentially serious transfusion complication
Risk factors:
– too much blood transfused too rapidly
– age <3 or > 60 years
– diminished cardiac reserve
– chronic (volume-compensated) anemia
30
TACO continued
Prevention
• transfuse only when indicated
• recognize patients at risk
• if at-risk, transfuse slowly
• consider diuretics
• watch fluid balance - invasive monitoring if at-risk patient or high-risk
transfusion (example: massive transfusion)
Treatment
• stop transfusion
• position patient in upright position
• supplementary oxygen
• diuretics
• cardiac and respiratory support as required
31
Transfusion Associated
Dyspnea (TAD)
European Haemovigilence Network
introduced the term to allow for classification
of respiratory distress temporally associated
with transfusion which could not be assigned
to known pulmonary reactions
32
Immediate management of a transfusion
reaction associated with shortness of breath:
• Stop the transfusion immediately
• Notify hospital blood bank of transfusion
reaction
• Maintain IV access
• Monitor patient’s vital signs
• Recheck patient ID and blood product
label
• Chest X-ray
33
Fever
34
Differential diagnosis of fever associated
with a transfusion reaction:
•
•
•
•
•
Acute Hemolytic transfusion reaction
Febrile non-hemolytic transfusion reaction
Bacterial sepsis or contamination
TRALI
Etiology unrelated to transfusion
35
AHTR
Accelerated clearance of red cells in a transfusion recipient due to immunologic
incompatibility between the blood donor and the recipient
Antigen-positive red cells are transfused to a recipient who has incompatible
allo-antibodies
Results in intravascular hemolysis
Generally within the top 3 causes of transfusion-related mortality
Often due to the administration of ABO incompatible blood
– cross-match error
– wrong identification of blood specimen
– blood administered to wrong patient
May rarely be due to recipient allo-antibodies to other red cell antigens
36
AHTR continued
Acute onset : often within first 15 minute of starting transfusion (as little as 2030 ml)
Initial presentation: fever, chills, anxiety, nausea, vomiting, pain (flank,
abdomen), dyspnea, hypotension, brown urine, bleeding
Complications: renal failure, DIC, death
Treatment:
– stop transfusion immediately
– begin infusion with normal saline
– alert blood bank, c heck for clerical error, sent entire transfusion set-up
for testing
Supportive care: monitor vital signs, maintain BP and urine output, monitor
for hyperkalemia, treat any resulting coagulopathy
37
Febrile Non-hemolytic
Transfusion Reaction
Common adverse event
– 1 in 10 transfusions of pooled random donor platelets
– 1 in 3000 units of RBCs
Frequency varies with:
– type of blood product
– age of blood product
– WBC content of blood product
– recipient characteristics
– ? pre-medication
– variability in recording of symptoms
38
FNHTR - continued
Etiology:
• reactions mediated by antibodies (recipient alloantibody reactive to antigens
on WBCs in component)
• reactions mediated by biologic response molecules
Clinical Presentation:
• Fever (>1°C rise) during or soon after transfusion (5 - 10% present 1-2
hours after transfusion)
• Chills and rigors
• Nausea and vomiting
Treatment:
• Stop the transfusion and assess patient
• Rule out other more serious causes (AHTR, bacterial contamination)
• Tylenol +/- Demerol
• continue transfusion cautiously
39
Bacterial Contamination
Component
Bacterial
Contamination
Symptomatic
Septic
Reactions
Fatal Bacterial
Sepsis
Platelet Pool
1 in 1,000
1 in 10,000
1 in 40,000
RBC (1 unit)
1 in 50,000
1 in 100,000
1 in 500,000
This is the most frequent infectious risk associated with transfusion
Accounts for about 11% of deaths due to blood components
Occurs most frequently with platelets
(Stored at 20 - 24° C -- excellent growth medium for bacteria)
40
Etiology
Blood components may be contaminated by:
• unrecognized bacteremia in the donor (ex Yersinia
enterocolitica)
• skin organisms from the donor (ex staphylococcus
epidermidis)
– difficult to totally decontaminate surface of skin
– small core of skin may enter phlebotomy needle at
time of donation
• contamination from the environment or handling of the
product (ex Serratia marcescens)
– leaky seals, damaged tubing, etc.
41
Commonly Implicated Bacteria
Gram-negative:
Gram-positive:
• Klebsiella pneumoniae
• Staphylococcus aureus
• Serratia marcescens
• Staphylococcus epidermidis
• Pseudomonas species
• Bacillus cereus
• Yersinia enterocolitica
42
Clinical Presentation
Depends on bacterial load and species of bacteria
•
•
•
•
•
•
rigors, fever, chills
hypotension
tachycardia
nausea and vomiting
dyspnea
DIC
Usually occurs during transfusion of the implicated product
43
Management and Investigation
• Stop the transfusion immediately
• Notify the hospital blood bank
• Return residual product and tubing to blood
bank
• Collect peripheral blood samples for culture
• Aggressive supportive therapy
• Broad spectrum therapy
44
Differential Diagnosis of a
Transfusion Reaction with Fever
Febrile non-hemolytic transfusion reaction
– usually temp < 39° C
– during transfusion; usually towards the end
Bacterial contamination
–
–
hypotension, shock, DIC
usually within first 15 minutes of a transfusion
AHTR
•
•
flank pain, DIC, hypotension
usually within first 15 minutes of transfusion
TRALI
–
–
SOB, hypoxemia, hypotension
within 6 hours of transfusion (usually during)
45
Allergic Reaction
Usually due to soluble allergenic substances in the plasma
of donated blood
– react with pre-existing IgE antibodies in the recipient
– causes release of histamine from mast cells and basophils
Possible mechanisms
– pre-existing anti-IgA in IgA-deficient patient
– pre-existing antibodies to other serum protein that patient is
lacking (IgG, Albumin, haptoglobin, alpha1-antitrypsin,
transferrin, C3, C4, etc.)
– passive transfer of IgE antibodies
– transfusion of allergen to which patient is sensitized to (drugs,
chemicals)
46
Incidence:
• mild 1:33 – 1:100 (1-3%)
• severe 1:20,000 - 1:47000
Timing
• during transfusion, or up to 3 hours from
the start of presentation
47
Signs and Symptoms
•
•
•
•
•
•
•
•
•
•
hives
pruritis
angioedema
cough and wheezing
nausea and vomiting
abdominal pain
diarrhea
hypotension
cyanosis
tachycardia
48
Signs & Symptoms of
Serious Reactions
•
•
•
•
•
•
•
hypotension/shock
shortness of breath, hypoxemia
cough
tachycardia
nausea and vomiting
generalized flushing or aniety
widespread rash (>2/3 of body)
49
Management
Non-serious:
• antihistamine
- diphenhydramine 25-50 mg PO/IV
• continue transfusion with caution
• stop transfusion if any "serious" symptoms
Serious:
• stop transfusion and do not restart
• notify hospital transfusion service
• epinephrine
• antihistamine
• corticosteroids
• supportive therapy as required
50
Summary
Initial management of transfusion reaction
–
–
–
–
–
stop transfusion immediately
notify blood bank
maintain IV access
monitor patient's vital signs
recheck identification of patient
Assess for symptoms of "serious" reaction
51
What actions does Canadian
Blood Services take when
these are reported?
Immediate:
• assess need for companion component recall
• assess need for in-date component recall from same donor
• assess need for hospital notification about potential component
problem
Next step:
• assess need for additional product testing
• assess need for lot number investigation
Possibly:
• assess need for donor notification, testing, deferral
52
Health Canada Reporting
• tracking trending...
53
TACO
This is an iatrogenic clinical issue, and not a
product problem.
However, we continue to receive these
reports. (frequently because there is an
uncertainty as to whether or not it is TRALI)
54
ABO incompatibility
Health Canada does not require this
information from CBS. (Provided labelling is
correct!)
55
TTISS
(Transfusion Transmission
Injuries Surveillance System)
• Public Health Agency of Canada
• Electronic reporting from hospitals directly to PHAC
• Most, but not all hospitals, are providing this information
• DOES include reports of "wrong unit to wrong patient"
• Reconciliation of reports with CBS and Héma-Québec
• Last annual Program Report printed 2004/2005 (is available online)
56
Plasma Protein Products
• Direct reporting from hospitals to Health Canada
(CBS may, or may not be in the loop)
• This includes both patient reactions, as well as product
complaints
• The manufacturer investigates, and sends CBS the
report (… I send a copy to the relevant hospital).
• Also extremely useful for trending.
(example - hemolysis associated with IVIg)
57
What about current infectious
disease risk?
O’Brien SF, Yi Q-L, Fan W, Scalia V, Fearon MA, Allain J-P. Current
incidence and residual risk of HIV, HBV and HCV at Canadian Blood
Services. Vox Sang. 2012;103:83-6.
Incident rates estimated for allogeneic whole blood donations 20062009 . Based on transmissible disease conversions of repeat
donations with a 3-year period.
Residual risk of:
HIV
1 per 8 million donations
HCV 1 per 6.7 million donations
HBV
1 per 1.7 million donations
58
Adverse Reactions
Analysis:
•
•
There were 130 ARs reported from September 2009 to September 2010; none were related to an error by
CBS.
There were 10 ARs reported in September 2010, within the statistical range of 4 to 16.
Results:
ARs by Category
The column chart to the left, ARs by Category, illustrates the ARs as
categories based on the type of reaction. The 5 most prevalent/noteworthy
are bar graphed.
20
15
10
5
Potential product problem
Se
p10
Ju
l-1
0
Au
g10
Ju
n10
M
ay
-1
0
Ap
r-1
0
M
ar
-1
0
Fe
b10
Ja
n10
De
c09
No
v09
Se
p09
O
ct09
0
Known complication
Sep-09
Most prevelant ARs reported to Health Canada
Oct-09
7
Nov-09
Dec-09
6
Jan-10
Feb-10
5
1. Known Complication of transfusion (e.g. allergic,
anaphylactic, febrile, PTP, acute/delayed hemolytic). 7 of these
were reported to HC in September 2010.
•
2 Allergic
•
1 TACO
•
1 PTP
•
1 Febrile
•
2 Miscellaneous
2. Potential Product Problem of transfusion (e.g. TRALI,
bacterial sepsis, transfusion transmitted WNV). There were 2
suspected TRALI reactions and 1 suspected Bacterial reaction
reported to HC in September 2010.
TRALI suspected
•
1 RBC (male)
•
1 FFPA (male)
Bacterial Suspected
•
Patient and 1 unit positive for gram negative bacilli
Mar-10
Apr-10
May-10
4
Jun-10
ARs, Cumulative 13 months: n = 130
2%
Suspected TRALI (39)
2%
Febrile (23)
13%
Jul-10
3
Aug-10
Sep-10
TACO (19)
29%
5%
Allergic (8)
5%
2
Anaphylactic (6)
6%
Delayed Hemolytic (6)
1
Acute Hemolytic (2)
6%
15%
0
Suspected TRALI
Allergic
Febrile
59
TACO
Suspected Bacterial
Suspected Bacterial (8)
17%
PTP (2)
Miscellaneous (17)
60
61
62
63
64
65
66
? QUESTIONS ?
? SUGGESTIONS ?
67