Download Blood Transfusion - The Ontario Transfusion Coordinators (ONTraC

ONTraC presentation
Plus random slides after
(28 MB)
Note: this presentation
contains custom animation
and with some slides you need
to wait until this takes effect
With particular thanks to Dr James Isbister of Sydney, Australia
1
Blood Transfusion:
An expensive & potentially
hazardous alternative to
Blood Management
John Freedman
Director, Transfusion Medicine
St Michael’s Hospital
University of Toronto
2
As Henry VIII said to each of his 6 wives3
Objectives of this presentation
To gain an understanding of:
Risks of allogeneic transfusion
Infectious
Immunologic (TRALI, immunomodulation)
Errors
Blood conservation/transfusion alternatives
An Ontario approach to blood conservation
4
Blood will immerse you in a world
of horror unlike any you've
experienced before. Brace
yourself for a nightmarish battle
against the bloodthirsty minions
of an ancient, forgotten god bent
on wiping humanityWith
from
the face
thanks to
Dr James Isbister, Sydney, SABM 20055
of the earth
‫כי נפש הבשר בדם הוא‬
Leviticus 17
(‘the life/soul of the flesh is in the blood’)
‫ויקרא‬
Blood transfusion: other than
as a scarce and expensive resource, who cares?
1:18,000 units to wrong pt
6
Blood
transfusion
Patients think blood transfusion
is special and beneficial, but have
difficulty accepting small risks
they can’t control.
Blood Donors believe their
contribution is a gift to the
community that will be used
appropriately and safely
Clinicians think blood is ordinary,
take blood transfusion for
granted, benefit is assumed and
risks regarded as minimal.
Governments view blood as a
commodity and transfusion
medicine as an expensive
support service which should be
regulated and funded in a cost-7
effective manner.
8
• 1997 Krever Commission: Recommendation #9:
“It is recommended that ….. promote appropriate
use of, and alternatives to, blood components and
blood products.”
• 1996 Gallup Poll indicates that only 7% of respondents
would want to receive donated blood; 82% think patients
should have the right to make final decision
9
Virus TTI
Residual risk
HIV
HCV
Per unit
Risk of death from:
(actuarial tables)
1:10 million
1:3 million
MVA
1: 9,000
Home accident
1: 10,000
Murdered in Canada 1: 85,000
HBV
1:72,000 (no NAT)
General anaesthesia 1: 20-50,000
Lightning
1: 3,000,000
HTLV 1:1.1 million
Chiavetta et al, CMAJ, 169:67-73, 2003
10
Bacterial contamination
Standard collection pouch
bacterial
bacterial febrile
severe fatality
contamination survival in reaction reaction 106
component
105
4
10
103
12
10
Log CFU/ml
102
8
6
4
2
0
1
2
3
SkinDays
fragment
of storage
4
5
11
Bacterial contamination of platelets
N
Blajchman (1995) 15,838
plt type
RDP
% positive
0.04%
Risk of receiving BCP 50-250-fold > combined risk from virus TTI.
Estimated that BCP kill ≈15 Canadians/yr
12
The BSE threat, vCJD & transfusion
UK
13
vCJD (variant Creutzfeldt-Jakob)
First case in UK in 1996; annual increase; ? peaked
167 cases of vCJD worldwide; 1 in Canada
Human cases about 5 yrs after BSE epidemic
Growth hormone, corneas, ---
?No transfusion-transmitted cases
Currently no screening test for vCJD
Geographic exclusion criteria
for
donor
exclusion
1994
Llewelyn et al: Lancet 363:417-421, 2004
Peden et al: Lancet 364:527-529, 2004
2003
14
TRALI:
Transfusion-related acute lung injury
leading cause of transfusion-related death
Anti-leukocyte antibody, usually in the donor blood product
15
TRALI cases: Canada
20
01
20
02
20
03
20
04
20
05
80
70
60
50
40
30
20
10
0
19
98
-2
00
0
Number of cases
TRALI cases per year
• Age – median 68 years, range 16-94 years
• Sex – female 45%, male 55%
• Blood pressure – 30% hypotension, 24% hypertension,
•
75% perioperative (CVS), haem/onc, trauma patients
16
TRALI:
New acute lung injury; bilateral pulmonary infiltrates
• Within 6 hours of plasma-containing transfusion
• Acute respiratory distress
. ● Hypoxemia
PaO2 of 30 – 50 torr;
PaO2/FIO2 <300 mm Hg;
O2 saturation < 90% on room air
• Fever
(1 to 2 oC)
• No evidence of circulatory overload
17
TRALI:
often difficult to know if X-ray image that of noncardiogenic pulmonary edema
• Rales and diminished breath sounds
• Normal jugular venous pressure
• Normal/low pulmonary wedge pressure
• Does not respond to diuretics
• Hypotension does not respond to intravenous fluids
• Absent S3
18
TRALI patients
• 17% died
• 48% mechanical ventilation (70% of those who died)
• Donor α-leukocyte antibodies in 63%
α-PMN in 54% of those who died vs in 25% of patients who recovered;
sicker patients also frequently received components containing α-HLA,
particularly class II
19
Donors
• 9 % of donors had anti-PMN
(equal frequency female & male)
percent
• Overall, 18 % of donors had anti-HLA Frequency of antibodies in donors
(29% female vs 7% male)
30
Females
Males
25
20
15
10
5
as
s
cl
LA
I
cl
a
cl ss
II
as
s
I+
 II
-P
M
N
• ?? Remove female blood donors
0

-H
• ?? Remove suspect donors from
the donor pool;
• Many donors implicated had donated
many times before (in one case >200
times) without a previously reported
TRALI reaction
20
Donor blood products with α-leukocyte antibodies
implicated in TRALI cases
Product transfused
Percentage
Packed red blood cells
31 %
Random donor platelets
29 %
Fresh frozen plasma
18 %
Whole blood
4%
Apheresis platelets
3%
Cryosupernatant plasma
1%
Cryoprecipitate
1%
Not reported
13 %
21
Antibody to WBC
TRALI
Ag/Ab reaction
C’ activation
Pulmonary damage
Capillary leak syndrome
Pulmonary endothelial damage
Leukosequestration
Pulmonary endothelium
primed PMN sequester on EC, adhere, cytoskeletal
change, rigid, trapped in microvasculature
Immunogenic
Classical theory, anti-leukocyte antibody,
ActivationTRALI:
of EC
but antibody not
always found.
Hyper-reactive PMN
chemokines
adhesion molecules
Silliman et al: Non-immunogenic TRALI. 2 stage process.
Release enzymes
PMN
primed
i. Susceptible
patient: sepsis, surgery,
trauma,
Transfusion:
2
Susceptible patient
1
ii. Transfusion BRMs:
• Sepsis
• Surgery (CPB)
• Trauma
• Lipids (Lyso-PCs)
• Cytokines
• Antibodies
22
1 Susceptible pt: sepsis,
surgery, trauma
2 Transfusion (BRM)
Lipids (lyso-PCs)
Cytokines
(antibodies, microvesicles, cell fragments)
Activated EC
 Chemokines
Adhesion molecules on EC
Attraction Tethering Firm Adhesion
Activation EC damage
Primed
PMN
Rigid
Pulmonary endothelium
Trapped
. in mv
Hyperreactive
enzymes
O2-
Capillary
leak
TRALI
Lung damage
23
Transfusion-induced immunomodulation
Renal allograft survival [Opelz & Terasaki, 1981]
Graft one year survival rates
23% in patients not transfused
87% in patients receiving > 10 transfusions
transfusion-induced immunosuppression (allogeneic leukocytes)
24
Transfusion-induced immunomodulation
(due to allogeneic leukocytes)
Some potential mechanisms:
•
Clonal deletion or anergy (of CTLs)
•
Induction of suppressor cells
•
Production of antiidiotypic antibody
•
Suppression of NK cell activity
•
Polarization of cytokine response
25
Infections & perioperative transfusion
10/16 observational studies and 4/5 randomized
trials showed statistically significant reduction in
postoperative infections with autologous versus
allogeneic transfusions.
Even more true for no transfusion versus allogeneic transfusion
26
In various surgical settings, no variable was more
consistently associated with postoperative infection
than was perioperative allogeneic transfusion

For each allogeneic RBC unit given, 1.5
fold increase in nosocomial infection.

Translates into potential morbidity,
mortality and LOS.
(Koval et al, J Orthop Trauma, 1997, 11:260)
27
SHOT, UK, annual report 2000-01
Adverse effects of transfusion
TRALI
4.8%
TRALI (15)
4.8%
TA-GVHD
(1) 0.3%
TA-GvHD
0.3%
PTP (3) 1.0%
PTP
1.0%
TTI 1.9%
TTI (6) 1.9%
DTR (40) 12.7%
Delayed HTR 12.7%
ATR (37) 11.7%
Acute HTR
11.7%
IBCT 67.6%
IBCT (213) 67.6%
Incorrect blood component transfused (IBCT):
“Wrong blood” is, without exception, an
avoidable error
28
SHOT 1996/97 to 2001/01
•
•
•
•
•
•
Blood centre
Transfusion laboratory
.
Collection, administration
Prescription, sampling, request
Other
Unknown
2%
28%
55%
Wards
68%
13%
1%
<1%
29
30
Cost of Blood Transfusion (in US$, 1998)
Mean Overall Cost: $491-$545 per unit.
Overhead
46%
Variable Direct
Labour 17%
Direct
Material
19%
Fixed Direct
Labour 18%
• Overhead = facility cost
• Variable direct labour = lab technologists,
phlebotomists, nurses
• Fixed direct labour = administrators, etc.
• Direct material = supplies, blood, tests
Ontario blood budget:
$420 million per year
.
Cremieux P-Y, Barrett B, Anderson K, Slavin MB. J Clin Oncol 18:2755, 2000
31
Costs incurred in provision of blood
•
•
•
•
•
•
•
Recruitment and collections
Infectious disease testing
Manufacturing, shipping, handling, labelling
Pre-transfusion testing
Transfusion costs
Post-transfusion sequelae
Regulatory and legal costs
32
Hospital charges
•
•
•
•
•
•
•
•
•
•
Blood type ABO
$
Blood type Rh
Antibody screen
Crossmatch, immediate spin
Crossmatch, antiglobulin (Coombs)
Red cell antigen screening, per antigen
Fresh frozen plasma thawing
Crypoprecipitate pooling
Handling
Surcharge
156
85
182
350
391
108
156
43
86
15%
Zeger, Jabbour (USC): Transfusion-free medicine and surgery, 2005, Blackwell
33
COSTS: Adult open heart surgery
Product
Number Product
Hospital
Total ($)
fee/unit ($) fee/unit ($)
Red cells
6
276
477
4520
FFP
5
53
250
1515
Platelets
1
500
200
1400
ABO type
1
156
185
Rh type
1
85
85
Antibody
screen
Total
1
182
182
$ 7,887
34
Jabbour, 2005
It is clear that:
1) the demand for blood
outweighs the supply
2) there are real risks associated
with blood transfusion
3) blood is not ‘free’
35
Blood transfusion is a lot like marriage.
It should not be entered into lightly,
unadvisedly or wantonly,
or more often
than is absolutely necessary.
[Beal RW: Aust N Z J Surg 46:309, 1976]
36
Blood is Good?????
37
1960
1971
38
Blood
 Enough
 In the right place
 At the right time
 And not too much
Most people in this room will depart
Earth as a result of not maintaining one
or more of these functions of the blood
J Isbister, SABM 2005
39
40
Blood Conservation:
Management Aims
• Allogeneic transfusion avoidance
• Transfusion reduction
41
Goals: Minimize Anemia and Avoid
Allogeneic Blood Transfusion.
Risk
Anemia
(Reduced
Hematocrit)
Allogeneic
Transfusion
Transfusion has risks,
but bleeding to death is fatal !
42
Anemia is common: 30% patients preop
In the ICU, most patients anemic at time of admission.
Hb typically declines by at least 0.5 g/dL/day in first 3 d
of ICU stay. Continues to decline if sepsis/severe illness.
These patients particularly may be at risk from anemia
(cardiovascular, respiratory, metabolic compromise).
Etiology of anemia multifactorial:
phlebotomy, GI bleeding, coagulopathy, blood loss from
vascular procedures, renal failure, nutritional deficiencies,
marrow suppression, impaired erythropoietin response, etc
43
Office of the
Director of Medical
Services
Blood
Conservation?
?
“I need you to find a radically innovative
new way to keep everything exactly the
44
same”
Blood conservation approaches in surgery
Autologous blood (PAD, cell salvage, ANH)
Erythropoietin (EPO, Eprex)
Other pharmacologics (e.g. antifibrinolytics)
Fibrin glues (e.g. Tisseel)
Hemostatic/harmonic scalpels
Blood substitutes
Controlled hypotension; positioning
Minimally invasive surgery
Transfusion trigger (level of Hb)
rFVIIa
etc
45
Is blood conservation approach effective
in avoiding allogeneic transfusion?
Preoperative Autologous Donation (PAD) in
primary hip surgery:
No PAD,
PAD,
29% had allogeneic transfusion
6% had allogeneic transfusion
(B Feagan; 2001/2002); 28 Ontario sites; 3352 pts
46
Pre-operative EPO for Orthopaedic Surgery
Feagan BG et al. Ann Intern Med 133:845-854, 2000.
Allogeneic Blood Transfusions
45% in placebo group
23% in low dose EPO (p<0.003)
11% in high dose EPO (p< 0.001)
Significant requirement for supplemental iron
Monitor serum ferritin, transferrin saturation
47
Initial Hb level predictive of transfusion.
BC Capital Health Region
Hb pre-op
% transfused
< 130
53 %
> 130
20 %
But, if
Hb done in PAF EPO
15%
< 130
Iron
> 130
5%
B12, folate
48
Transfusion trigger: How much Hb do you need?
Operative mortality increases with untreated anemia.
Preop Hb
Mortality
< 60 g/L
62%
61 - 80
33%
81 - 100
0%
> 100
7%
Carson, Am J Surg 170:6A:32S, 1995
Adjusting for APACHE II score: Post-op, 2.5X increase in odds of
death for each 10 g/L decrease in Hb below 80 g/L
(Carson et al: Transfusion 42:812, 2002)
49
Crude in-hospital survival rate of patients with different preoperative haemoglobin concentrations
.
Preoperative haemoglobin >100g/L
.
Preoperative haemoglobin ≤100g/L
So level of Hgb important, but at what
trigger should one transfuse?
.
Lancet, Vol 369, May 18, 2002
50
So how many red cells do you need?
“The bad news is, you have only one red blood cell.
The good news is, he’s a workaholic!” 51
Hébert et al; NEJM 340:409, 1999: ICU patients (TRICC)
Transfusion trigger randomized by Hb (70
vs 100 g/L)
restrictive liberal
Units transfused
2.6
5.4
Mean Hb values
85
107
Hospital morbidity
22%
28%
ICU mortality
14%
16%
30 day mortality
19%
23%
Organ failure score
8.3
8.8
Trend to improved survival in restricted group (p=0.10)
52
Transfusion
trigger
1940’s – 80’s: Hb 100g/L
1980’s – 2005: Hb
80g/L
70g/L
60g/L
53
WHAT HGB LEVEL?
• SAFE PREOPERATIVE
HGB WILL VARY FROM
ONE PATIENT TO THE
NEXT, AND
• SAFE PREOPERATIVE
HGB WILL VARY FOR
THE SAME PATIENT
DEPENDING ON
CLINICAL
CIRCUMSTANCES
54
When Does Anemic Organ Injury Occur?
Tissue
Hypoxia
30 g.L-1
Clinical Evidence
Of Harm
70 g.L-1
Activation of
Protective Mechanisms
90 g.L-1
100 g.L-1
Hemoglobin Concentration
55
What is the Optimal Transfusion Threshold ?
Anaerobic
Metabolism
No CoMorbidities
?
30 g.L-1
70 g.L-1
CoMorbidities
???
90 g.L-1
100 g.L-1
Hemoglobin Concentration
56
.
Hb decrease 2 – 3.9 g/dL
Hb decrease > 4 g/dL
Hb decrease 2-3.9 g/dL + CVD
.
.
Adjusted odds ratio for mortality according to preoperative hemoglobin
concentration in patients refusing red blood cell (RBC) transfusions.
While cardiovascular disease (CVD) increases the risk of mortality,
increased blood loss during surgery (resulting in a decrease in Hb) are
also associated with an important rise in the risk of death.
Adapted from Carson JL et al. Lancet 348: 1055, 1996.
57
Blood Management
is all about
 Oxygen
 Hemostasis
58
Arsenal FC
Tour de France
J Isbister, SABM 2005
59
Modified from James Isbister, SABM 2005
Red Cell
& Hb Function
O2 Consumption
Inspired PO2
Lung Fn
(Diffusion)
Cardiac &
Vascular Fn
HbO2
O2 Delivery DO2
Red Cell, Hb
Endothelial Fn
HbO2
Interstitial
Space
Hemoglobin
O
O2
Tissue
Metabolism
2
O
Hemoglobin
O2
2
Myoglobin
HbO2
O2
ATP
CO2
60
With thanks to James Isbister, SABM 2005 (modified)
Limit transfusion to appropriate need. Transfuse unit by unit.
There is no single Hb value optimal for all patients:
•
•
•
•
Assessing
Efficacy
consider
factors
such as:
Cardiac output
Red cell survival
Heart rate, stroke volume, contractility
Hemoglobin
level resistance
Peripheral vascular
Increased
O2 release from red cell
Patient
symptoms
Decreased blood viscosity
Doctor
feels better
Dilution
61
DEVELOPING A NETWORK of
ONTARIO TRANSFUSION COORDINATORS
MOH
 Enhance transfusion practice outside of the Blood Bank
* ‘clinical bridge’ between Transfusion Service & rest of hospital
 Interact with physicians, nurses & patients to promote
blood conservation & alternatives to allogeneic transfusion
.
Anticipated a 5 to 10%
reduction in red cell use
.
Susan Gagne; Niagara Health System; 905-684-7271 ext 46570
62
Pre-operative approach
assess at pre-admission clinic (3-5 weeks before surgery)
identify patients at risk of transfusion ahead of surgery
discuss informed consent and transfusion alternatives
investigate, diagnose and treat anemia
(family doctor, surgeon, anesthetist, hematologist)
erythropoietin and / or iron
predonation of autologous blood (with hematinics + EPO)
stop anticoagulants/antiplatelet drugs if safe to do so
minimize blood taken for lab testing
63
Progress
23 hospitals chosen based on blood utilization & geography
• At specific time periods, collect detailed anonymized patient
information for a defined number of all consecutive patients
admitted for the designated procedures
• Evaluations: Baseline (Jan 2002), 12, 18 & 24 months
10
• Aggregate data for Ministry of Health of Ontario;
Site-specific
data for each institution
10
HSC, MSH, UHN, TEGH, SJH, SWCHC, SMH, BrH, Tr,
[Guelph General Hospital, Hamilton Health Sciences Centre, Hospital for Sick Children (Toronto), Kingston
General Hospital, Lakeridge Health (Oshawa), London Health Science Centre, Mt Sinai Hospital (Toronto),
Niagara Health System, North Bay General Hospital, Peterborough Regional Health Centre, Sault Area
Hospitals (Sault St Marie), Scarborough General Hospital, St Joseph’s Health Centre (Toronto), St Mary’s
General Hospital (Kitchener), St Michael’s Hospital (Toronto), Sudbury Regional Hospital, Sunnybrook &
Women’s College Health Sciences Centre (Toronto), The Ottawa Hospital, Toronto East General Hospital,
Trillium Health Centre (Mississauga), University Health Network (Toronto), Windsor Regional Hospital]
64
80
60
White = pre-ONTraC
Blue = at 6 mos
Yellow = at 16 mos
Red = at 24 mos
40
20
itt
e
e
m
itt
e
co
m
m
co
ns
oo
d
bl
Tr
an
s
fu
s
er
v
io
at
n
n
co
m
co
ed
rm
in
fo
e
0
ns
en
t
Percentage of hospitals
100
Education in-services in
previous 6 mos:
Pre-Ontrac
At 6 mos
At 16 mos
At 24 mos
= < 20
= > 140
= > 250
= > 290
65
Three targeted surgical procedures
Knee arthroplasty:
19 hospitals; 1150 patients at each time point
AAA surgery:
17 hospitals; 300 patients at each time point
CABG surgery (primary):
4 hospitals; 300 patients at each time point
66
Proportion of knee surgery patients (N=1119)
who received allogeneic blood
100
BASELINE
Percent transfused
90
80
Mean for:
Bilateral
knees
70
60
50
Revision
knees
40
30
one knee
20
10
X
X
0
ALL 1
Aggr
2
3
4
5
6
7
X
8
X
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Site number
At baseline, marked variation across province
in likelihood of receiving a transfusion
44
67
% Allogeneic
%With Allogeneic %
Transfusion
Baseline vs 12 M onths,
by site
Baseline vs One
12Knee:months;
receiving
allogeneic
transfusion
100
Blue baseline
Red 12 months
80
60
One knee
40
20
0
All
All
1
2
3
4
5
6
8
9
10
11
12
14
15
16
17
18
19
20
21
22
Site Number
CABG
CABGs: % With Allogeneic Transfusion
urgent
100
90
80
70
60
50
40
30
20
10
0
elective
100
% Allogeneic
% Allo
AAAs: % With Allogeneic Transfusion
AAA
(Baseline vs 12 Months) by site
80
Baseline
60
Baseline
40
12 Month
12 Month
20
0
2
3
4
7
8
9
10 11 12 14 15 16 17 18 19 21 22 23
Site Number
All
All
4
7
18
23
Site Number
At 12 months, most, but not all, hospitals showed a reduction in the
5
68
proportion of patients transfused with allogeneic RCC
5
% Allogeneic
%With Allogeneic %
Transfusion
Baseline vs 12 M onths,
by site
Baseline vs One
12Knee:months;
receiving
allogeneic
transfusion
100
Blue baseline
Red 12 months
80
60
One knee
40
20
0
All
All
1
2
3
4
5
6
8
9
10
11
12
14
15
16
17
18
19
20
21
22
Site Number
CABG
CABGs: % With Allogeneic Transfusion
urgent
100
90
80
70
60
50
40
30
20
10
0
elective
100
% Allogeneic
% Allo
AAAs: % With Allogeneic Transfusion
AAA
(Baseline vs 12 Months) by site
80
Baseline
60
Baseline
40
12 Month
12 Month
20
0
2
3
4
7
8
9
10 11 12 14 15 16 17 18 19 21 22 23
Site Number
All
All
4
7
18
23
Site Number
At 12 months, most, but not all, hospitals showed a reduction in the
5
69
proportion of patients transfused with allogeneic RCC
5
60
55
50
45
40
35
30
25
20
15
10
5
0
Non-autologous pts
B
G
C
A
ee
kn
C
A
ee
B
G
baseline
12 mos
18 mos
24 mos
kn
percent
Percent transfused with allogeneic RCC
Autologous pts
70
Projected % reduction from baseline in allogeneic
RCC use for province for the 3 targeted procedures
RCC used 2003 vs 2002
At 12 mos
At 18 mos
40
RCC use 2003 vs 2002
2.0
percent change
percent reduction
2.5
30
20
10
1.5
1.0
0.5
0.0
-0.5
-1.0
-1.5
-2.0
-2.5
0
knee
CABG
AAA
other
provinces
Ontario
ONTraC
yes no
.
• Reduction in allogeneic transfusion markedly exceeds the anticipated 5-10%
• Historically, Ontario had the highest annual rate of increase in RCC use;
• 2003, Ontario had lower increase (net decrease) in RCC use than other provinces;
10
• ONTraC hospitals had lower increase in RCC use than non-ONTraC hospitals
71
Projected % reduction from baseline in allogeneic
RCC use for province for the 3 targeted procedures
Ontario Compared to Canada
RCC used 2003 vs 2002
At 12 mos
percent reduction
40
At 18 mos
RCC use 2003 vs 2002
Fresh Component Use
Ontario Compared to the Rest of Canada
2.5
2.0
percent change
850,000
30
800,000
750,000
700,000
650,00020
600,000
550,000
500,00010
1999/2000
2000/2001
2001/2002
All Canada (except QC & ON)
0
knee
CABG
2002/2003
Ontario
2003/2004
1.5
1.0
0.5
0.0
-0.5
-1.0
other
provinces
-1.5
-2.0
-2.5
Ontario
ONTraC
yes no
AAA
• Reduction in allogeneic transfusion markedly exceeds the anticipated 5-10%
• Historically, Ontario had the highest annual rate of increase in RCC use;
• 2003, Ontario had lower increase (net decrease) in RCC use than other provinces;
10
72
• ONTraC hospitals had lower increase in RCC use than non-ONTraC hospitals
Red Cells
Red Cells Issues - Ontario Compared to Rest of Canada (excl. QC)
(per 1,000 population) 1999-2000 to 2005-2006
36.0
34.0
32.0
30.0
28.0
26.0
24.0
1999/2000
2000/2001
2001/2002
Canada (except ON & QC)
2002/2003
2003/2004
2004/2005
2005/2006
Ontario
73
16
Transfusion-induced immunomodulation:
infection rate
14
Infection defined by
symptoms + pos culture
12
%
10
8
Allogeneic
6
No Tx
4
2
0
1
2
Knee
AAA
3
CABG
Rate of Infection (%)
Allogeneic
5.58
14.93
11.66
No Tx
2.25
5.33
5.44
p<.01
p<.001
p<.05
74
6
J Surg Research 2002;102:237-244
Prospective data from 6301 non-cardiac surgical procedures 1995-2000
Transfusion PRBCs > 4 units
Odds Ratio:
Death
2.84
Infection 9.28
P<0.001 for both
75
ALOS (mean + SEM) for no transfusion vs allogeneic transfusion
Average
length
stay (ALOS;
(ALOS; days)
SEM)
Average length
ofofstay
days)(mean
(mean
± SEM)
allogeneic transfusion
9
ALOS (mean + SEM) for no transfusion vs allogeneic transfusion
allogeneic
transfusion
knees
AAA
CABG
16
7 knees
14
6
8
5
7
8
6
4
3
2
4
1
2
0
ALOS(days)
10
9
ALOS(days)
ALOS(days)
8
12
no transfusion
6
allogeneic transfusion
no transfusion
*
knees
CABG
*
AAA
knees
*
no transfusion
AAA
knees
* AAA
*
CABG
*
knees
*
*
AAA *
CABG
*
CABG
*
*
*
*
*
AAA
CABG
*
*
*
5
4
3
2
1
0
0
baseline
12
months
baseline
1212
months
baseline
months
all comparisons
oftransfusion
no
transfusion
vsallogeneic
allogeneic transfusion,
P <PP
0.0001
*For
all
comparisons
no
transfusion
vs
allogeneic
transfusion,
<<0.0001
*For
all *For
comparisons
ofof
no
vs
transfusion,
0.0001
IN MULTIVARIATE ANALYSIS, ALLOGENEIC TRANSFUSION WAS AN
INDEPENDENT PREDICTOR FOR LOS
VARIABLES EVALUATED: Co-morbidities; Initial, pre-op, nadir & discharge hemoglobin levels;
Postoperative infection; Age; Sex; Number of units of blood transfused; Any blood conservation
7
76
measure (PAD, EPO, cell saver, controlled hypotension, fibrin glue, DDAVP, antifibrinolytics)
7
Average length of stay (ALOS; days) (mean + SEM)
one knee
8
6
4
No transfusion
Autologous
Allogeneic
2
m
os
18
m
os
12
e
se
lin
ba
m
os
18
m
os
12
e
se
lin
ba
m
os
18
m
os
12
se
lin
e
0
ba
ALOS (days)
10
77
Pre-op Hb versus number of units transfused
Pre-op Hb (g/L)
Pre-op
Pre-opHb
Hb
Mean Pre-op Hb
P < 0.0001
78
Compared to NO transfusion:
Knee
CABG AAA
Every ↓ in pre-op Hb of 10 g/L increases chance of allogeneic transf by 1.839 (84%) 1.847 1.433
Every ↓ in nadir Hb of 10 g/L increases chance of allogeneic transf by 4.31 (430%) 4.502 3.534
As age increases by 10 yrs, the odds of an allogeneic transfusion  by 1.515
As BSA decreases by -0.25, the odds of an allogeneic transfusion  by 1.466
Being female increases the odds of receiving allogeneic transfusion by 1.445
1.558 1.818
2.288 1.598
6.820 1.987
Having an allogeneic transfusion  odds of postoperative infection by
2.653
2.681 1.950
Each additional allogeneic unit  the chance of infection by a factor of
1.587
1.524 1.488
79
6
5.394
5
Odds Ratio
Compared to
having 0
Units
transfused
Increased risk of
4
3.54
3.205
3
2
2.963
2.395
2.323
1.79
1.338
1
2.258
1.721
1.524
1
2
3-5
6+
postoperative
infection per
allogeneic units
RCC transfused
1.312
One Knee
CABG
AAA
# of Allogeneic Units Transfused
2
1.8
Odds Ratio
Compared to
having 0
units
Transfused
1.6
1.4
1.2
1
1.513
1.475
1.364
1.338
1.214
1.102
One Knee
1.331
1.239
1.23
1.109
1.153
1.074
CABG
AAA
# of Allogeneic Units Transfused
1
2
3-5
6+
Increased risk
of LOS per
allogeneic
units RCC
transfused
80
At 12 months,
For Ontario, estimate for the 3 targeted procedures only:
• Red cell product (at $400/unit)
8,640,000
• Reduced LOS
5,300,000
• Reduced work in hospitals
Total savings per year:
650,000
$14,950,000
• In addition: greater patient satisfaction and safety
Cost of program per year:
$ 1,800,000
Expansion to other procedures & other conservation measures
should result in even greater savings
81
What’s best for the
blood supply?
What’s best for the
patient?
82
Formula for “Scientific” Medical Opinion
Years from graduation
V
Academic rank
(Professor =1 ,
Lecturer = 4)
=
4
G x
T
A
Distance from regular
patient contact
J Isbister, SABM, 2005
83
CLINICAL DECISION MAKING
Clinical Experience
Repeating one’s own
mistakes with
increasing confidence
over time
Evidence Based Medicine
Minimal variation in
clinical practice with
people perpetuating the
mistakes of others
Nothing is black and white, medicine is
practiced in the context of constant uncertainty
84
Law
Politics
Perception
Practice
Evidence
Science
J Isbister
85
Relace transfusion with
Thomas S. Kuhn
1922-1996
• Blood conservation =
• Bloodless medicine =
• Bloodless surgery =
• Blood management
86
Bloodless
Surgery
Ott DA, Cooley DA. Cardiovascular surgery in Jehovah's Witnesses. Report of
542 operations without blood transfusion. JAMA 238:1256-8, 1977.
Jehovah's Witnesses who require operation represent a challenge to the physician
because of the patients' refusal to accept blood transfusion. We report a 20-year
experience with a consecutive series of 542 Jehovah's Witness patients ranging in
age from 1 day to 89 years who underwent operation. Early mortality (within 30 days
after operation) was 9.4%. In 362 patients requiring temporary cardiopulmonary
bypass, early mortality was 10.7%. Mortality was 13.5% among 126 patients who had
single- or double-valve replacement. The only deaths among patients who had aortic
valve replacement or repair of a ventricular septal defect occurred in those who had
some serious complication before operation. Preoperative or postoperative anemia
was a contributing factor in 12 deaths, and loss of blood was the direct cause of three
87
deaths. Cardiovascular operations can be performed safely without blood transfusion.
88
• Blood transfusion is risk factor for:
– Mortality
– ICU admission
– ICU length of stay
– Hospital length of stay
89
Why “bloodless medicine”…?
There are many bloodless medicine programs …and the number
is growing. Even in remote areas of Siberia, physicians and
patients know about bloodless medicine.
If one types “bloodless medicine” into an internet search engine,
> 12,000 hits are obtained.…
[from T Kickler, Johns Hopkins,
Transfusion 43:550, May 2003]
90
Bloodless medicine (or blood conservation)
Requires coordination of services across a variety of departments….
cooperation between outpatient scheduling, surgical and
anesthesia physicians and their clinic personnel, operating room
scheduling, intensivists and hematologists to get the patient
prepared, …the billing office….
This is in contrast to a transfusion, which can
usually be accomplished with one phone call….
[from T Kickler, Johns Hopkins,
Transfusion 43:550, May 2003]
91
Some institutions market their bloodless medicine programs by
pointing out the complications and adverse effects of allogeneic
transfusion, as a way to lower hospital expenses or length of hospital
admissions.
May be so, but careful outcomes research needed before making this
the only argument to establish bloodless medicine program.
The strongest argument for having a bloodless medicine program is to
respect the rights of patients…. based on the ethical value of autonomy
or self-determination, and medical institutions have a responsibility to
respond to this need.
A plethora of new techniques and therapies are available …and their
relative merits, alone and in combination, still needs to be investigated,
but it is becoming standard of practice.
92
3 year renewable contract signed; to 2009
5 new coordinators; 3 new sites
New targeted procedures
93
percent receiving allogeneic transfusion
Radical prostatectomy
Individual sites
40
35
30
25
20
15
mean
10
5
0
Aggr
94
Nadir hemoglobin levels as surrogate
measure of transfusion trigger
CABG: mean nadir Hb
90
85
85
70
65
60
60
no
n-
s
pa
t
to
lo
go
us
au
ut
ol
og
ou
no
na
au
to
lo
go
us
65
pa
ts
70
75
ou
s
75
80
to
lo
g
80
baseline
12 months
18 months
au
Hb (g/L)
90
s
Hb (g/L)
One knee: mean nadir Hb
Radical prostatectomy:
Non-autologous 83.29
Autologous
89.47
• Nadir hemoglobins higher for autologous than for allogeneic transfusions
• Progressive reduction in hemoglobin level trigger for transfusions
95
• Trigger hemoglobin higher in knee surgery than in CABG !!
9
Radical prostatectomy
(N=863)
50
percent
40
30
20
10
lle
%
au
to
un
its
%
pt
s
au
co
au
to
s
pt
%
to
co
tx
lle
ed
ct
ed
Tx
ed
ct
ed
al
lo
+
to
au
pt
s
%
%
pt
s
al
lo
tx
ed
0
20% of Pts had autologous blood collected, of whom 47% received their autologous blood; only 3.47%
also received allogeneic blood.
42% of autologous units collected were transfused.
96
Anesthesiologist
Cooordinator
Bureaucrat
ICU &
Wards
Opinion
Leader
Surgeon
Hematologist
Patient
Blood
Management
97
The best transfusion is
the transfusion not given!
Allogeneic blood transfusion should only be
used as therapy when there is evidence for
potential benefit, there are no alternatives, a
quality product is available and the risks are
appropriately considered and balanced against
the benefits.
☺
Thank you
98
99
Procedures employed:
PAD
EPO
Overall EPO use per month
baseline
12 months
18 months
15
10
5
50
40
30
20
10
20
04
03
nM
ay
20
Ja
M
ay
nJa
nD
Ja
ay
-D
ec
AAA
20
02
CABG
ec
knee
20
03
0
0
M
percent of patients
20
number patients per month
percent of patients undergoing PAD
• Increase in pre-operative autologous donation in CABG & AAA patients
100
• Progressive increase in use of erythropoietin after first year
11
Procedures
Utilized
(% of patients)
Other blood
conservation
procedures
(% of patients)
70%
60%
Cell saver
antifibrinolytics
Utilized
50%
40%
Baseline
30%
12 Months
20%
10%
0%
One
Kne e
AAA
CABG
One
Kne e
Ce ll Save r
AAA
CABG
Antifibr inolytics
Procedures Utilized
Pr oce dur e
10%
Fibrin glue
hypotension
DDAVP
% Utilized
8%
6%
Baseline
12 Months
4%
2%
0%
One
Kne e
AAA
CABG
Fibrin Glue
One
Kne e
AAA
CABG
Hypotension
One
Kne e
AAA
CABG
DDAVP
Pr oce dur e specific for type of surgery
Limited use of other procedures;
101
13
Miscellaneous slides
102
Pharmacologic agents: costs
»
•
•
•
•
•
•
•
Cost per dose
Eprex
Darbopoietin
Amicar
Aprotinin
DDAVP
Tranexamic acid
rFVIIa
588
132
18
540
Cost per course
2,350
530
46
1,000
144
73
7,056
Jabbour
(4.8 mg)
103
Transfusion trigger
Restrictive vs Liberal
104
105
106
107
Consider:
Hb > 130 g/L
PAD EPO cell saver

Hb >100 - <130 g/L
N/A

N/A
Surgery 2 to 4 weeks away


N/A
>10% likely to require transfusion



Anticipated blood loss (units)
1-2
1-5
>1;
>20% BV
Need for Fe supplement

Not within 72 h of surgery


108
Factors to consider in the surgical transfusion decision
Clinical history
Cardiopulmonary disease
Existing coagulopathy
Anemia
Trauma classification (mechanism of injury)
Medications
Antiplatelet drugs; Anticoagulants
Clinical symptoms
Dyspnea on exertion; Angina
Hemoglobin/hematocrit level
Oxygen delivery/consumption
Surgical procedure (elective vs emergency; laparoscopic vs open)
Estimated blood loss
Jehovah’s Witness
109
Independent predictors for transfusion:
Preoperative factors:
 Red blood cell mass
 Type of operation
 Urgency of operation
 Number of diseased vessels
 Serum creatinine > 1.3 mg/dL
 Preoperative prothrombin time
Postoperative factors:
 Cardiopulmonary bypass time
 Three or fewer bypass grafts
 Lesser volume of ANH removed
 Total crystalloid > 2500 ml
Moskowitz et al
110
Identifying patients for blood conservation strategies
24,509 consecutive adult surgical patients; 14 procedures (not neuro or cardiac)
• Type of procedure
• Age
• Sex
• Emergency surgery
• Preoperative autologous donation
• Preoperative hemoglobin level
Identifying patients for blood conservation strategies. Van Klei et al, Br J Surg 89:1176, 2002
111
Preoperative autologous donation (PAD)
Consider when:
 Preoperative hemoglobin >130 g/L
> 10% of patients undergoing procedure
require transfusion
 Elective surgery scheduled 2 to 4 weeks away
 Patient on iron supplement
 Not within 72 h of surgery
 no severe cardiovascular or hemodynamic problems
112
Autologous blood donation
Advantages
Disadvantages
Prevents transfusion-transmitted disease
No effect on risk of bacterial contamination
Prevents red cell alloimmunization
No effect on risk of ABO incompatibility error
Supplements the blood supply
Costs more than allogeneic blood?
Provides compatible blood for pts with alloabs Wastes blood not transfused
Prevents some adverse reactions
Possible adverse reactions from donation
Reduces likelihood of allogeneic transfusion
May subject patient to preoperative anemia
113
Autologous donation deferral
•
evidence of infection or bacteremia
• severe aortic stenosis
• unstable angina
• myocardial infarction or cerebrovascular accident in past 6 months
• high grade left main coronary artery disease
• cyanotic heart disease
• active seizure disorder
• uncontrolled hypertension
Br J Anaesth 78:768, 1997
114
PAD
observational
42 studies
RR 0.31
[Carless et al
Transf Med
14:123, 2004]
115
PAD
randomized
8 studies
RR 0.37
116
Autologous Donation:
In contrast to autologous blood donation under standard
conditions, in “aggressive” autologous blood phlebotomy
(twice weekly for 3 weeks beginning 25-35 days before surgery)
endogenous erythropoietin levels do increase.*
Can be further stimulated by exogenous erythropoietin.**
* Goodnough et al: J Lab Clin Med 236:57, 1995
**Goodnough et al: N Engl J Med 336:933, 1997
117
Erythropoietin
Consider when:
 Anticipated loss of two to five units
 Preoperative hemoglobin >100 to < 130 g/L
 Elective surgery scheduled 2 to 4 weeks away
 Patient on iron supplement
118
Different Formulations of Recombinant Erythropoietin
Estimated total number of cases of PRCA is about 250
Possibly related to formulation and increased incidence with sq administration
Never seen if EPO is administered IV
Since 1998- 1.7/10,000 cases in France, 0.26/10,000 cases in Germany
119
120
Percent patients transfused with allogeneic blood
CABG:
60
percent
50
40
30
.
20
10
.
gg
re
ga
te
N
il
-b
as
el
in
e
EP
O
al
on
e
PA
D
al
on
e
EP
O
+
PA
PA
D
D
+
C
ry
os
ea
l
0
O
nt
A
.
..
121
Cell Salvage
Consider when:
 Blood loss likely >20% of blood volume
 > 10% of patients undergoing procedure
require transfusion
 Mean transfusion requirement exceeds one unit
122
ANH
Consider when:
 Blood loss likely >20% of blood volume
 Preoperative hemoglobin >100 g/L
 Absence of severe cardiac disease
123
Before planned surgery:
• Assessment at preadmission clinic
• Correcting treatable anemia
• Stopping anticoagulants and antiplatelet drugs,
if safe to do so
• Erythropoietin and /or iron
• Pre-donation of blood, with hematinics + erythropoietin
• Minimizing blood taken for laboratory samples
124
During surgery:
• Losing less blood through optimal surgical &
anesthetic technique
• Keeping patient warm
• Using measured hematocrit or blood loss as guide to
red cell replacement
• Using rapid hemostasis testing to guide blood
component replacement
• Antifibrinolytics to reduce bleeding in selected cases
• Intraoperative cell salvage
125
After surgery:
• Postoperative cell salvage
• Using a protocol to trigger re-exploration at a specified
level of blood loss
• Use of a protocol to guide when hemoglobin should be
checked
• Use of a protocol stating blood transfusion thersholds
and targets
• Minimizing blood taken for laboratory samples
126
At surgery:
Meticulous dissection:
• Develop avascular planes
• Stop all small bleeders as encountered
Reduction of regional vascular pressure
• Appropriate patient position
• Blood inflow control
• Limb exsanguination & proximal tourniquet
Prevention of hypothermia
Optimal use of cell salvage127
“Haemostatic” dissecting instruments:
mechanism
disadvantages
Monopolar diathermy
heat transmission
collateral thermal damage;
most procedures
interferes with pacemakers;
ignition of flammable fluid/gas
Bipolar diathermy
heat
cannot “cut” tissues;
ignition flammable gas/fluid
Argon beam
heat
collateral thermal damage;
hepatobiliary
interferes with pacemakers; surgery
ignition of flammable gas/fluid
Laser (e.g. Nd-YAG, CO2)
heat
Ultrasound dissector
mechanical
cost
disruption; some heat
Water-jet dissectormechanical
as above
cost
applications
where need
precise dissection
according to laser
type
solid organ
surgery
solid organ surg
128
Key points:
surgical technique is most important determinant of
blood loss
simple physical methods result in significant reduction
in blood loss
minimally invasive surgery can contribute to blood
conservation
modern ‘haemostatic’ surgical instruments can
contribute to bloodless dissection, especially with
solid organ surgery
topical haemostatic agents, particularly fibrin sealants,
help when bleeding not controlled by more
straightforward means
129
Pharmacologics:
• High dose aprotinin reduces red cell and component
use in cardiac, hepatic transplant and major
orthopedic (but not vascular) surgery
• Tranexamic acid inconsistent in reduction of red cells
and no effect on component use
• Tranexamic acid no proven benefit in patients taking
antiplatelet drugs
• EACA does not reduce allogeneic transfusion
• DDAVP after cardiac surgery may be useful in proven
platelet dysfunction
• rFactor VIIa: await evidence from randomized
placebo-controlled studies
130
Potential difficulties:
• Clinical/diagnostic criteria not detailed enough
• Clinical information often missing/difficult to interpret
• Donor samples difficult to retrieve; donor recall delayed
• Shipping of samples: time, conditions
• Crossmatch samples availability rare
• Sensitivity of tests:
• inherent
• panel antigen coverage
• false positives and negatives
• technique specific
131
Factors to consider in the surgical transfusion decision
Clinical history
Cardiopulmonary disease
Existing coagulopathy
Anemia
Trauma classification (mechanism of injury)
Medications
Antiplatelet drugs; Anticoagulants
Clinical symptoms
Dyspnea on exertion; Angina
Hemoglobin/hematocrit level
Oxygen delivery/consumption
Surgical procedure (elective vs emergency; laparoscopic vs open)
Estimated blood loss
Jehovah’s Witness
132
Identifying patients for blood conservation strategies
24,509 consecutive adult surgical patients; 14 procedures (not neuro or cardiac)
• Type of procedure
• Age
• Sex
• Emergency surgery
• Preoperative autologous donation
• Preoperative hemoglobin level
Identifying patients for blood conservation strategies. Van Klei et al, Br J Surg 89:1176, 2002
133
134
K Sazama, Vox Sang 92:95-102, 2007.
K Sazama, Vox Sang 92:95-102, 2007.
135
136
Van der Linden P, Dierick A: Vox Sang 92:103-112, 2007.
137
Van der Linden P, Dierick A: Vox Sang 92:103-112, 2007.
138
Van der Linden P, Dierick A: Vox Sang 92:103-112, 2007.
139
140
141
142