Transcript History of Transfusion Medicine in Canada

Donald M. Arnold, MDCM MSc
Program Director, Transfusion Medicine
McMaster University
Canadian Blood Services
Disclosures
Speaker’s Topic:
“Viruses and Vampires: The History of Transfusion Medicine in
Canada”
(D. Arnold)
Financial Conflicts of Interest:
Research funding from CBS
Non-Financial Conflicts of Interest:
Associate Medical Director CBS
Unlabelled/ unapproved Use Disclosure:
N/A
The Past:
“Tainted blood scandal”
The Present: What we learned
The Future:
Where is TM headed
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Blood is a life-saving commodity
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Transfusion Medicine crosses all disciplines
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There will always be new threats to the blood supply
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People will continue to be harmed by blood
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Highly emotional, political business
Justice Horace Krever, 1997
“The most influential report on
public health in Canadian history”
-K. Wilson CMAJ 2007
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1,000 infected with HIV
30,000 infected with hepatitis C
After being transfused blood between late
1970s and 1980s
“Arguably the largest public heath
catastrophe in the country’s history”
-Picard, A. The Gift of Death 1995
“Would it not be possible, in time of peace and quiet, to form relief
societies for the purpose of having care given to the wounded in
wartime by zealous, devoted, and thoroughly qualified volunteers?”
Henry Dunant, founder of the Red Cross in 1863
1981:
First published report of homosexual men in the US
infected with PCP pneumonia
1982:
First reported case of PCP in patients with
hemophilia
1983:
593 people diagnosed with AIDS in the US
1983:
US blood bankers defer high risk donors
May 1984: HIV virus isolated (Robert Gallo)
Mar 1985: HIV test implemented in US
Nov 1985: HIV test implemented in Canada
1986: US implements ALT surrogate testing for NANB
hepatitis
1990: Test for hepatitis C implemented
1993: Results of the Blajchman-Feinman study presented
1995: Study results published (Lancet)
1997: The Commission of Inquiry on the Blood System in
Canada (“Krever Commission”) released
1998: Birth of CBS and Hema-Quebec
Figure 1. Kaplan-Meier survival curves of HIV-positive (n = 660) and HIV-negative
(n = 1767) individuals with hemophilia in Canada (1982-2003)
Arnold, D. M. et al. Blood 2006;108:460-464
Copyright ©2006 American Society of Hematology. Copyright restrictions may apply.
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1988 – 1992 (N= 4,588)
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Recipients randomized to:
 Surrogate testing NEG (‘withhold’ group)
 Routine screening (‘no withhold’ group)
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Outcome: post-transfusion hepatitis:
 ALT increased to at least 2.5 times ULN
 Other causes of abnormal liver function excluded
 HBV DNA
 HCV ELISA, PCR
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Transfusion Transmitted HIV and hepatitis
was a disaster that affected every country
worldwide
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8 month lag between implementation of HIV
screening In US and in Canada
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Lack of implementation of surrogate testing
for NANB hepatitis
1.
2.
3.
4.
5.
6.
7.
8.
Compensate the victims
Safe, Free, Sufficient, Accessible System
Single, public, open, independent operator
Promote appropriate use of blood products
Funded by hospitals
Creation of a national database
10% for Rx&D
Mandatory reporting of adverse events
1.
2.
Precautionary Measures
Governance
“…action to reduce risk should not await scientific
certainty. When there was reasonable evidence that
serious infectious diseases could be transmitted by
blood, the principal actors in the blood supply
system in Canada refrained from taking essential
preventive measures until causation had been
proved with scientific certainty. The result was a
national public health disaster.”
Krever H. Government of Canada 1997
To ensure public safety, precautionary
measures should be adopted despite
incomplete scientific information.
Wilson K, CMAJ 2007
“Responsibility for the blood system is fragmented…
the various functions integral to the supply of blood,
such as regulation, funding and planning, are
undertaken by different stakeholders… This lack of
definition may affect accountability within the
system, and ultimately its safety.”
Krever H. Government of Canada 1997
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Canadian Blood Services and Hema-Quebec
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CBS is insulated (arms-length, not-for-profit)
from provincial funders
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Highly structured, organized company
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Transfusion Medicine Residency Training
Program
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Funding for TM research
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Health Advocacy
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Unique approach to cost-effectiveness in
Transfusion Medicine
Custer TMR 2009
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Less attention paid to higher risks (e.g. noninfectious transfusion reactions)
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Address shaken public confidence
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Pathogen Inactivation
TRALI deferrals
Blood conservation
Custer TMR 2009
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Donor deferral
Donor self-exclusion
Transmissible disease testing
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HIV (antibody, NAT)
HCV (antibody, RNA)
Hepatitis B (surface antigen, DNA)
Hepatitis B core Antibody
Syphyllis
HTLV I/II
Chagas disease (implementation phase)
Diversion pouch
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HIV
Hepatitis C
Hepatitis B
HTLV
29
1: 2 – 3 million
1: 1 – 2 million
1: 150,000
1: 4.3 million
“It could therefore be argued that the PI of
blood products represents the quintessence
of the precautionary principle: almost all
potential for transfusion-transmissible disease
is eradicated often before the responsible
agent is even recognized…”
Alter, TMR 2008
Webert et al, Transfusion Medicine Reviews 2008
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For plasma products only
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Effective against all enveloped viruses
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Pooled platelets and plasma prepared with
plasma from male donors (2007)
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Female donors with prior pregnancy are
excluded from donating platelets (2009)
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Optimal use of Blood Products
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Autologous Transfusions
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Blood Substitutes
RBC transfusion trigger 70 g/dL (n= 418) vs. 100 g/dL (n= 420)
in critically ill patients (Hebert, NEJM 1999)
PLT transfusion trigger of 10 x109/L (n=135) vs 20 x109/L
(n=125) in patients with acute leukemia (Rubella, NEJM 1997)
Bone Marrow Transplantation, 2006
1091 units of plasma transfused for INR 1.1 – 1.85; follow up testing
available on 324 units (Dzik, Transfusion 2006)
70
FFP Orders (%)
60
50
P= 0.07
40
Inconsistent/ Inappropriate
Inconsistent/ Appropriate
P= 0.03
30
Consistent
P= 0.87
20
10
0
Phase I
Phase II Phase III
Arnold et al, ASH 2009
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CBS to manage donors for solid organ transplantation.
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Merge clinical and laboratory TM.
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Unified approach to donors (CBS) and recipients
(hospitals).
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Need for rigorous RCTs with meaningful clinical
endpoints.
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Determination of reasonable cost-effectiveness.
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Re-evaluation of Krever recommendations; optimal
utilization of blood products.
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Fundamental changes to TM in Canada since
Krever 1997
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Precautionary Principal
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Arms-length governance
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From “reactive” to “proactive”
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Blood conservation, optimal utilization
continues to be a key safety issue