Donald M. Arnold, MDCM MScProgram Director, Transfusion MedicineMcMaster UniversityCanadian Blood Services
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
Disclosures
The Past: “Tainted blood scandal”
The Present: What we learned
The Future: Where is TM headed
Blood is a life-saving commodity
Transfusion Medicine crosses all disciplines
There will always be new threats to the blood supply
People will continue to be harmed by blood
Highly emotional, political business
Justice Horace Krever, 1997
“The most influential report on public health in Canadian history”
-K. Wilson CMAJ 2007
1,000 infected with HIV30,000 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 NANBhepatitis
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
Copyright ©2006 American Society of Hematology. Copyright restrictions may apply.
Arnold, D. M. et al. Blood 2006;108:460-464
Figure 1. Kaplan-Meier survival curves of HIV-positive (n = 660) and HIV-negative (n = 1767) individuals with hemophilia in Canada (1982-2003)
1988 – 1992 (N= 4,588)
Recipients randomized to: Surrogate testing NEG (‘withhold’ group) Routine screening (‘no withhold’ group)
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
Transfusion Transmitted HIV and hepatitis was a disaster that affected every country worldwide
8 month lag between implementation of HIV screening In US and in Canada
Lack of implementation of surrogate testing for NANB hepatitis
1. Compensate the victims2. Safe, Free, Sufficient, Accessible System3. Single, public, open, independent
operator4. Promote appropriate use of blood
products5. Funded by hospitals6. Creation of a national database7. 10% for Rx&D8. Mandatory reporting of adverse events
1. Precautionary Measures2. 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
Canadian Blood Services and Hema-Quebec
CBS is insulated (arms-length, not-for-profit) from provincial funders
Highly structured, organized company
Transfusion Medicine Residency Training Program
Funding for TM research
Health Advocacy
Unique approach to cost-effectiveness in Transfusion Medicine
Custer TMR 2009
Less attention paid to higher risks (e.g. non-infectious transfusion reactions)
Address shaken public confidence
Pathogen InactivationTRALI deferralsBlood conservation
Custer TMR 2009
Donor deferral Donor self-exclusion Transmissible disease testing
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
HIV 1: 2 – 3 millionHepatitis C 1: 1 – 2 millionHepatitis B 1: 150,000HTLV 1: 4.3 million
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“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
For plasma products only
Effective against all enveloped viruses
Pooled platelets and plasma prepared with plasma from male donors (2007)
Female donors with prior pregnancy are excluded from donating platelets (2009)
Optimal use of Blood Products
Autologous Transfusions
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)
0
10
20
30
40
50
60
70
Phase I Phase II Phase III
FF
P O
rder
s (%
)
Inconsistent/ Inappropriate
Inconsistent/ Appropriate
Consistent
P= 0.07
P= 0.03
P= 0.87
Arnold et al, ASH 2009
CBS to manage donors for solid organ transplantation.
Merge clinical and laboratory TM.
Unified approach to donors (CBS) and recipients (hospitals).
Need for rigorous RCTs with meaningful clinical endpoints.
Determination of reasonable cost-effectiveness.
Re-evaluation of Krever recommendations; optimal utilization of blood products.
Fundamental changes to TM in Canada since Krever 1997
Precautionary Principal
Arms-length governance
From “reactive” to “proactive”
Blood conservation, optimal utilization continues to be a key safety issue