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

29

“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