Blood Safety Summary - January 199
DATE: February 17, 1998
TO: Interested Parties
FROM: Stephen D. Nightingale, NM, Executive Secretary Advisory Committee on Blood Safety and Availability
SUBJECT: Summary of Third Meeting Advisory committee on Blood Safety and Availability
Hubert H. Humphrey Building, Room 800
200 Independence Ave., SW
Washington, DC 20201
January 29 and 30, 1998
Voting members present were Dr. Arthur Caplan, Chair; Mr. Larry Allen, Dr.
James AuBuchon, Dr. Michael Busch, Dr. Ronald Gilcher, Dr. Edward Gomperts,
Dr. Fernando Guerra, Dr. Paul Haas, Dr. William Hoots, Ms. Carolyn Jones,
Dr. Dana Kuhn, Ms. Tricia O'Connor, Dr. John Penner, Dr. Jane Piliavin, Dr.
Eugene Schiff, Dr. Marian Secundy, and Mr. John Walsh. Non-voting members
present were Dr. Mary Chamberland, Dr. Eric Goosby, Dr. David Feigal, Dr.
Paul McCurdy, and Dr. David Snyder. Dr. Kristine Moore, Consultant to the
Committee, was also present, as were Stephen Nightingale, MD, Executive Secretary,
and CDR Lawrence McMurtry, Deputy Executive Secretary.
The meeting opened with Dr. John Eisenberg, Acting Assistant Secretary for
Health, reading a letter from the Secretary to Dr. Caplan. The text of the
letter is as follows:
Dear Dr. Caplan:
Thank you for your thoughtful recommendations for persons inadvertently
exposed to
hepatitis C through blood transfusion. Your recommendations have greatly
assisted the Department's extensive review of this matter.
"I support your recommendation for the use
of direct notification efforts to reach those individuals who received a
transfusion from a donor who later tested positive for hepatitis by a confirmed
second generation screening test. I also support your recommendation for
a public and provider education effort directed at those who received blood
before this second generation screening test was available. This education
effort will also benefit others at risk for hepatitis C, regardless of the
source of their risk."
In addition, I intend to go beyond your recommendations. I consider these
steps to be only the first phase of a comprehensive plan to address this
significant public health problem. It is my intention to reach effectively
as many people at risk as we can. Todays decision will allow us to move
immediately to address concerns among transfusion recipients at greatest
risk. At the same time, we will educate the public at large, evaluate our
efforts, and take even more steps to address unmet needs as we identify
them.
I am directing the Public Health Service Blood Safety Committee, chaired
by the Blood Safety Director, to meet regularly to review progress in these
efforts and make appropriate recommendations for further action. We will
keep you informed of our progress.
Sincerely,
Donna E. Shalala
Dr. Robert Rohwer, Veterans Administration Hospital, Baltimore, MD, then
discussed animal models of Creutzfeldt-Jacob Disease (CJD) and the relevance
of these animal models to the human disease. He noted that prior experiments
at NIH have failed to demonstrate transmission of CJD from the blood of affected
humans to primates. He also noted that claims of transmission of CJD from
the blood affected humans to rodents are not widely accepted.
Dr. Rohwers experiments use brain tissue from sheep with scrapie, a transmissible
spongiform encephalopathy (TSE) which has clinical and pathological features
similar to human CJD Hamsters inoculated with this sheep brain tissue develop
a TSE referred to as hamster-adapted scrapie. When the hamster develops signs
of hamster-adapted scrapie, roughly two months after inoculation, it is sacrificed.
The first 2 cc of blood from the sacrificed hamster are transfused into a
healthy hamster, and the remainder of the blood (or blood fractions such as
buffy coat or plasma fractions such as Cohn Fraction V) is inoculated in 50
micro liter aliquots directly into the brain of other healthy hamster.
Dr. Rohwer has observed that intracerebral inoculation transmitted CJD in
22 of 22 hamsters. However, transfusion transmitted CJD in only 1 of these
22 hamsters. Furthermore, subsequent experiments have so far failed to demonstrate
transmission by transfusion. These experiments have also demonstrated intracerebral
transmission by whole plasma and Cohn plasma fractions I, I- U, and III, but
not by Cohn Fractions IV or V. Intracerebral transmission was also demonstrated
when human blood spiked with brain tissue from affected hamsters was used
instead of blood from an affected hamster.
Dr. Rohwer then discussed the probability that a human transfusion donor
would subsequently develop CJD, which is the incidence per mi4lion population
per year (1) times the incubation period of the disease (40 years): 40 per
million donors or I per 25,000 donors. Since the average pool size for plasma
fractions is about 30,000, it is virtually certain that recipients of that
pool will be exposed to blood from someone who will subsequently develop CJD.
Dr. Rohwer concluded by emphasizing the apparent differences between classic
human CJD, the animal model he was studying, and "new variant" (nv) CJD. Classic
CJD appears to have been present for hundreds of years; nvCJD only recently
jumped species from cows, where it produces bovine spongiform encephalopathy
(BSE) or Mad Cow disease, to humans. Dr. Rohwer did not feel that extrapolating
work done on classic CJD or his animal TSE models to nvCJD was warranted.
In the following discussion, Dr. Rohwer discussed the possibility of 'intraspecies
recycling,"a situation in which affected blood donors would die before they
developed symptoms of a disease, increasing the incidence of silent transmission.
If this has actually happened, however, the incidence of new cases should
be increasing. In the case of classical CJD this has not been observed; in
nvCJD it is not yet clear whether this is happening or not.
Dr. Lawrence Schonberger, Centers for Disease Control and Prevention, Atlanta,
GA, then reviewed the epidemiology of classic human CJD. He presented the
data in support of the CDC position that the risk of transmission of classic
CJD by blood transfusion is small and remains theoretical. No such transmissions
have been confirmed so far. Surveillance has been sufficient to identify transmission
of CJD by human growth hormone and by dura mater grafts and stereotactic EEG
equipment. Case-control studies do not identify blood transfusion as a risk
factor for CJD. The reported incidence of CJD has not increased from 1979
to 1995, and the preliminary 1996 figure of 218 CJD cases is within the previous
range. No hemophiliacs have as yet been found to have CJD. No one who has
received blood from a donor who subsequently developed CJD has so far developed
CJD.
Dr. Schonberger stated that there are legitimate concerns about the appropriateness
of current CJD withdrawal policies. The vast majority of product is used before
withdrawal is ordered, the cost is substantial, and shortages are created.
The discussion following this presentation focused on whether CJD was under
recognized, particularly in those with comorbid conditions such as hemophilia
and, specifically, ADDS.
Dr. Robert Will, National Creutzfeldt-Jacob Surveillance Unit, Edinburgh,
Scotland, UK, then discussed nvCJD. nvCJD differs from classic CJD in that
nvCJD has a younger age at onset, shorter incubation time, predominantly psychiatric
and sensory manifestations, a characteristic atypical electroencephalogram,
distinct neuropathology, and lymphoreticular extracranial involvement. The
epidemiologic link of nvCJD to BSE is being confirmed by animal experiments
in which material from both nvCJD and BSE causes the same distinct lesions.
These observations form the basis of the UK decision to withdraw blood products
if a donor subsequently develops nvCJD, but not if a donor subsequently develops
classic CJD.
Dr. Clarence Gibbs, National Institutes of Health, Bethesda, NM, then discussed
present directions of research on TSEs. Dr. Gibbs enumerated the human and
animal TSES; the latter include, in addition to BSE and scrapie, mink encephalopathy
and chronic wasting disease of deer and elk. The NIH supports studies of the
pathogenesis of TSES, including the work for which Dr. Stanley Prusiner recently
received the Nobel Prize. The NIH also supports work on development of diagnostic
tests for human and animal TSES.
After a lunch break, Dr. Lola Lopes (University of Iowa, Iowa City, IA) presented
data that individuals confronted with risky choices are influenced by the
shape of the distribution of the various possible outcomes and not just by
the mean of all possible outcomes. She then discussed her research on the
hypothesis that varying responses of different individuals to risky choice
can be explained by differences along an axis between security and potential,
and along a different axis called aspiration. Finally she discussed differences
in estimates of risk between experts and the public at large, and she pointed
out that these differences were less when the public had confidence in experts
in that particular area.
Dr. Mark Weinstein (Food and Drug Administration, Rockville, NM) then described
current FDA policies regarding TSES. He reviewed the December 11, 1996 FDA
memorandum which requires that all products for injection be retrieved and
destroyed if a donor is subsequently found to have CID or be at risk for CJD
unless that risk is a single family member with CJD, in which case plasma
derivatives using plasma from that donor can be used for injection. Recipient
notification is left to the discretion of others. He also reviewed the recommendations
of the FDA Transmissible Spongiform Encephalopathy Advisory Committee meeting
of October 6 and 7, 1997, which were exceptions to withdrawals should be considered
only for life- or health- sustaining products in short supply, that albumin
could be exempted from withdrawals only when used as an excipient for a non-vaccine
or non-plasma product, and that decisions about manufacturing process reagents
could be made on a case-by-case basis. Dr. Weinstein then gave examples of
how these policies were currently being translated into practice.
After a recess, the Advisory Committee heard presentations from David Cavenaugh,
Committee of Ten Thousand; Jan Hamilton, Hemophilia Federation; Jerry Winkelstein,
MD, h-nmune Deficiency Foundation; Donald Colbum, National Hemophilia Foundation;
Roslyn Romtovian, NM, American Society of Clinical Pathology; Richard Davey,
NM, American Red Cross; Barry Wenz, Pall Corporation; Margaret A. Somerville,
Consultant to Pall Corporation; Paul Just, Premier, Inc,; Jason Babilak, International
Plasma Producers Industry Association.
A brief discussion of the framework for subsequent discussion by the Committee
was followed by adjournment.
On January 30, 1998, Dr. Edward Gomperts described processes by which recombinant
products are produced in industrial quantities.
The Committee then held an extensive discussion. The following recommendations
were proposed and approved:
We recommend that the Public Health Service coordinate an effort to develop
a report within six months that will address issues of existing and emerging
transmissible spongiform encephalopathies. The report should make specific
reference to
Food borne transmission, particularly through consumption of central nervous
system tissues;
latrogenic transmission; and
Transmission through transfusion of blood components and plasma derivatives.
National and international surveillance of transmission in both humans and
animals, education of providers and the public, needed resources for research,
prevention strategies, and efforts in other countries also should be addressed
in this report.
2. We recommend that the Public Health Service, professional groups, and
patient advocates emphasize the importance of postmortem examination to the
protection of the public health, and that they support the training of physicians
to recognize new pathological patterns of emerging disease in autopsy tissues.
3. We recommend nationwide standardization of procedures for screening donors
at risk for transmissible spongiform encephalopathies.
4. We recommend that the National Institute of Health specify its needs for
research and infrastructure support necessary to promote research on the transmissible
spongiform encephalopathies, with particular reference to human and animal
tests which can discriminate among these conditions within each species.
5. We recommend that during the next year the Food and Drug Administration
work with industry and appropriate consumer groups to relax current Creutzfeldt-Jacob
disease guidelines on quarantine and withdrawal of blood products to the extent
necessary to relieve product shortages.
The Committee then turned to Old Business. There was a brief discussion of
the Secretarys letter to the Chairman of the Committee. The Committee requested
a report prior to its next meeting about the implementation of the Secretarys
initiative regarding hepatitis C and blood safety.
Then Committee then turned to New Business. The Committee made a several
recommendations for future agenda items, including the suggestion that it
should address the issue of shortages of blood products in more detail. The
meeting was then adjourned.
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