Transmissible Spongiform
Encephalopathies
Advisory Committee Meeting
February 8, 2005
Silver Spring, MD
Topic
3: Deferral of Blood and Plasma
Donors for History of Transfusion in European Countries
In
January 2002, FDA recommended deferral of blood and plasma donors who received
blood transfusions in the U.K. since 1980 as an additional safeguard against
potential transmission of vCJD by blood products. FDA seeks the advice of the Committee whether this deferral now
should be expanded to include history of transfusion in other European
countries.
At the October 14, 2004 meeting of the TSE Advisory
Committee, FDA asked the Committee to consider whether any modifications of
protective measures for the US blood supply were indicated. These discussions
were prompted by the recent observation of two cases of vCJD in individuals who
received transfusions derived from asymptomatic blood donors who later
developed vCJD. One of these cases was heterozygous for met/val at codon 129
and neurologically asymptomatic at the time of death, but exhibited prion
protein in the lymphoid tissues. This scenario potentially reflects
longer-incubation vCJD infection in met/val heterozygous individuals who may
have been exposed to the vCJD agent. The committee did not recommend additional
donor deferral actions at the October, 2004 meeting. However, there was
discussion in two areas: a) the predictive value of the donor travel/residence
eligibility questions, and b) the possibility that deferral for transfusion in
other European countries outside of the UK may be worthy of additional
consideration.
French Health authorities recommended deferral of
donors that had previously been transfused in 1998. In December 2004 the Dutch Health Ministry announced that
individuals who had received any blood transfusion since 1980 would no longer
be eligible as blood donors. This policy resulted in an estimated 8% loss of
the Dutch donor base.
Few data are available to assess the potential for
secondary transmission of vCJD in the US from a donor with prior parenteral
exposure to vCJD by transfusion or other means. FDA current donor deferral
recommendations are based on a dietary risk (and approximate vCJD case ratio)
for France that is 5% of the UK risk
and, for the rest of Europe, is 1.5 % of the UK risk. These risks are based upon observed BSE incidence. At the October
2004 TSEAC meeting, FDA presented estimates that additional blood donor loss
from deferrals for transfusion in a broader geographic area of BSE endemicity
would be 1.4 per 10,000 for prior transfusion in France, and 3 per 10,000 for
prior transfusion elsewhere in non-UK Europe.
Deferral for any history of transfusion since 1980 among US donors would
result in the approximate loss of 5% of the US donated blood supply.
Corresponding loss estimates for Source Plasma donors are not available, but
(due to age-specific increases in prevalence) are likely to be lower based upon
the younger mean age of the donor base.
The negative predictive value of geographically
based donor eligibility criteria is also difficult to estimate due to the
inherent difficulties in validation. Donor survey research conducted in the
early to mid 1990’s indicated that false negative donor responses to medical
and behavioral questions as assessed by a subsequent anonymous survey tool, may
occur in 2-3% of donations.
Post-donation information related to geographic exposures continues to
comprise a high proportion of biological product deviation reports submitted to
FDA, indicating that improvements in current donor eligibility determinations
are still needed. A major effort to
improve and standardize the donor interview process has been underway by the
blood community in collaboration with FDA and other Agencies. This effort includes the cognitive
evaluation of all donor questions in an effort to maximize understanding by the
broadest segment of donors.
Relevant to any further consideration of a deferral
for donors transfused in Europe is the observation that for many years a large
proportion of the New York metropolitan area red blood cell supply was imported
from US-licensed collection facilities
in Germany, Switzerland and the Netherlands. The blood from these facilities
(Euroblood) was provided for more than thirty years beginning in the early
1970’s and constituted the only licensed blood components imported into the
US. The following are some key
observations about Euroblood:
·
The Euroblood program
began in the early 1970’s to address chronic RBC shortages in NY area (due the
presence of numerous tertiary care facilities)
·
During its peak
period, the Euroblood program represented one third of the New York area RBC
supply and approximately 2.0 % of the total US RBC supply
·
200 New York
Metropolitan-area hospitals were supplied with Euroblood over the 30 year
period of importation providing transfusions to an estimated >4 million
recipients
·
In the absence of a
massive lookback effort, Euroblood recipients currently living in the US are
largely untraceable.
·
The Euroblood program ended in the months prior
to 10/31/02, when the FDA recommendations resulted in deferral of whole blood
donors for > 5 years travel/residence in Europe.
While a policy to defer any individuals transfused
in Europe would result in marginal donor loss, such a policy would not address
the US recipients of Euroblood since 1980.
Recent
epidemiologic observations about vCJD in France and elsewhere, including
current estimates of the potential for transfusion-transmission will be
presented during the session to assist the Committee’s deliberations.
Questions
for the Committee
1. Based upon
the available scientific information, does the committee recommend deferral of
blood donors transfused since 1980
2. Based upon
the available scientific information, does the committee recommend deferral of
Source Plasma donors transfused since 1980