Page 2036 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 120 Transfusion-Transmitted Diseases 1807

revised guidelines for laboratory diagnosis of HIV infection (http:// medicine community in the early 1980s to the emergence of human
dx.doi.org/10.15620/cdc.23447). 20 immunodeficiency virus (HIV) in the blood supply and the recogni-
Recent studies have shown that the predominant risk factors for tion of the scope and severity of post-transfusion non-A, non-B
HIV infection among 149 male infected blood donors surveyed hepatitis (subsequently hepatitis C [HCV]) following that. It reflects
retrospectively continues to be a history of MSM behavior (62% also the “dread fear” associated with transfusion-associated HIV. This
in cases vs. 2% in controls) or of a male having sex with an reaction is seen when devastating, unpredictable, and stigmatizing
HIV-positive individual (26% in cases and none in controls). Of events threaten potential victims who have little ability to escape the
note, 50% of MSM activity occurred within the last 12 months. risk. This fear was validated by numerous transfusion-related HIV
Although in the past, injection drug use was also a prominent risk cases. It was amplified by widely publicized lawsuits, indictments, and
factor, this has decreased in prominence (24% in cases vs. 5% in criminal convictions of health ministers and policy makers in the
controls). 2 1980s and 1990s (l’affaire du sang contaminé in France addressing
In 2015 the US FDA formally reconsidered the original policy of HIV and Canada’s Royal Commission of Inquiry on the Blood
permanent lifetime deferral of MSM even once since 1977 and have System into blood collection agencies’ response to non-A, non-B
now issued Guidance permitting donation by those who have not hepatitis risk) (Fig. 120.1). (See box on Blood Safety Decision
engaged in MSM in the prior year, thus reducing the deferral period Making.)
to 1 year, in common with a number of other countries, including
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Australia and the United Kingdom (www.fda.gov/BiologicsBlood
Vaccines/GuidanceComplianceRegulatoryInformation/Guidances/ Human T-Lymphotropic Virus-1 and Virus-2
default.htm, Revised Recommendations for Reducing the Risk of
Human Immunodeficiency Virus Transmission by Blood and Blood Human T-lymphotropic virus-1 (HTLV-1) and HTLV-2 are closely
Products, Dec 2015). related deltaretroviruses with 60% to 70% sequence homology and
Most consider the blood supply in the developed world to be at shared tropism for T-lymphocytes. In contrast to HIV, HTLV is rarely
its highest historical safety level. This reflects incremental improve- present in cell-free plasma and shows little active replication in
ments in donor selection and history screening, blood testing, and infected humans. HTLV-1 is distributed worldwide, with endemic
process control that span four decades. For years, blood collection foci in southern Japan, the Caribbean, certain parts of South America,
professionals and government regulators formulated blood safety Africa, the Middle East, and Melanesia. HTLV-2 is endemic among
policy decisions in an apparent aim to achieve zero-risk blood supply. Amerindians in both North and South America and African Pygmies.
In part, this reflects the perceived delayed response of the transfusion An epidemic of HTLV-2 infections has occurred over the past 40 to

Blood Safety Decision Making
Not surprisingly, from the 1980s until now, donor deferrals and blood- smaller program in the United States, have emerged, supplying evidence
testing interventions have been rapidly, successively, and additively about a much broader range of transfusion hazards than just infections.
implemented for emerging and theoretical risks. Collection facilities For example, a data-driven decision to minimize plasma transfusions
introduced antibody testing to the HBcAg of HBV (anti-HBc) and ALT from potentially alloimmunized female donors resulted in a dramatic
testing as surrogates for non-A, non-B hepatitis, HIV-1 p24 antigen reduction in transfusion-related acute lung injury (TRALI) in the United
testing, then NAT for hepatitis C and HIV and subsequently HBV, Kingdom, and studies in the United States have reproduced this finding.
extensive deferrals for the risks attending transmissible spongiform These systems provide an opportunity for monitoring the risks
encephalopathies (TSEs,) NAT for West Nile virus (WNV), and antibody and benefits of new initiatives, (e.g., proactive pathogen reduction).
testing for Trypanosoma cruzi. The cost-benefit estimates for some of Pathogen-reduction processes (see box on Pathogen Reduction) offer the
these interventions exceeded by orders of magnitude generally accepted opportunity to abrogate most of the residual risk for all of the historically
thresholds but did not deter their adoption. In general, the implementa- important transfusion-transmitted viral infections, bacterial contamination
tion of these measures was undertaken by the blood providers, but of platelets, babesiosis and malaria contaminated red cells, WNV infec-
at the time of writing, it is unlikely that this reactive approach can be tions, and Chagas disease. Pathogen reduction could eliminate the often
sustained in the current health care–reform environment and in the face lengthy, reactive, iterative paradigm of emergence of a new pathogen in
of declining funding for blood providers, at least in the United States. the population, recognition of a material threat to transfusion recipients,
Application, after HIV entered the blood supply, of a stringent form development of donor-deferral strategies followed by development and
of the precautionary principle (originally promulgated for environmental refinement of test systems that has characterized our historical approach.
protection, not transfusion safety) pushed decision making toward avoid- Critically, broadly active pathogen-reduction processes offer a layer of
ance of all risks. The precautionary principle promotes implementation protection against unsuspected emergence of new agents. If already
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of measures to mitigate risk even if evidence of a risk is incomplete. It in use, they would need only to be validated as active against a new
is supposed to be tempered by proportionality; that is, any measures agent or appropriate model agents. The challenge with this approach is
adopted are to be proportional to the risk and with those used in similar broad-based availability (all components) and wide-scale acceptance,
circumstances, but some have argued that this has not been the case the impact on product quality, and the potential long-term toxicities that
with blood safety measures, at least by the metric of cost-benefit. Nev- may not be apparent in premarketing clinical trials or implementation
ertheless, although in potential conflict with evidence-based decision to date. 24–26
making, this approach resonated with policy advocates charged with More recently, as cost pressures for health care increase, transfu-
transfusion safety. In contrast, when the risk for transfusion transmission sion professionals are questioning whether the zero-risk paradigm
of variant Creutzfeldt Jakob (vCJD) disease (the human form of bovine remains relevant. A consensus conference held in Toronto in October
spongiform encephalopathy, BSE) emerged as theoretical, modeling was 2010 addressed concerns about “safety at any cost” and inconsistent
used to balance the perceived risk against the impact of extensive donor decision-making practices affecting the blood supply. This initiative has
deferrals on the adequacy of the blood supply and to arrive at a policy led to a definitive effort to establish a framework for risk-based decision-
decision. Some argue that the magnitude of risk does not justify the making under the direction of the Alliance of Blood Operators (www.
stringency of the donor deferral policy, given the small risk in a country allianceofbloodoperators.org/abo-resources/risk-based-decision-making/
that was not BSE endemic or lacked any BSE-contaminated materials rbdm-framework.aspx). The process involves risk identification, risk
in their food supply, but the process was the first to attempt to balance assessment, risk management, and risk communication, along with
risk with adequacy. Subsequently, vCJD was shown to be transfusion an assessment of risk tolerance, in the context of full and open com-
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transmissible. 22 munication with stakeholders. Risk will never be zero, and there is
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Hemovigilance programs, such as the Serious Hazards of Transfusion now a realization that cost considerations, politics, ideology, and public
(SHOT) in the United Kingdom and others in Canada, France, and a opinion cannot be ignored.