Page 2047 - Hematology_ Basic Principles and Practice ( PDFDrive )

1818 Part XI Transfusion Medicine

the reports of transfusion-associated cases, and some autochthonous There are no documented cases of transfusion transmission of
infections triggered efforts to mitigate the risk for transfusion- sporadic CJD, the familial or iatrogenic forms, and cohort studies of
transmitted Chagas disease in the United States. Questioning intensively transfused patient groups have failed to establish any
donors about region of birth or extended stay and transfusion in epidemiologic association in both the United Kingdom and the
Chagas-endemic areas could interdict 75% of infected donors but United States. 22,76 In an ongoing look-back effort, no cases of CJD
would result in deferral of large numbers of noninfected donors. have been observed among 461 recipients (of whom 85 were still alive
Leukoreduction decreases T. cruzi transmission in a mouse model as of December 31, 2008) of blood components from 40 donors
by 50% to 70%, consistent with Leishmania and the rickettsia subsequently diagnosed with CJD. A case-control study of CJD
Anaplasma. Pathogen-reduction techniques successfully decrease T. patients, compared with control patients with CJD ruled out, found
cruzi viability in plasma and cellular products. a fivefold increased risk for CJD with a history of transfusion more
Serologic screening, used for many years in Latin America, was than 10 years before TSE onset, but the authors recognized critical
chosen as the preferred strategy for the United States. The first sources of bias in their methods and their findings are unconfirmed.
serologic test for screening blood donors, based on a T. cruzi whole- Nevertheless, as a result of the iatrogenic transmissions and long
parasite lysate, achieved FDA licensure in December 2006, and incubation period of the disease (as demonstrated in growth hormone
voluntary screening commenced in early 2007. Approximately 1 per transmissions), concern arose in the mid-1990s that CJD transmis-
30,000 donations showed confirmed reactive serologic results, a lower sion could occur from asymptomatic donors to transfusion or deriva-
prevalence than estimated. In 2010 the FDA licensed a second assay tive recipients. This theoretical risk resulted in lifetime donor deferral
that uses chimeric recombinant antigens and in 2011, a licensed requirements for iatrogenic exposure to or a family history of classic
supplemental test using the same antigen constructs was FDA CJD.
licensed. Seropositive donors are overwhelmingly immigrants from Like classic CJD, vCJD is a fatal, degenerative neurologic disease.
T. cruzi–endemic countries with asymptomatic chronic infections, It occurs in younger patients than classic CJD and has distinctive
although a small number of seropositive donors may have acquired clinical, radiographic, histopathologic, and biochemical features. The
the infection in the United States via vertical transmission from first reports of vCJD from the United Kingdom were published in
infected immigrant mothers, or very rarely by autochthonous vecto- 1996. The etiologic agent is the same prion that causes BSE or “mad
rial transmission. From the investigation of antibody-positive donors cow disease.” Transmission of the BSE prion to humans occurred by
lacking any immigration or maternal risk factors, autochthonous consumption of beef and other bovine products containing infectious
transmission has been estimated to occur at the rate of 1 per 354,000 neural or reticuloendothelial tissue. In the United Kingdom the
donors. 73 vCJD epidemic followed a massive epidemic of BSE in the 1980s
Look-back studies involving recipients of prior donations from and 1990s. The latter was traced to the recycling of material from
those found positive for T. cruzi antibodies on a subsequent donation dead sheep and cattle (offal) into feed for cattle. This practice was
showed rates of transfusion transmission much lower than predicted. banned in 1988, and the vCJD outbreak subsided after a peak of 28
Only two occurred (0.8%), both from the same apheresis platelet cases in 2000. The number of new vCJD diagnoses in the United
donor born in Argentina, among 253 recipients tested. In light of Kingdom rose steadily in the first few years after 1995 from 3 in 1995
these findings, testing donors is now required only once rather that to 28 in 2000, but decreased since then to 5, 5, 5, 1, 3, 3, and 2
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at each donation. Concern that those tested once might contract from 2005 to July 2011, by which time 175 (172 deaths, 3 living)
T. cruzi during travel or within the United States seems unfounded definite or probable cases of vCJD had been reported in the United
in that no seroconversions have been observed in more than 4 Kingdom. An additional 49 cases have been diagnosed elsewhere,
million blood donors during 6 million person-years of follow up. mostly in France and several other European countries. A few cases
The unexpectedly low rate of transmission may relate to differences have been identified outside Europe, including 3 cases in the United
in blood component processing and storage in the United States States (2 associated with exposure in the United Kingdom and 1 in
compared with Latin America (absence of the transfusion of fresh Saudi Arabia), 2 from Canada, and 1 each from Japan, Taiwan, and
whole blood), some underrepresentation of platelet donors in the Saudi Arabia. Most but not all of the patients with non-European
look backs completed to date, or other biases. Although all donors cases had more than 6 months’ exposure in the United Kingdom
are asked a question about having a history of Chagas disease, with during the BSE epidemic. Although it appears that the vCJD out-
the advent of sensitive testing, the question has no residual value and break is waning (and is much smaller than initially feared), concern
has been removed from the donor history questionnaire according to persists that there could be a second wave of the epidemic caused by
FDA rules. 75 delayed onset of the disease in infected individuals. This is based in
part on observations of abnormal prion protein accumulation in
random surgical tissue samples in the United Kingdom, which may
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES represent preclinical vCJD disease. In one retrospective study, 3 of
12,674 appendectomy and tonsillectomy specimens from persons 20
The transmissible TSEs (prion diseases) are rare, lethal neurode- to 29 years of age were positive. Furthermore, a critical polymorphism
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generative diseases generally accepted to be caused by nucleic at codon 129 of the PrP gene coding for methionine or valine leads
acid–free proteins called PrP TSE , as distinguished from the normal to variation in the susceptibility to and incubation period of human
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cellular protein, PrP . The existence of additional factors has not TSEs. All of the clinical cases reported to date are methionine homo-
been excluded, but current consensus supports the involvement of zygotes. Because only 37% of the general British population is
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infectious proteins. PrP TSE is an abnormal conformation of PrP that homozygous for methionine, and are maximally susceptible to vCJD,
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induces transformation (recruitment) of additional PrP to PrP TSE , a larger population (52%) of heterozygotes and valine homozygotes
resulting in deposits of insoluble aggregates in central nervous system (11%) may be at risk for asymptomatic infection in a prolonged
tissue followed by progressive dementia and other characteristic neu- incubation period.
rologic findings. Classic Creutzfeldt-Jakob disease (CJD) is diagnosed Four transfusion-transmitted infections with the vCJD prion have
at a rate of approximately one case per million population per year been reported in the United Kingdom. Although they may have
worldwide. It occurs as sporadic CJD, vertically transmitted familial developed vCJD independent of transfusion, this possibility is
diseases caused by germline mutations in the human PRNP gene regarded highly unlikely based on epidemiologic and statistic consid-
(e.g., fatal familial insomnia and Gerstmann-Straüssler-Scheinker erations. Three of the four cases were diagnosed with clinical vCJD
syndrome), iatrogenically transmitted infection (e.g., from dura 6.5, 7.8, and 9 years after receiving nonleukocyte reduced RBCs or
mater implantation, contaminated surgical equipment, injection of a blood component from two different donors who developed clinical
human pituitary-derived growth hormone, or corneal transplant) symptoms of vCJD 40 and 21 months after donating. These three
and can be spread horizontally (Kuru associated with consumption with symptomatic disease were homozygous for methionine at codon
of human brain during ritual cannibalism is of historical interest). 129. The fourth case was heterozygous (methionine/valine) and had