Page 2043 - Hematology_ Basic Principles and Practice ( PDFDrive )

1814 Part XI Transfusion Medicine

majority of septic reactions are associated with false-negative culture the discovery of the Australia antigen almost two decades later. More
tests because of sampling insufficiency as noted earlier. The overall than 100 transfusion syphilis cases were published before World War
rate of bacterial contaminated apheresis platelets is 1 per 5000 and II, and many more certainly occurred. The last alleged case of
for septic transfusion reactions is 1 per 107,000 distributed transfusion-transmitted syphilis in the United States, however, was in
components. 61 1966. Since then, hundreds of millions of components have been
Before the mid-1980s, platelet concentrates were stored for 7 days. transfused in this country without another recognized case. There are
Following reports of septic reactions, the shelf life was reduced to 5 multiple explanations for the disappearance of transfusion-transmitted
days to decrease the interval during which bacteria could proliferate. syphilis in addition to improvements in testing: (1) the dramatic
In the United States, blood suppliers distributed platelets from 2005 decline in the incidence of early syphilis in the United States over the
to 2008 with a 7-day shelf life following enrollment in an FDA- decades, more than an order of magnitude, reducing the reservoir of
mandated postmarket surveillance study (Post Approval Surveillance donors able to transmit; (2) the end of direct donor-to-recipient
Study of Platelet Outcomes, Release Tested [PASSPORT]) that transfusion combined with the loss of viability of Treponema pallidum
included testing for bacterial contamination by a sensitive culture in stored blood—the latter attributed to poor survival in refrigerated
method. Initial experience suggested that extended platelet storage RBCs and to the high oxygen tension in platelets stored at higher
coupled with bacterial testing substantially decreased platelet loss temperatures; (3) the ubiquitous administration of antibiotics for
from outdating. However, the PASSPORT study found 1 per 4329 trivial to serious viral, bacterial, and noninfectious clinical syndromes,
tested platelet products with negative bacterial cultures had bacterial especially to those sick enough to be transfused; (4) donor deferral
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growth when tested at the end of storage, 7 days later. Septic for behavioral correlates of syphilis risk (e.g., male sex with males,
transfusion reactions occurred in approximately 1 per 25,000 platelet occurrence of recent sexually transmitted infection in donors,
transfusions; some following infusion of 3-day stored platelets, most exchange of drugs or money for sex, injection drug use); (5) passive
with those stored 4 days or longer, leading to reinstatement of the surveillance for transfusion-transmitted syphilis compounded by the
5-day platelet shelf life. failure of recognition by physicians (who may have never seen syphi-
Alternative methods for detecting bacterial contamination include lis, venereal or otherwise); and (6) donor illness during spirochetemia
point-of-release testing in the hospital transfusion service. Considered severe enough to prevent their presentation to donate blood or
a supplement to culture-based testing, this assay can be used shortly causing deferral. The relative contributions of each of these factors
before issuing platelets for transfusion to detect units missed by early are unquantified.
culture. This rapid qualitative immunoassay tests for the presence of Most blood collection facilities screen donors with an automated
conserved bacterial antigens (gram-negative lipopolysaccharide and test for detecting treponemal antibodies (e.g., T. pallidum hemag-
gram-positive lipoteichoic acid). In one report using this test, 1 per glutination assay and T. pallidum particle agglutination assay;
3000 platelet doses contained gram-positive organisms when issued treponemal antibody confirmatory test usually follows using a
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3 or more days after collection. Other methods, under development variety of methods such as enzyme-linked immunosorbent assay
for mitigating septic platelet events, include microcolorimetry, bacte- (ELISA) or fluorescent treponemal antibody, absorbed (FTA-abs)
rial spore biosensors, real-time PCR, flow cytometry, and detection test; most blood centers further test donors with treponemal anti-
of other bacterial cell wall constituents. Pathogen-reduction technol- body reactivity using a nontreponemal test (e.g., rapid plasma reagin
ogy using licensed psoralens (Intercept) or riboflavin plus UV light [RPR]) to stage the reactivity as recent or past. Approximately 50%
provides an opportunity for inactivating multiple pathogens before of donors with confirmed positive treponemal test results have evi-
they can proliferate. Again, however, not all technologies inactivate dence of a treated syphilis infection. Donations with reactive syphi-
different bacterial isolates with the same efficiency. lis tests are generally discarded. Blood centers defer donors with
RBC bacterial contamination rates approximate 1 per 30,000 positive treponemal confirmatory tests; donors may be reentered
units with adverse clinical outcomes occurring in 1 per 500,000 (regardless of their nontreponemal test results) 12 months after
transfusions and fatalities occurring at a rate of 1 per 10 million. Most completion of treatment for syphilis. Treponemal and nontrepone-
septic reactions occur in units stored for 4 weeks or longer, reflecting mal false positivity occurs in healthy donors caused by cross-
the delayed growth of bacteria at 4°C (39.2°F). reactivity with a wide variety of infectious diseases other than
Bacteria isolated from contaminated red cell units include S. syphilis, in those with high-titer human leukocyte antigen (HLA)
marcescens, E. coli, Pseudomonas species (especially Pseudomonas fluo- antibodies, after some immunizations, with autoimmune disease
rescens), and Yersinia enterocolitica. The latter two are psychrophilic and other chronic inflammatory disease, and have increasing preva-
and known to proliferate in the cold. Gram-positive skin saprophytes lence with increasing age.
account for most of the organism-contaminating platelet concen- Most true treponemal antibody positives are the “serologic scar”
trates, with the remaining attributed to gram-negative organisms of remote (often treated) infection and pose no risk to blood recipi-
associated with occult bacteremia. ents. A recommendation to discontinue donor screening for syphilis
Immediate recognition of a platelet or red cell septic reaction and was made in 1985 but not acted upon initially because of the percep-
immediate discontinuation of the transfusion, supportive care, and tion that testing might be functioning as a surrogate for HIV or other
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antibiotic administration are the mainstays of therapy. Prevention transfusion-transmissible viruses. This hypothesis has been rejected,
relies on careful donor selection and scrupulous adherence to aseptic but, because the role of syphilis testing in the elimination of transfu-
techniques and precautions from component collection, processing, sion syphilis is unclear, syphilis testing continues even though it has
transport, and storage to transfusion at the bedside. The Gram stain no apparent value. Although small PCR studies of reactive donors
reveals bacteria in platelet concentrates contaminated with more than have been universally negative, rabbit inoculation studies using
5
6
10 to 10 CFU/mL. samples from confirmed reactive donors will likely be required to
A proportion of donors of platelet units contaminated with eliminate syphilis testing, and it seems unlikely the resources will be
Streptococcus bovis or Streptococcus infantarius have been found to have found to do a study of the required size.
colonic polyps or colon cancer.
Lyme Disease
SPIROCHETE INFECTIONS
Borrelia burgdorferi is the spirochete that causes Lyme disease, the
Syphilis most frequent tick-borne infection in North America and Europe.
The agent was discovered in 1977 during investigations of an arthritis
US blood banks first screened donors with a serologic test for syphilis cluster in Connecticut children. Cases reported in the United States
in 1938, and screening has been a regulatory requirement since 1958. doubled between 1992 and 2006 to almost 20,000. Geographic
It was the first test mandated for US donors and stood alone before distribution of cases is highly focused, with the majority of reported