Page 2042 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 120 Transfusion-Transmitted Diseases 1813

among infected subjects), along with deferrals for residence in affected proliferation occurs more rapidly in platelet concentrates stored at
areas. Chikungunya symptoms are similar to those of dengue, but room temperature than in red cells maintained at 4°C (39.2°F).
without the impact upon the circulatory system. Arthralgia is, The rate of bacterial contamination in allogeneic platelets was
however, a prominent symptom and may be prolonged. Routine estimated at 1 per 1000 to 3000 units with life-threatening septic
testing is not currently available. reactions occurring in one per 15,000 to 100,000 recipients before
routine implementation of culture-based tests to detect bacteria in
apheresis platelets in 2004. These tests reduced contamination rates
ZIKA VIRUS to approximately 1 per 5000 to 8500 platelet units. Clinical septic
reactions occur in approximately 30% of recipients receiving con-
Zika virus is another tropical arbovirus of the flavivirus group. Again, taminated platelets. Bacterial contamination was responsible for 33
first recognized in Africa, it has been circulating in the Pacific islands of 267 (12%) of transfusion-related deaths reported to the FDA from
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at relatively modest levels. In 2007 the first human outbreak was 2005 to 2009. In subsequent reporting periods (2008–2012 and
recognized on the island of Yap in Micronesia with subsequent 2010–2014) bacterial contamination of platelets (primarily Staphylo-
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spread in 2013 to French Polynesia. Testing performed in Polynesia coccus aureus and Serratia marcescens) were responsible for 13 of 198
showed 2.8% of presenting donors to have Zika virus RNA. Within (7%) and 11 of 176 (6%) recipient fatalities (www.fda.gov/
2015 Zika virus and associated disease emerged in Brazil and has BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/
now spread to beyond other South and Central American countries, TransfusionDonationFatalities/). The downward trend is undoubt-
Mexico, and the Caribbean including travel-associated cases in the edly caused by interventions that have been put into place (increased
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United States. A particular concern is that the infection seems to attention to arm scrub, improved antiseptic solutions used, sample
be associated with an unexpectedly high and troubling incidence of diversion of the first 40 mL or so containing the skin plug and bacte-
microcephaly, a neurologic developmental abnormality. 55,56 Increases rial testing). Only acute hemolytic reactions and TRALI are respon-
have been noted, particularly in Brazil, where it is believed that the sible for more fatalities in the referenced reporting periods. However,
increase is a consequence of maternal infection and transmission to there is consensus that these reactions are badly underrecognized and
the developing fetus. In addition, during the outbreak in Polynesia, underreported. Culturing fails to detect 50% to 75% of contaminated
a 20-fold increase in the number of reported Guillain-Barré syn- units. This undetected contamination occurs largely because minimal
drome cases were reported; a similar increase is also being noted in bacterial levels, present when cultures are obtained, yield culture
Brazil. Other than mosquito transmission, like dengue, transfusion aliquots without bacteria. Subsequently the few bacteria remaining
transmission has been reported. Unlike the other mosquito-borne in the blood bag can grow out during storage, producing transfusions
viruses, Zika appears to be sexually transmitted (and can be recovered with significant bacterial levels. To minimize this, collection facilities
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from urine and semen). The World Health Organization has called generally hold apheresis platelets for approximately 24 hours after
a public health emergency of international concern to increase sur- collection before sampling for culture to allow low bacterial inocula
veillance and vector control and to expedite the development of to proliferate, improving the sensitivity of culture. As mentioned,
diagnostics, treatment, and vaccine development. Given the similar- improved skin antisepsis and diversion for laboratory testing of the
ity to and relationship with dengue, there are concerns about the first 40 mL of blood, which contains the skin plug, provide further
spread of Zika virus and local transmission in the continental United reduction of contamination rates, transfusion reactions, and fatality
States. Most recently (August 2016), the implementation of univer- rates by lowering the bacterial load that otherwise would enter the
sal, individual donation NAT for Zika virus RNA has been required final component container.
for all blood collected in the United States. Septic transfusion reactions should be suspected when one or
more of the following occur within 1 to 4 hours of transfusion:
temperature elevations greater than 1–2°C (1.8–3.6°F), chills and
PANDEMIC INFLUENZA A rigors, tachycardia more than 120 beats per minute or an increase of
40 beats per minute, or an increase or fall in systolic blood pressure
There was interest in the transfusion safety implications of influenza of greater than 30 mmHg. Additional signs and symptoms can
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A even before the swine origin A-H1N1 pandemic of 2009–2010. include nausea, vomiting, diarrhea, bleeding, oliguria, or septic
Viremia in donors, and the potential for infection of recipients were shock. Septic transfusion reactions may be confused with hemolytic
discussed during meetings of an AABB pandemic influenza planning transfusion reactions, febrile, nonhemolytic transfusion reactions, or
task force as early as 2008, based on old literature demonstrating the TRALI.
virus in the blood of experimentally infected volunteers and case Platelet concentrates contaminated with Staphylococcus aureus,
reports of viral dissemination during human infection with highly Serratia marcescens, Staphylococcus epidermidis, Escherichia coli, and
pathogenic avian A-H5N1 virus. Subsequent studies have failed to Streptococcus species account for most of clinically recognizable reac-
identify influenza viruses in donors drawn in US communities during tions. Propionibacterium acnes is a frequent culture isolate from
periods of high seasonal influenza activity or in donors with the onset platelets during storage when an anaerobic culture is also performed
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of influenza-like illness immediately following donations. The but is not believed to be responsible for a significant number of
current consensus is that pandemic influenza is not likely a threat to reactions. A clinically relevant case of Clostridium perfringens, another
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blood recipients, but that disruption of the blood supply in a severe anaerobe, has been reported. The bacterial dose in platelet concen-
pandemic is a more important possibility, requiring careful advance trates and species virulence correlate with the clinical outcome. Bacte-
5
planning. rial concentrations greater than 10 colony-forming units (CFU)/mL
are more likely to result in severe reactions or fatalities. Alternatively,
4
low concentrations, 10 or fewer CFU/mL of skin organisms, fre-
BACTERIAL CONTAMINATION quently elicit no reaction. Endotoxin elaboration by gram-negative
organisms is associated with the most severe reactions, but the vast
Bacterial contamination of red cell and platelet components occurs majority of gram-negative organisms are easily detected by bacterial
primarily as a result of the inability to achieve complete skin disinfec- culture.
tion at the donor phlebotomy site, where bacterial populations In addition, bacteria grow at variable rates. S. epidermidis grows
survive in skin appendages below the accessible surface and contami- slowly, and P. acnes requires on average 3 days for detection. Because
nate skin plugs made by the phlebotomy needle and enter the blood collection agencies continue bacterial culturing until the platelet unit
bag. Transient asymptomatic bacteremia at the time of blood dona- expiration date or detection of growth, there is further opportunity
tion, a break in technique during pooling the contents of or sealing to intercept released platelets that have not been transfused and to
blood containers, disruption of blood bag integrity or its contamina- alert physicians about the potential risk for bacterial contamination
tion during manufacturing are other rare sources. Bacterial in cases where the units have been administered. However, the vast