Page 2032 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 120

TRANSFUSION-TRANSMITTED DISEASES

Susan L. Stramer and Roger Y. Dodd

Adverse reactions following blood transfusion reflect immunologic, population, and an additional 12,400 were chronic hepatitis (www
pathophysiologic, and microbiologic events. This chapter presents .cdc.gov/hepatitis/statistics, Viral Hepatitis–Statistics and Surveil-
information about transfusion-associated viral, bacterial, parasitic, lance). It is estimated in the United States that approximately 12
and prion infections and discusses a number of emerging agents. million persons are infected, with 5000 deaths each year resulting
Transfusion-transmitted infection risk mitigation through blood from hepatitis B and its complications.
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donor screening and blood testing strategies are presented. The Based largely on data from parenteral exposures of health care
boxed discussions provide insights into interventions aimed at reduc- workers, HBV is 100 times more infectious than human immuno-
ing risk from known and emerging threats and new technologies for deficiency virus (HIV) and 10 times more infectious than HCV. The
reducing or eliminating microbial contamination. Red cell, platelet, predominant mode of transmission to adults and adolescents is
and plasma transfusion represent important therapeutic modalities through sexual contact. Forty percent have infected partners, 15%
for appropriately selected patients. Awareness of the hazards of are males having sex with other males, injecting drug users account
transfusion and the rate at which these events occur should enable for 14% of cases, and one-third have no identifiable risk. A recent
physicians to better determine the benefit/risk ratios when prescrib- study of risk factors in blood donors found to be infected with HBV
ing transfusions. found that of 292 infected donors surveyed, the characteristics most
frequently associated with infection were living abroad or having
immigrated to the United States (51% vs. controls at 6%), a family
HEPATITIS VIRUSES member infected with hepatitis (15% vs. 2%), having been in a jail
or detention for 3 nights or more (19% vs. 5%) and having taken
The hepatitis viruses can be classified according to their predominant illegal drugs (20% vs. 12%). 2
modes of transmission, parenteral and enteric, with the parenterally HBsAg is detectable in blood approximately 4 weeks (30 to 60
transmitted agents, hepatitis B virus (HBV) and hepatitis C virus days) after infection. Subsequently, immunoglobulin M (IgM) anti-
(HCV) dominating concerns about transfusion transmission because HBc antibodies appear coincident with symptom onset. High viral
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many individuals unknowingly infected with these agents become titers (10 genomes/mL) present at that time decline subsequently.
asymptomatic chronic carriers and may make blood donations. HBsAg persists transiently in acute infections for up to 4 months
(average 63 days). More recent data using extremely sensitive HBsAg
Parenterally-Transmitted Hepatitides assays for blood donation screening show the mean period of HBsAg
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duration to be 43 days. Antibodies against HBsAg (anti-HBs)
develop subsequently and are generally thought to protect against
Hepatitis B reinfection although recent studies on blood donors have identified
a few breakthrough cases of infection. These cases were mainly caused
HBV is a deoxyribonucleic acid (DNA) virus in the family Hepad- by HBV genotypes differing from that of the vaccine strain and were
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naviridae. The infectious virion is occasionally referred to as the Dane mild and self-limited. Such donations were not detected by HBsAg
particle and has surface and core components, surface antigen blood donation screening but required more sensitive HBV DNA
(HBsAg), and core antigen (HBcAg), respectively. Epitopes on the screening.
viral surface provide a basis for epidemiologic studies and consist of Some anti-HBc–positive and HBsAg-negative individuals have
the HBsAg “a,” d/y, and w/r determinants. However, this approach circulating HBV DNA, and this pattern defines so-called occult HBV
is being replaced by genotyping and DNA sequencing methods. infection (OBI). In rare cases, OBI may be accompanied by anti-
Recombinant vaccines containing the “a” determinant confer protec- HBs, usually at levels below 200 mIU per mL. Donors with OBI
tive immunity to a high proportion of vaccinees and are dramatically may transmit HBV via blood transfusion, but the frequency of such
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altering the incidence and prevalence of HBV infection in the general infection is low, and seems to be absent if anti-HBs is present.
population where they are in wide use and consequently also impact Although anti-HBs usually confers immunity to reinfection, sufficient
the frequency of HBV infection in the donor population. virus remains in the liver to transmit HBV following liver transplant
The average incubation period (the time from infection to liver from anti-HBs–positive donors through reactivation under intense
enzyme elevation and symptomatic hepatitis) is 59 days (range, 5 to immunosuppression.
12 weeks) but may be as long as 6 months. Symptoms, which occur Blood donors in the United States are currently queried for a
in 30% to 50% of infected persons age 5 years and older, include history of hepatitis and risks associated with hepatitis and screened
fatigue, anorexia, nausea, vomiting, jaundice, dark urine, light stools, for HBsAg, anti-HBc and HBV DNA. It should, however, be noted
arthralgias, rashes, vasculitis, and glomerulonephritis. The risk for that the FDA has eliminated the requirement to ask about a history
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progression to chronic infection is inversely related to age at infection. of viral hepatitis, effective May 2016. The detection of HBV DNA
HBV infection becomes chronic in more than 90% of infants, 25% is performed by nucleic acid testing (NAT) in minipools of 6–16
to 50% of children 1 to 5 years of age, and fewer than 5% of older donations each as now required per Food and Drug Administration
children and adults. Approximately 5% of the US population has (FDA) Guidance, Use of Nucleic Acid Tests on Pooled and Individual
serologic evidence of prior HBV infection (antibodies against HBcAg Samples from Donors of Whole Blood and Blood Components,
[anti-HBc] reactive). From the mid-1980s through 2013, with including Source Plasma, to Reduce the Risk of Transmission of
increasing immunization in early childhood, the incidence of acute Hepatitis B Virus (www.fda.gov/BiologicsBloodVaccines/Guidance
HBV infection has decreased. In 2013 41 states reported HBV infec- ComplianceRegulatoryInformation/Guidances/default.htm, October
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tions to the US Centers for Disease Control and Prevention (CDC) 2013) and made final in updates to the Code of Federal Regulations.
of which approximately 3000 were acute cases, or 1 case per 100,000 The risk for HBV transmission per unit in the United States has

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