Page 2039 - Hematology_ Basic Principles and Practice ( PDFDrive )

1810 Part XI Transfusion Medicine

infection, respectively. Thus most clinicians consider leukoreduction
and CMV seronegative blood to be equivalent; however, clinicians Other Herpesviruses (Herpes Simplex, Varicella-Zoster
caring for neonates are more likely to require serologic screening. Virus, Human Herpesviruses 6 and 7)
American Association of Blood Banks (AABB) recommends that each
institution review its internal policies for blood use in patients vulner- Infection with these viruses is very common to ubiquitous. From
able to CMV infection. Table 120.2 lists patient populations for 50% to 80% of the adult population is seroreactive to HSV-1 and/
whom use of “CMV risk–reduced” components, that is, CMV or HSV-2, up to 95% for VZV, more than 90% for HHV-6, and
seronegative, leukoreduced, or both, are thought to be beneficial. The 70% to 90% for HHV-7. Primary infection is followed by lifelong
failure of clinicians to recognize recipients requiring CMV-safe latency for all HHVs, and reactivation from latency is described for
transfusion and to request such components is an argument that has all. There is no credible evidence of transfusion transmission of HSVs
been advanced in support of universal prestorage (versus bedside) (causing orolabial and genital herpes and herpes encephalitis), VZV
leukoreduction. (chickenpox and shingles), or HHV-6 or HHV-7 (exanthem subitum
CMV DNA blood donation screening by NAT may be considered or roseola infantum, multiorgan dissemination with reactivation in
an additional risk reduction measure for donors with seronegative immunocompromised hosts).
window-period infections. However, current NAT assays would be Viremia occurs during both primary and reactivation infection
expected to be equivalent to serologic screening in detecting latently with HSV and VZV, but transmission by blood has never been
infected blood donors. Any consideration of additional testing is reported for these viruses. Although the lymphocyte association of
complicated by the absence of randomized studies using contempo- HHV-6 and HHV-7, like CMV and EBV, suggests the possibility of
rary leukoreduction methods and by our lack of understanding of the transfusion transmission, well-documented case reports or series are
clinical impact of transfusion-transmitted CMV in an era of CMV not available. Case reports of HHV-6 transmission by hematopoietic
monitoring and treatment. But with the advent of pathogen reduc- stem cells used molecular methods to detect integrated donor HHV-6
tion measures the need for any CMV donor screening will become DNA in engrafted donor cells and appear to represent transmission
obsolete. of latently infected cells rather than of active infection. Furthermore,
transplant recipients may reactivate preexisting latent infection,
thereby confounding the evaluation of potential transfusion transmis-
EPSTEIN-BARR VIRUS (HHV-4) sion. HHV-6 and HHV-7 are highly leukocyte associated after
primary infection, and leukoreduction would be expected to be effec-
EBV, a gammaherpesvirus, is the causative agent of heterophile tive by analogy to human CMV; however, cell-free viremia can be
antibody-positive infectious mononucleosis and is etiologically asso- found during primary infection.
ciated with Burkitt lymphoma, nasopharyngeal carcinoma, and
posttransplant lymphoproliferative disease. Transfusion transmission
of the virus is unusual because more than 90% of the adult popula- PARVOVIRUS
tion is infected, and second infection is prevented by host virus-
specific cytotoxic T-lymphocytes, capable of lysing EBV-infected B Human parvovirus B19 (erythrovirus) is a 19- to 23-nm–diameter
lymphocytes when viral peptides are expressed on the lymphocyte nonenveloped, single-stranded DNA virus from the family Parvoviri-
surface. Rare cases of transfusion-transmitted EBV presenting as dae, as are adeno-associated viruses, human parvovirus 4 (PARV4),
infectious mononucleosis have been described in immunocompetent PARV5, and bocaviruses. B19 has at least three genotypes. Genotype
recipients and in immunosuppressed patients following solid organ 1 infections appear predominantly in the United States and Europe.
transplantation. Aggressive EBV-associated lymphoproliferative dis- Genotype 2 infections appear confined to those born before 1973,
orders have been observed in patients with immune injury after cord and genotypes 3a and 3b infections occur in parts of West Africa.
blood stem cell transplantation but have not been documented fol- Infection with B19 is ubiquitous, with 50% of high school children
lowing transfusion. B lymphocytes are the likely source of transfusion- demonstrating seropositivity, increasing to 90% in older adults.
transmitted EBV infection, so leukoreduction is an attractive strategy Approximately three-quarters of transfusion recipients have B19 IgG
to prevent infection in transfusion recipients. Nonclinical studies antibodies. Natural transmission occurs through the respiratory route
suggest that leukoreduction is capable of removing detectable EBV most commonly and transplacentally to the fetus in up to 30% of
DNA from platelet concentrates and RBCs. women infected during pregnancy. Transfusion of blood and blood
components, plasma derivatives, and organ transplantation are minor
routes. In women infected during weeks 9 to 20 of pregnancy, fetal
Kaposi Sarcoma Herpesvirus (HHV-8) death occurs in 10% to 15% from hydrops fetalis. The low observed
incidence of infection in transfusion recipients results from prior
HHV-8 is a gammaherpes virus causally linked to Kaposi sarcoma, infection and immunity, co-infusion of neutralizing antibodies, and
primary effusion lymphoma, and multicentric Castleman disease. It is possibly because very high viral loads are uncommon in donor blood.
highly cell-associated with lymphocytes and monocyte-macrophages. Parvovirus B19 causes erythema infectiosum, or fifth disease,
Although generally spread person to person, including sexually, it has oligoarthritis, and neurologic and myocardial infections. Following
been shown to be transmitted by transplantation. There is convinc- acute infection, viral replication leads to extremely high-titer viremia
ing evidence of HHV-8 transmission by transfusion in sub-Saharan that declines at the time of IgM seroconversion approximately 9 days
Africa, where the seroprevalence of HHV-8 among blood donors is following infection. B19 may persist in bone marrow, liver, tonsils,
40%, and fresh, nonleukoreduced blood transfusions are commonly and skin of healthy persons with no recognized clinical significance,
used. The seroprevalence of HHV-8 among US blood donors has and low levels of B19 DNA have been amplified from the blood of
been reported to be as high as 20% to 25%, but a multicenter healthy people for several years after primary infection. The virus is
study using well-characterized antibody tests on donations from five highly tropic for erythroid progenitor cells using the P-blood group
representative US regions estimated a seroprevalence of only 3.5% antigen, or globoside, as its receptor, causing aplastic crises in patients
and showed no evidence of viremia by PCR. The possibility has with sickle cell anemia, other inherited hemolytic diseases, and condi-
been raised that transfusions in the United States have transmitted tions associated with decreased RBC survival, malaria, and HIV/
HHV-8, but subsequently reported studies comparing transfused AIDS. Acute infection impairs erythropoiesis for 7 to 10 days, with
patients with untransfused controls are not suggestive. Similar to complete cessation for 3 to 7 days, resulting in hemoglobin decreases.
what has been established for CMV infection, it is assumed that Persistent infection, causing red cell aplasia, occurs in those who fail
widespread leukoreduction in the United States mitigates the risk to develop neutralizing antibodies to the viral capsid protein 1. In
for HHV-8 transmission by transfusion, but this has not been these patients, the virus continues to circulate at high titer, greater
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proven. than 10 International Units (IU) or equivalent genome copies per